A multicenter phase II study of thalidomide in combination with interleukin-2 (IL-2) in patients with previously untreated metastatic renal cell carcinoma (MRCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14636-14636 ◽  
Author(s):  
D. Farray ◽  
J. I. Clark ◽  
T. Kuzel ◽  
J. P. Dutcher
Keyword(s):  
Phase Ii ◽  
Low Dose ◽  
Group Performance ◽  
Clear Cell ◽  
Phase Ii Study ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Interleukin 2 ◽  
Open Label ◽  
Anti Tumor Activity

14636 Background: Thalidomide, a drug with immune modulating and anti-angiogenic properties has shown activity in relapsed/refractory MRCC; furthermore, early phase I data of oral thalidomide with subcutaneous low-dose IL-2 showed the combination to be safe. The potential anti-tumor activity of this combination formed the basis of this study. Methods: The aim of this multi-center, open label, phase II study was to determine the efficacy and safety of thalidomide and IL-2 given in combination. Patients (pts) with untreated clear cell MRCC with measurable disease and previous nephrectomy were eligible. Two 6-week cycles of thalidomide and IL-2 were planned. Each cycle consisted of thalidomide started at 200 mg orally daily and titrated to 400 mg daily on the 4th day for 6 weeks; IL-2 was started one week post initiation of thalidomide at a dose of 7mIU/m2 subcutaneously days 1–5 for 4 weeks, followed by 2 weeks off therapy. Therapy was to be continued until progression, if there was at least stable disease (SD). Planned accrual was 53 patients. Results: 11 pts were enrolled. The trial was terminated early due to lack of responses. Median age was 57 years (51–66). All pts had an Eastern Cooperative Oncology Group performance status of 2 or better. The only grade 3 toxicities were fatigue (3 pts), neuropathy (1 pt), anorexia (1 pt), dyspnea (1 pt), edema (1 pt); these required dose reductions as per protocol. There were no objective responses: 3 pts had SD, 8 pts had progressive disease (PD). The 3 pts with SD completed 4, 4, and 6 cycles of therapy respectively; of the 8 pts with PD, 3 completed two cycles, and 5 completed one cycle of therapy. Conclusions: The combination of thalidomide and low-dose IL-2 was well tolerated, but in this trial did not show anti-tumor activity in patients with clear cell MRCC. We thank Celgene for support of this trial. No significant financial relationships to disclose.

scholarly journals Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation

2020 ◽  
Vol 38 (13) ◽  
pp. 1378-1388 ◽  
Author(s):  
Eileen M. O’Reilly ◽  
Jonathan W. Lee ◽  
Mark Zalupski ◽  
Marinela Capanu ◽  
Jennifer Park ◽  
...  
Keyword(s):  
Phase Ii ◽  
Group Performance ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
High Response Rate ◽  
Open Label ◽  
Free Survival ◽  
Palb2 Mutation

PURPOSE Five percent to 9% of pancreatic ductal adenocarcinomas (PDACs) develop in patients with a germline BRCA1/2 or PALB2 (g BRCA/PALB2+) mutation. Phase IB data from a trial that used cisplatin, gemcitabine, and veliparib treatment demonstrated a high response rate (RR), disease control rate (DCR), and overall survival (OS) in this population. We designed an open-label, randomized, multicenter, two-arm phase II trial to investigate cisplatin and gemcitabine with or without veliparib in g BRCA/PALB2+ PDAC. PATIENTS AND METHODS Eligible patients had untreated g BRCA/PALB2+ PDAC with measurable stage III to IV disease and Eastern Cooperative Oncology Group performance status of 0 to 1. Treatment for patients in arm A consisted of cisplatin 25 mg/m2 and gemcitabine 600 mg/m2 intravenously on days 3 and 10; treatment for patients in arm B was the same as that for patients in arm A, and arm A also received veliparib 80 mg orally twice per day on days 1 to 12 cycled every 3 weeks. The primary end point was RRs of arm A and arm B evaluated separately using a Simon two-stage design. Secondary end points were progression-free survival, DCR, OS, safety, and correlative analyses. RESULTS Fifty patients were evaluated by modified intention-to-treat analysis. The RR for arm A was 74.1% and 65.2% for arm B ( P = .55); both arms exceeded the prespecified activity threshold. DCR was 100% for arm A and 78.3% for arm B ( P = .02). Median progression-free survival was 10.1 months for arm A (95% CI, 6.7 to 11.5 months) and 9.7 months for arm B (95% CI, 4.2 to 13.6 months; P = .73). Median OS for arm A was 15.5 months (95% CI, 12.2 to 24.3 months) and 16.4 months for arm B (95% CI, 11.7 to 23.4 months; P = .6). Two-year OS rate for the entire cohort was 30.6% (95% CI, 17.8% to 44.4%), and 3-year OS rate was 17.8% (95% CI, 8.1% to 30.7%). Grade 3 to 4 hematologic toxicities for arm A versus arm B were 13 (48%) versus seven (30%) for neutropenia, 15 (55%) versus two (9%) for thrombocytopenia, and 14 (52%) versus eight (35%) for anemia. CONCLUSION Cisplatin and gemcitabine is an effective regimen in advanced g BRCA/PALB2+ PDAC. Concurrent veliparib did not improve RR. These data establish cisplatin and gemcitabine as a standard approach in g BRCA/ PALB2+ PDAC.

