Phase II trial of oxaliplatin and gemcitabine in patients with malignant pleural or peritoneal mesothelioma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17133-17133 ◽  
Author(s):  
M. S. Boyar ◽  
M. Hesdorffer ◽  
R. N. Taub
Keyword(s):  
Partial Response ◽  
Phase Ii ◽  
Stable Disease ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Peritoneal Mesothelioma ◽  
Platinum Compound ◽  
Prior Chemotherapy ◽  
Gastrointestinal Dysmotility ◽  
Disease Stabilization

17133 Background: A prior phase II trial of oxaliplatin and gemcitabine in malignant pleural mesothelioma reported activity with a 40% partial response rate and stable disease in 24% of 25 previously untreated patients (Schutte W. et al., Clin Lung Cancer 2003;4:294). This trial was designed to further evaluate the efficacy of oxaliplatin and gemcitabine in patients with malignant pleural or peritoneal mesothelioma. Methods: Patients with histologically-confirmed malignant pleural or peritoneal mesothelioma not amenable to curative surgical treatment are eligible for enrollment on this single-institution phase II trial. One prior chemotherapy regimen is allowed, including pemetrexed with a platinum compound or gemcitabine. Presence of at least one radiologically-measurable lesion that has not been previously irradiated is required. Gemcitabine 1000 mg/m2 IV over 90 minutes is administered followed by oxaliplatin 100 mg/m2 IV over 2 hours on day 1 of a 14-day cycle. Treatment is continued for at least 6 cycles unless unacceptable toxicity or disease progression occurs. The primary outcome is to evaluate efficacy as measured by tumor response rate. The sequential two-stage design allows for enrollment of a total of 29 patients if 3 of 18 patients enrolled in the first stage have at least a partial response. Results: Ten eligible patients have been enrolled thus far and 6 are evaluable for response. Sites of disease include pleural (3) and peritoneal (3), and histologic subtypes are epithelioid (5) and sarcomatoid (1). Four patients had received prior chemotherapy. A total of 42 cycles have been given with a median of 8 cycles per patient. There are no partial or complete responses. Four patients have had stable disease for at least 4 months. Two patients with stable disease had received prior pemetrexed/gemcitabine or pemetrexed/cisplatin. Frequently observed toxicities include grade II fatigue, neuropathy and upper gastrointestinal dysmotility. Conclusion: This regimen of gemcitabine and oxaliplatin may provide disease stabilization in a subset of patients with malignant pleural and peritoneal mesothelioma, including those who have received prior chemotherapy. The regimen is well-tolerated. This study remains open to accrual. No significant financial relationships to disclose.

scholarly journals Phase II Trial of Sorafenib in Advanced Thyroid Cancer

2008 ◽  
Vol 26 (29) ◽  
pp. 4714-4719 ◽  
Author(s):  
Vandana Gupta-Abramson ◽  
Andrea B. Troxel ◽  
Anoma Nellore ◽  
Kanchan Puttaswamy ◽  
Maryann Redlinger ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Growth Factor ◽  
Partial Response ◽  
Thyroid Carcinoma ◽  
Phase Ii ◽  
Stable Disease ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Significant Advance ◽  
Open Label

PurposeGiven the molecular pathophysiology of thyroid cancer and the spectrum of kinases inhibited by sorafenib, including Raf kinase, vascular endothelial growth factor receptors, platelet-derived growth factor receptor, and RET tyrosine kinases, we conducted an open-label phase II trial to determine the efficacy of sorafenib in patients with advanced thyroid carcinoma.Patients and MethodsEligible patients with metastatic, iodine-refractory thyroid carcinoma received sorafenib 400 mg orally twice daily. Responses were measured radiographically every 2 to 3 months. The study end points included response rate, progression-free survival (PFS), and best response by Response Evaluation Criteria in Solid Tumors.ResultsThirty patients were entered onto the study and treated for a minimum of 16 weeks. Seven patients (23%; 95% CI, 0.10 to 0.42) had a partial response lasting 18+ to 84 weeks. Sixteen patients (53%; 95% CI, 0.34 to 0.72) had stable disease lasting 14 to 89+ weeks. Seventeen (95%) of 19 patients for whom serial thyroglobulin levels were available showed a marked and rapid response in thyroglobulin levels with a mean decrease of 70%. The median PFS was 79 weeks. Toxicity was consistent with other sorafenib trials, although a single patient died of liver failure that was likely treatment related.ConclusionSorafenib has clinically relevant antitumor activity in patients with metastatic, iodine-refractory thyroid carcinoma, with an overall clinical benefit rate (partial response + stable disease) of 77%, median PFS of 79 weeks, and an overall acceptable safety profile. These results represent a significant advance over chemotherapy in both response rate and PFS and support further investigation of this agent in these patients.

A randomized phase II trial comparing two doses of lenalidomide for the treatment of stage IV ocular melanoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20012-e20012 ◽  
Author(s):  
J. B. Zeldis ◽  
C. Heller ◽  
G. Seidel ◽  
N. Yuldasheva ◽  
D. Stirling ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stable Disease ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
Ocular Melanoma ◽  
Eligibility Criteria ◽  
Randomized Phase Ii ◽  
Animal Data ◽  
Disease Stabilization ◽  
Grade 3

e20012 Background: Ocular melanoma is the most common primary intraocular malignancy in adults with an incidence of 4.3 new cases per million. Approximately 50% of patients will develop metastases and the mean survival of those with liver metastases is 8–10 months. There are no effective systemic therapies. Pre-clinical studies of the antiangiogenic and immunomodulatory agent, lenalidomide, have shown promise in animal models of human ocular melanoma. We therefore conducted a phase II trial comparing two doses of oral lenalidomide. Methods: Patients with stage IV ocular melanoma, who met eligibility criteria and demonstrated disease progression, were enrolled on an IRB approved prospective random assignment trial comparing 5 mg and 25 mg of lenalidomide administered once a day orally for 21 days with a 7 day recovery (one cycle). Lesions were measured at baseline and every 3 months and scored for response by RECIST criteria. Patients who completed 3 cycles were eligible for response evaluation. Patients with responding lesions or with stable disease could continue receiving the agent. Toxicity was assessed using the NCI Common Toxicity Criteria. Results: Seventeen patients (13 female, 4 male; mean age 53) met eligibility criteria and were randomized to 5 mg (9 patients) or 25 mg (8 patients) of lenalidomide. The agent was well tolerated at both doses with only three grade 3 toxicities (two decreased ANC and one rash/puritis) requiring dose adjustments. Sixteen patients were eligible for response assessments. Nine patients had progressive disease by RECIST criteria following 3 cycles of therapy. Seven patients (44%) had stable disease for a mean of 7 months (range 6–12 months). There were no RECIST defined responders. There were no differences between the two dose groups with respect to toxicity or disease stabilization. Conclusions: Lenalidomide is well tolerated at doses of 5 mg and 25 mg orally for a 21 day cycle by patients with stage IV ocular melanoma. While no responses were seen, disease stabilization for a mean of 7 months was seen in 44% of patients. This effect was consistent with the pre-clinical animal data. Based on these results, further development of lenalidomide in combination with other agents should be considered for the treatment of metastatic ocular melanoma. [Table: see text]

Randomized phase II trial of MIBG versus MIBG/vincristine/irinotecan versus MIBG/vorinostat for relapsed/refractory neuroblastoma: A report from the New Approaches to Neuroblastoma Therapy Consortium.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10500-10500
Author(s):  
Steven G. DuBois ◽  
Meaghan Granger ◽  
Susan G. Groshen ◽  
Denice Tsao-Wei ◽  
Anasheh Shamirian ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Response Rates ◽  
Response Criteria ◽  
Current Response ◽  
Minor Response ◽  
Randomized Phase Ii ◽  
Grade 3