scholarly journals Phase II Study of Sorafenib in Combination With Docetaxel and Cisplatin in the Treatment of Metastatic or Advanced Gastric and Gastroesophageal Junction Adenocarcinoma: ECOG 5203

2010 ◽  
Vol 28 (18) ◽  
pp. 2947-2951 ◽  
Author(s):  
Weijing Sun ◽  
Mark Powell ◽  
Peter J. O'Dwyer ◽  
Paul Catalano ◽  
Rafat H. Ansari ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Phase Ii ◽  
Group Performance ◽  
Phase Ii Study ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Free Survival

Purpose The combination of sorafenib with chemotherapy is well-tolerated and is associated with encouraging response rates in several malignances. Both docetaxel and cisplatin are active in gastric cancer. A phase II study was conducted to determine the efficacy and toxicity of combined sorafenib, docetaxel, and cisplatin in patients with metastatic or advanced adenocarcinoma of stomach or gastroesophageal junction (GEJ). Patients and Methods Forty-four chemotherapy-naïve patients with Eastern Cooperative Oncology Group performance status 0 or 1, of whom 80% had metastatic disease and two thirds had poorly differentiated gastric or GEJ adenocarcinoma, were enrolled. The treatment regimen was sorafenib 400 mg orally twice a day for 21 days, docetaxel 75 mg/m2 intravenously on day 1, and cisplatin 75 mg/m2 intravenously on day 1, repeated every 21 days. The primary end point was response rate to the combination. Toxicity, overall survival, and progression-free survival were assessed as secondary end points. Results Eighteen of the 44 eligible and treated patients showed partial responses (41%; 90% CI, 28% to 54%). The median progression-free survival was 5.8 months (90% CI, 5.4 to 7.4 months). The median overall survival was 13.6 months (90% CI, 8.6 to 16.1 month). The major toxicity of this regimen was neutropenia, which reached grade 3 to 4 in 64% of patients. One patient experienced hemorrhage at the tumor site. Conclusion The combination of sorafenib, docetaxel, and cisplatin has an encouraging efficacy profile with tolerable toxicity. Additional studies of sorafenib with chemotherapy are warranted in gastric cancer.

A phase III study of nivolumab (NIVO), NIVO + ipilimumab (IPI), or chemotherapy (CT) for microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC): Checkmate 8HW.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS266-TPS266 ◽  
Author(s):  
Sandzhar Abdullaev ◽  
Thierry André ◽  
Ming Lei ◽  
Heinz-Josef Lenz ◽  
James Novotny ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Low Dose ◽  
Group Performance ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Open Label ◽  
Phase 3

TPS266 Background: Patients (pts) with MSI-H/dMMR mCRC treated with CT have poorer outcomes than pts with microsatellite stable/MMR proficient mCRC. NIVO (anti–programmed death [PD]-1) and IPI (anti–cytotoxic T lymphocyte antigen-4 [CTLA-4]) are immune checkpoint inhibitors that act synergistically and promote antitumor immune response by complementary mechanisms. NIVO±IPI received accelerated US FDA approval for MSI-H/dMMR mCRC that progressed after fluoropyrimidine, oxaliplatin, and irinotecan treatment based on the phase 2, non-randomized, multicohort CheckMate 142 study. Indirect comparisons suggest that NIVO (3 mg/kg) + low-dose IPI (1 mg/kg) provides improved clinical benefit vs NIVO (investigator-assessed [INV] objective response rate [ORR] 55% vs 31%; 12-month [mo] INV progression-free survival [PFS] rate 71% vs 50%; 12-mo overall survival [OS] rate 85% vs 73%) with a favorable benefit-risk profile for previously treated MSI-H/dMMR mCRC (Overman et al. JCO 2018). NIVO+low-dose IPI also demonstrated robust and durable clinical benefit in first-line MSI-H/dMMR mCRC (INV ORR 64%; 12-mo INV PFS rate 77%; 12-mo OS rate 84%; Lenz et al. ASCO 2019, #3521). To date, no prospective phase 3 studies have reported results for anti–PD-1, anti–PD-1 + anti–CTLA-4, or CT in MSI-H/dMMR mCRC; these treatments will be evaluated in the international, multicenter, open-label, randomized, phase 3 CheckMate 8HW (NCT04008030) study. Methods: Approximately 494 pts aged ≥18 years with histologically confirmed recurrent or mCRC, irrespective of prior treatment with CT and/or targeted agents, not amenable to surgery, and with known tumor MSI-H or dMMR status, and Eastern Cooperative Oncology Group performance status ≤1 will be randomized to receive NIVO, NIVO+IPI, or investigator’s choice CT (pts in the CT arm can receive NIVO+IPI upon progression). The primary endpoint is PFS, assessed by blinded independent central review (BICR). Secondary endpoints include PFS by INV, ORR and disease control rate by BICR and INV, OS, time to and duration of response. Exploratory endpoints include safety. Clinical trial information: NCT04008030.