10500 Background: 131I-metaiodobenzylguanidine (MIBG) remains one of the most active agents for neuroblastoma. It is not clear if putative radiation sensitizers improve upon this activity. The primary aim of this trial was to identify the MIBG treatment regimen with highest response rate among: MIBG monotherapy (Arm A); MIBG/Vincristine/Irinotecan (Arm B); MIBG/Vorinostat (Arm C). The secondary aim was to compare toxicity across arms. Methods: We conducted a multicenter, randomized phase II trial. Patients 1-30 years with relapsed/refractory high-risk neuroblastoma were eligible with at least one MIBG-avid site and adequate autologous stem cells (ASCs). All patients received MIBG 18 mCi/kg on Day 1 and ASC on day 15. Patients on Arm A received only MIBG; patients on Arm B also received vincristine (2 mg/m2) IV on Day 0 and irinotecan (50 mg/m2) IV daily on Days 0-4; patients on Arm C also received vorinostat (180 mg/m2) orally once daily on days -1 to 12. The primary endpoint was response after one course according to NANT response criteria. The trial was designed as a pick-the-winner study with a maximum of 105 eligible and evaluable patients to ensure an 80% chance that the arm with highest response rate is selected, if that response rate is at least 15% higher than the other arms. Results: 114 patients enrolled. Three patients were ineligible and 6 eligible patients never received MIBG, leaving 105 eligible and evaluable patients (36 Arm A; 35 Arm B; and 34 Arm C; 55 boys; median age 6.5 years). 9 patients had received prior MIBG monotherapy, 65 prior irinotecan, and 7 prior vorinostat. After one course, the response rates (Partial Response or better) on Arms A, B, and C were 17% (95% CI 7-33%), 14% (5-31%), and 32% (18-51%). An additional 4, 4, and 7 patients met NANT Minor Response criteria [partial response in one disease category (e.g., bone marrow) and stable disease in other categories] on Arms A, B, and C, respectively. On Arms A, B, and C, rates of any grade 3+ non-hematologic toxicity were 19%, 49% and 32%; rates of grade 3+ diarrhea were 0%, 11%, 0%; and rates of grade 3+ febrile neutropenia were 6%, 11%, and 0%. Conclusions: The combination of vorinostat/MIBG had the highest response rate, with manageable toxicity. Vincristine and irinotecan do not improve the response rate to MIBG and are associated with increased toxicity. These data provide response rates for MIBG monotherapy in a contemporary patient population assessed with current response criteria. Clinical trial information: NCT02035137.

Phase II Trial of Pulse Dosed Lenalidomide In Previously Treated Chronic Lymphocytic Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1383-1383 ◽  
Author(s):  
Georg Aue ◽  
Susan Soto ◽  
Janet Valdez ◽  
Diane C Arthur ◽  
Xin Tian ◽  
...  
Keyword(s):  
Side Effects ◽  
Chronic Lymphocytic Leukemia ◽  
Partial Response ◽  
Phase Ii ◽  
Stable Disease ◽  
Phase Ii Trial ◽  
Lymphocytic Leukemia ◽  
Bulky Disease ◽  
Starting Dose ◽  
Duration Of Response

Abstract Abstract 1383 Introduction: Lenalidomide (L) has activity in relapsed chronic lymphocytic leukemia (CLL). The mechanism of action is not well understood but may involve stimulation of anti-leukemic immune responses. Myelosuppression especially neutropenia is a concerning side effect. We reasoned that pulsed dosing of lenalidomide could reduce myelosuppression while maintaining the immune stimulatory effect. To test this concept we initiated a single center, phase II trial (ClinicalTrials.gov Identifier: NCT00465127) of lenalidomide given in cycles of 3 weeks on, 3 weeks off drug (42 day cycles). Methods: Patients (pts) with relapsed CLL or small lymphocytic lymphoma with ANC>500/ul and platelets >20,000/ul were eligible. The primary endpoint defined as response after 4 cycles has been recorded for all participants. Pts with partial response were allowed to receive up to 4 additional cycles. The starting dose for the first 10 pts was 20 mg daily; the starting dose for pt 11 onwards was lowered to 10 mg daily because of toxicities observed in other L trials for CLL. TLS prophylaxis with Allopurinol was mandated during cycle 1–3. Deep venous thrombosis (DVT) prophylaxis was not mandated unless risk factors were present. Ibuprofen and corticosteroids were allowed to treat symptoms of a cytokine release syndrome (CRS, defined by LN swelling, fever, fatigue, pain, chills, dehydration). Responses were assessed by IWCLL criteria and included CT scanning. Patient characteristics (n=33) were: median age 64 years (36-78); median number of prior therapies 3 (range 1–7); 52% Rai stage III-IV; 70% bulky disease; 30% fludarabine refractory; 56% (of 27 pts) ZAP70 pos; 64% (of 25 pts) unmutated immune globulin VH mutation status; 43% del 17p; 15% del 11q. Results: A total of 131 cycles of L were given. 31 pts received at least 2 cycles of therapy (range 2–8) and were evaluable for response: 5 (16%) partial response (PR), 18 (58%) stable disease, and 8 (26%) progressive disease. 4 of 5 responding pts had del 17p and bulky disease. In responders (n=5, PR) vs non responders (n=26, SD+PD) the PFS was 16 vs 6 months (p>0.01), and the time to next therapy was 17 vs 6 months (p>0.01), respectively. Once treatment was stopped, duration of response was short lived (median 6 months, range 2–18). 4 out of 5 responders were observed in the 20 mg dose starting group versus only 1 responder in the 10 mg group (p=0.03). There was no difference in the CRS score between the 2 groups (2.5 vs 1.5, p=0.17). Hematologic responses were observed in 11 out of 24 CLL pts (45%). At the completion of 4 cycles CD4 and CD8 counts increased by 20%, while NK cell counts remained unchanged. Dose modifications/withdrawl: 41% of cycles required dose adjustments prior to or during cycles 1–4. 9 pts (27%) did not complete 4 cycles of L because of: autoimmune cytopenias (2 pts), side effects (4 pts; CRS 1 pt, neutropenia 3 pts), withdrawal from study (2 pts), and disease progression (1 pt). Toxicity: Gr 3/4 neutropenia was observed in 56% of 131 cycles, often worsening with cumulative cycles. Gr 3/4 thombocytopenia and anemia were seen in 30% and 15% of cycles, respectively. Gr 1/2 and 3/4 infections occurred in 23% and 11% of cycles, respectively, 8 of those in the setting of neutropenia. Gr 3 CMV colitis, PCP pneumonia and Candedemia each were observed once. 1 patient died from streptococcal sepsis in cycle 4. Gr 1/2 and 3/4 CRS were observed in 43% and 10% of cycles, respectively. A CRS was encountered in 78% of first cycles typically within the first week, and in 48%, 38% and 30% of cycles 2–4, respectively. 6 DVTs (Gr 3) were diagnosed in 5 pts. Other common side effects were fatigue (62%), rash (39%) and muscle cramps (27%), all Gr 1/2. No case of tumor lysis syndrome was seen. Conclusion: L cycled 3 weeks on, 3 weeks off led to stable disease in the majority of pts and induced PRs in 16% of relapsed CLL patients with high risk disease. Pulse dosing of L did not lead to reduced toxicities. Myelosuppression and infections remain a major concern. 4 out of 5 responders were observed in the 20 mg cohort arguing for higher L starting doses. Notably, side effects, particularly the CRS, were similar in the two cohorts. Once L was discontinued, the duration of response was short, suggesting a need for continued therapy in pts who are able to tolerate the drug. Disclosures: Off Label Use: Lenalidomide is not FDA approved in Chronic Lymphocytic leukemia.

A Prospective Multicenter Phase II Trial of Pentostatin in Adult Patients with Steroid-Refractory Chronic Graft-Versus-Host Disease (cGvHD): A Cancer and Leukemia Group B/Eastern Cooperative Oncology Group Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2238-2238
Author(s):  
Sherif Farag ◽  
Kouros Owzar ◽  
Vera Hars ◽  
Hillard M. Lazarus ◽  
Edward A. Stadtmauer ◽  
...  
Keyword(s):  
Partial Response ◽  
Corticosteroid Therapy ◽  
Phase Ii ◽  
Graft Versus Host Disease ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Hematological Toxicity ◽  
Graft Versus Host ◽  
Grade 3 ◽  
Steroid Refractory

Abstract Abstract 2238 Poster Board II-215 Chronic graft-versus-host disease is the most common late complication occurring following allogeneic transplantation, and is the principal cause of late morbidity and non-relapse mortality. Corticosteroids remain the cornerstone of primary treatment for cGvHD with about half of patients responding. Patients who fail to respond to initial corticosteroid therapy, however, have a poor outcome with no standard approach uniformly accepted. Pentostatin is a purine nucleoside analogue that irreversibly inhibits adenosine deaminase, with accumulation of dATP, causing apoptosis of lymphocytes, and holds promise for the management of acute and cGvHD. We conducted a multi-institutional, prospective phase II trial to evaluate the response rate (RR) of pentostatin in patients with steroid-refractory cGvHD. In a two-stage design with both types I and II errors set at 0.1, we hypothesized that pentostatin would produce a response rate (complete response + partial response) of 40% or more, with less than 20% being unaccpetable. Patients were eligible if they were >18 years old, had a Karnofsky performance status (KPS) of >30%, histologically-proven extensive stage cGvHD that was refractory to corticosteroids defined as progression of disease despite at least 2 weeks of treatment with 1 mg/kg/day of prednisone or equivalent, no response or minor response to at least 4 weeks of 1 mg/kg/day prednisone (or equivalent), or who achieved only a partial response after 8 weeks of corticosteroid therapy. Response was assessed using the Hopkins scoring system as previously reported (Jacobsohn et al. J Clin Oncol, 25:4255-61, 2007). Pentostatin was administered at a dose of 4 mg/m2 IV every 2 weeks for a maximum of 12 doses. From March 2004 to March 2007, 38 patients with median age 46.5 (27-66) years and median KPS 70% (40%-90%) were treated with pentostatin. cGvHD followed transplantation from matched related donors in 29 and unrelated donors in 9 patients. Thirty-three patients had progressive onset cGvHD, while onset was quiescent in 2, and de novo in 3 patients. The median time from onset of cGvHD to start of study treatment was 416 (26-2,813) days, and the median number of prior lines of therapy for cGvHD was 3 (range, 1-6). cGvHD involved skin (n=35) with scleroderma present in 21 patients, oral mucosa (n=24), liver (n=9), gut (n=4), and lung (n=2). Thirty-five patients were evaluable for response; 2 patients died after 6 and 7 days of treatment, respectively, due to sepsis, and data was incomplete in 1 patient who committed suicide after 3 cycles. Of 35 patients evaluable for response, there were 2 complete responses (CR), 5 partial responses (PR) for a total response rate of 20%. If minor responses (in 7 patients) are also considered, then 14 of 35 (40%) had an objective improvement in cGvHD. Six patients had stable disease, 1 a mixed response, and 14 patients progressed on therapy. Of 34 patients evaluable for toxicity, grade 3-4 hematological toxicity included neutropenia (n=4), thrombocytopenia (n=3), and anemia (n=1). Grade 3-4 clinically significant non-hematological toxicity that was at least possibly related to pentostatin included fatigue (n=3), renal failure (n=3), anorexia (n=2), infection (n=9), CNS hemorrhage (n=1), and rash (n=1). Thirteen patients died on study; causes of death were infection (n=6), cGvHD progression (n=3), and unrelated causes (n=3). The 1-year and 2-year progression-free survival (for GvHD) for all patients treated on study were 32% (95% CI: 18%-46%) and 24% (95% CI: 12%-38%), respectively. The 1-year and 2-year overall survival was 53% (95% CI: 38%-60%) and 50% (95% CI: 33%-65%), respectively. We conclude that pentostatin is an active agent in patients with steroid-refractory chronic GvHD but should be investigated further in cGvHD patients in an earlier course of their disease where a greater impact on long-term outcome may be observed. Disclosures: No relevant conflicts of interest to declare.

Bendamustine Combined With Rituximab in Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia: A Multicenter Phase II Trial of the German Chronic Lymphocytic Leukemia Study Group

2011 ◽  
Vol 29 (26) ◽  
pp. 3559-3566 ◽  
Author(s):  
Kirsten Fischer ◽  
Paula Cramer ◽  
Raymonde Busch ◽  
Stephan Stilgenbauer ◽  
Jasmin Bahlo ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Partial Response ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Refractory Disease ◽  
Overall Response

Purpose The objective of this trial was to evaluate safety and efficacy of bendamustine combined with rituximab (BR) in patients with relapsed and/or refractory chronic lymphocytic leukemia (CLL). Patients and Methods Seventy-eight patients, including 22 patients with fludarabine-refractory disease (28.2%) and 14 patients (17.9%) with deletion of 17p, received BR chemoimmunotherapy. Bendamustine was administered at a dose of 70 mg/m2 on days 1 and 2 combined with rituximab 375 mg/m2 on day 0 of the first course and 500 mg/m2 on day 1 during subsequent courses for up to six courses. Results On the basis of intent-to-treat analysis, the overall response rate was 59.0% (95% CI, 47.3% to 70.0%). Complete response, partial response, and nodular partial response were achieved in 9.0%, 47.4%, and 2.6% of patients, respectively. Overall response rate was 45.5% in fludarabine-refractory patients and 60.5% in fludarabine-sensitive patients. Among genetic subgroups, 92.3% of patients with del(11q), 100% with trisomy 12, 7.1% with del(17p), and 58.7% with unmutated IGHV status responded to treatment. After a median follow-up time of 24 months, the median event-free survival was 14.7 months. Severe infections occurred in 12.8% of patients. Grade 3 or 4 neutropenia, thrombocytopenia, and anemia were documented in 23.1%, 28.2%, and 16.6% of patients, respectively. Conclusion Chemoimmunotherapy with BR is effective and safe in patients with relapsed CLL and has notable activity in fludarabine-refractory disease. Major but tolerable toxicities were myelosuppression and infections. These promising results encouraged us to initiate a further phase II trial evaluating the BR regimen in patients with previously untreated CLL.

scholarly journals Efficacy of Elotuzumab Based Combinations in Patients with Multiple Myeloma - a Systematic Review

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5548-5548
Author(s):  
Arafat Ali Farooqui ◽  
Ahmad Anjum ◽  
Muhammad Saad Farooqi ◽  
Talha Bin Farooq ◽  
Tanveer Shaukat ◽  
...  
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Partial Response ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Entire Study ◽  
Tract Infections

Introduction Multiple myeloma afflicted cells express signaling lymphocytic activation molecule family member 7 (SLAMF7). Elotuzumab; a monoclonal antibody (mAb), targets SLAMF7 and fights myeloma cells by stimulating phagocytic action of natural killer (NK) cells and via antibody‐dependent cell‐mediated cytotoxicity (ADCC) pathway. This study focuses on the clinical utility and tolerability of elotuzumab based combinations in patients (pts) with multiple myeloma (MM). Methods Literature search of PubMed, Embase, Clinicaltrials.gov, Cochrane and Web of Science was performed from inception to June 12, 2019 for elotuzumab based combinations in MM patients. Total of 06 phase II and phase III clinical trials were selected for systematic review out of 292 studies. Results Elotuzumab (E) based combinations were evaluated in 1075 patients (pts) out of 1115 enrolled pts. 119 were newly diagnosed (ND) and 956 were relapsed/refractory (RR) patients. Newly Diagnosed MM patients: Takezako et al. 2017; in phase II trial, showed overall response rate (ORR) of 88% (complete response [CR] 3% + stringent CR [sCR] 5% + partial response [PR] 43% + very good partial response [VGPR] 38%) with ELd (E-Lenalidomide-dexamethasone) arm vs 74% in Ld arm in 82 ND pts. Progression free survival (PFS) at 1 year (y) was 93% versus (vs) 91%. Grade (G) ≥3 adverse events (AEs) included neutropenia (18%) and leukopenia (15%). Relapsed/Refractory MM patients: E-Bortezomib(B)-d arm in a phase II trial by Jakubowiak et al. (2016) showed 1 y PFS of 39% vs 33% in Bd arm in 152 RR pts (Hazard ratio [HR]: 0.72; p = .09) with 28% decrease in progression or death with EBd vs Bd arm. Objective response rate (ORR) was 66% (4% CR+ 33% VGPR + 30% PR) vs 63%. OS (overall survival) at 1 y was 85% (EBd) and 74% (Bd) (HR: 0.6). G≥3 AEs were infections (21%), thrombocytopenia and peripheral neuropathy (9% each). Mateos et al. (2016) in phase II trial (n=40) evaluated E-T (thalidomide)-d with or without Cy (cyclophosphamide) in heavily pre-treated RR pts. Pts received Cy if they failed to achieve PR by the 5th cycle or because of progressive disease (PD). Responses were better with ETd vs ETdCy. ORR was 38% (95% CI: 23-54) in ETd vs 9% (95% CI: 0-41) in ETdCy. Entire study yielded median PFS (mPFS) of 3.9 months (mo) (95% CI: 2.79%-9.43%) with 1-y PFS of 30% and mOS of 16.3 mo (95% Cl: 8.87%-25.66%) with 1-y survival rate of 63%. G≥3 AEs were lymphopenia (50%), anemia (20%), leucopenia (20%) and respiratory tract infections (RTI) (8%). Dimopoulos et al. 2018 studied E + pomalidomide (P) + d (EPd) for RR pts with ≥2 prior therapies in phase II ELOQUENT-3 trial (n=117). EPd arm yielded mPFS of 10.2 mo vs 4.6 mo in Pd arm [HR: 0.54 (95% CI: 0.34-0.86; p=0.008)], i.e. 46% lower risk of progression or death in EPd vs Pd arm. ORR was 53% (CR 5% + sCR 3% + PR 33% + VGPR 12%) in EPd vs 26% in Pd arm (odds ratio [OR]: 3.25 (1.49-7.11). G≥3 AEs were anemia (10%), neutropenia and infections (13% each). Phase III ELOQUENT-2 trial randomized 646 RR pts. PFS at 4 y was 21% vs 14% (HR: 0.71, 95% CI: 0.59-0.86; p= .0004), favoring ELd with 29% reduction in myeloma progression or death. With VGPR of 30%, ORR was 79% vs 66 % (ELd vs Ld) with HR: 0.77; 95% CI: 0.62-0.95; p = 0.0176. OS at 4 y was 50% vs 43% (HR: 0.78; 95% CI: 0.63-0.96). G≥3 AEs included lymphocytopenia (79%), neutropenia (36%), anemia (20%) and thrombocytopenia (21%). (Dimopoulos et al, 2018). Newly Diagnosed & Relapsed/Refractory MM patients: Phase II trial (n=70) by Berenson et al. (2017) studied G≥3 infusion reactions (IRs) using ELd in ND (n=37) and RR (n=33) pts. ORR was 78% (95% CI: 62%‐90%) for ND and 61% (95% CI: 42%‐77%) for RR pts. Other response rates were CR 6%, VGPR 27% and PR 37% in all patients. G3 AEs included anemia in 10% pts (no G3 IRs were seen). Conclusion: Elotuzumab based combinations showing promising outcomes in terms of ORR, PFS and OS for ND and RR MM patients with tolerable toxicity profile. More clinical studies with elotuzumab in unique and newer combinations need to be tested in prospective trials. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Phase II trial of robotic stereotactic radiosurgery (SBRT) in patients with recurrent gynecologic malignancies.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5102-5102
Author(s):  
Charles Kunos ◽  
James Brindle ◽  
Ramon Adams ◽  
Robert DeBernardo
Keyword(s):  
Partial Response ◽  
Phase Ii ◽  
Stable Disease ◽  
Clinical Benefit ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Case Series ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Benefit Rate

5102 Background: Ablative radiation dose delivered by a robotic SBRT platform has shown progression-free survival benefit in two limited case series among patients with recurrent gynecological malignancies. The therapeutic impact of SBRT on disease progression (PD) was evaluated in the recurrent setting in this phase II trial. Methods: Fifty patients with recurrent and measurable gynecologic malignancy were treated with SBRT. The cohort included patients with recurrent ovarian (n =25), endometrial (n =14), cervical (n =9), or vulvar (n =2) cancer, 1 prior chemotherapy or radiation regimen, and GOG performance status 0, 1, 2. Patients underwent image-guided SBRT in 3 daily doses of 800 cGy = 2400 cGy. SBRT planning target volumes were determined by both the radiation and gynecologic oncologist using non-contrasted CT and 18F-FDG PET/CT overlays. The primary endpoints were 6-month clinical benefit rate (# complete response + # partial response + # stable disease without PD [by RECIST v1.0] / 50), and less than 30-day posttherapy toxicity. Results: Between July 2009 and September 2011, 50 patients were enrolled and have a median posttherapy follow-up of 9 months. At 3 months, 50% (n=25) had complete response, 46% (n=23) had partial response, and 4% (n=2) had stable disease in SBRT-targeted lesions. Twenty-six patients (52%) have had non-SBRT target PD and 18 (36%) have died of PD. Of the 50 patients, 33 had a PD-free interval of at least 6 months, for an overall clinical benefit rate of 66%. Less than 30-day posttherapy SBRT-related toxicities were grade 2 fatigue (n =9 [18%]), grade 2 nausea (n =3[6%], grade 3 nephropathy (n =2[4%]), and grade 4 hyperbilirubinemia (n =1[2%]). Conclusions: This is the first phase II clinical trial of SBRT showing a clinically relevant benefit of ablative radiation in the setting of recurrent gynecological disease. Despite excellent control of targeted lesions with minimal toxicity, non-SBRT target PD rates are high, spurring interest for future SBRT-chemotherapy clinical trials.

scholarly journals NF106: A Neurofibromatosis Clinical Trials Consortium Phase II Trial of the MEK Inhibitor Mirdametinib (PD-0325901) in Adolescents and Adults With NF1-Related Plexiform Neurofibromas

2021 ◽  
Vol 39 (7) ◽  
pp. 797-806
Author(s):  
Brian D. Weiss ◽  
Pamela L. Wolters ◽  
Scott R. Plotkin ◽  
Brigitte C. Widemann ◽  
James H. Tonsgard ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase Ii ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Maximum Dose ◽  
Significant Morbidity ◽  
Plexiform Neurofibromas ◽  
Patient Reported ◽  
Erk Kinase

PURPOSE Patients with neurofibromatosis type 1 (NF1) frequently develop plexiform neurofibromas (PNs), which can cause significant morbidity. We performed a phase II trial of the MAPK/ERK kinase inhibitor, mirdametinib (PD-0325901), in patients with NF1 and inoperable PNs. The primary objective was response rate based on volumetric magnetic resonance imaging analysis. METHODS Inclusion criteria included age ≥ 16 years and a PN that was either progressive or causing significant morbidity. First-dose pharmacokinetics were performed. Patients completed patient-reported outcome measures. Patients received mirdametinib by mouth twice a day at 2 mg/m2/dose (maximum dose = 4 mg twice a day) in a 3-week on/1-week off sequence. Each course was 4 weeks in duration. Evaluations were performed after four courses for the first year and then after every six courses. Patients could receive a maximum of 24 total courses. RESULTS Nineteen patients were enrolled, and all 19 received mirdametinib. The median age was 24 years (range, 16-39 years); the median baseline tumor volume was 363.8 mL (range, 3.9-5,161 mL). Eight of the 19 patients (42%) achieved a partial response of the target PN by course 12, and 10 (53%) had stable disease. One patient (5%) developed progressive disease at course 8. Significant and durable decreases were observed in pain ratings. CONCLUSION To our knowledge, this analysis represents the first characterization of the activity and pharmacokinetics of mirdametinib in patients with NF1 and PNs and is the first published response study for MAPK/ERK kinase inhibitors in adults with NF1 and PNs. Mirdametinib given at 2 mg/m2/dose (maximum dose, 4 mg) twice daily in a 3-week on/1-week off sequence resulted in a 42% partial response rate with preliminary evidence of reduction in pain.

Phase II Trial of 4′-Epi-Doxorubicin in Locally Advanced or Metastatic Gastric Cancer

1988 ◽  
Vol 74 (3) ◽  
pp. 313-315 ◽  
Author(s):  
Eduardo Cazap ◽  
Roberto Estevez ◽  
Mario Bruno ◽  
Daniel Levy ◽  
Carlos Algamiz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Adenocarcinoma ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Metastatic Gastric Cancer ◽  
Phase Iii ◽  
Future Studies ◽  
Phase Iii Trials

Patients with locally advanced or metastatic gastric adenocarcinoma received an i.v. bolus of 4′-epi-doxorubicin, 75/mg/m2/cycle, every 21 days. Partial responses were observed in 5 of 23 evaluable patients (21.7%). Treatment was generally well tolerated and toxicity was mild. The response rate to epirubicin appears to be very similar to that reported for doxorubicin. Larger doses of epirubicin could be safely used in future studies, and further evaluation of epirubicin in phase III trials is indicated.

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