scholarly journals Repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy (ePIPAC) with oxaliplatin as a palliative monotherapy for isolated unresectable colorectal peritoneal metastases: protocol of a Dutch, multicentre, open-label, single-arm, phase II study (CRC-PIPAC)

BMJ Open ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. e030408 ◽  
Author(s):  
Koen P Rovers ◽  
Robin J Lurvink ◽  
Emma CE Wassenaar ◽  
Thomas JM Kootstra ◽  
Harm J Scholten ◽  
...  
Keyword(s):  
Phase Ii ◽  
Palliative Treatment ◽  
Phase Ii Study ◽  
Performance Status ◽  
Tumour Response ◽  
Competent Authority ◽  
Peritoneal Metastases ◽  
Open Label ◽  
Link Type ◽  
Number Of Patients

IntroductionRepetitive electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX) is offered as a palliative treatment option for patients with isolated unresectable colorectal peritoneal metastases (PM) in several centres worldwide. However, little is known about its feasibility, safety, tolerability, efficacy, costs and pharmacokinetics in this setting. This study aims to explore these parameters in patients with isolated unresectable colorectal PM who receive repetitive ePIPAC-OX as a palliative monotherapy.Methods and analysisThis multicentre, open-label, single-arm, phase II study is performed in two Dutch tertiary referral hospitals for the surgical treatment of colorectal PM. Eligible patients are adults who have histologically or cytologically proven isolated unresectable PM of a colorectal or appendiceal carcinoma, a good performance status, adequate organ functions and no symptoms of gastrointestinal obstruction. Instead of standard palliative treatment, enrolled patients receive laparoscopy-controlled ePIPAC-OX (92 mg/m2body surface area (BSA)) with intravenous leucovorin (20 mg/m2BSA) and bolus 5-fluorouracil (400 mg/m2BSA) every 6 weeks. Four weeks after each procedure, patients undergo clinical, radiological and biochemical evaluation. ePIPAC-OX is repeated until disease progression, after which standard palliative treatment is (re)considered. The primary outcome is the number of patients with major toxicity (grade ≥3 according to the Common Terminology Criteria for Adverse Events v4.0) up to 4 weeks after the last ePIPAC-OX. Secondary outcomes are the environmental safety of ePIPAC-OX, procedure-related characteristics, minor toxicity, postoperative complications, hospital stay, readmissions, quality of life, costs, pharmacokinetics of oxaliplatin, progression-free survival, overall survival, and the radiological, histopathological, cytological, biochemical and macroscopic tumour response.Ethics and disseminationThis study is approved by an ethics committee, the Dutch competent authority and the institutional review boards of both study centres. Results are intended for publication in peer-reviewed medical journals and for presentation to patients, healthcare professionals and other stakeholders.Trial registration numberNCT03246321, Pre-results;ISRCTN89947480, Pre-results; NTR6603, Pre-results; EudraCT: 2017-000927-29, Pre-results.

scholarly journals Postoperative XELOX therapy for patients with curatively resected high-risk stage II and stage III rectal cancer without preoperative chemoradiation: a prospective, multicenter, open-label, single-arm phase II study

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Tsunekazu Mizushima ◽  
Masataka Ikeda ◽  
Takeshi Kato ◽  
Atsuyo Ikeda ◽  
Junichi Nishimura ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
High Risk ◽  
Local Recurrence ◽  
Phase Ii ◽  
Group Performance ◽  
Phase Ii Study ◽  
Preoperative Chemoradiation ◽  
Stage Ii ◽  
Stage Iii ◽  
Open Label

Abstract Background Preoperative 5-FU-based chemoradiation is currently a standard treatment for advanced rectal cancer, particularly in Western countries. Although it reduced the local recurrence, it could not necessarily improve overall survival. Furthermore, it can also produce adverse effects and long-term sphincter function deficiency. Adjuvant oxaliplatin plus capecitabine (XELOX) is a recommended regimen for patients with curatively resected colon cancer. However, the efficacy of postoperative adjuvant therapy for rectal cancer patients who have not undergone preoperative chemoradiation remains unknown. We aimed to evaluate the efficacy of surgery and postoperative XELOX without preoperative chemoradiation for treating rectal cancer. Methods We performed a prospective, multicenter, open-label, single arm phase II study. Patients with curatively resected high-risk stage II and stage III rectal cancer who had not undergone preoperative therapy were treated with a 120 min intravenous infusion of oxaliplatin (130 mg/m2) on day 1 and capecitabine (2000 mg/m2/day) in 2 divided doses for 14 days of a 3-week cycle, for a total of 8 cycles (24 weeks). The primary endpoint was 3-year disease-free survival (DFS). Results Between August 2012 and June 2015, 60 men and 47 women with a median age was 63 years (range: 29–77 years) were enrolled. Ninety-three patients had Eastern Cooperative Oncology Group performance status scores of ‘0’ and 14 had scores of ‘1’. Tumors were located in the upper and lower rectums in 54 and 48 patients, respectively; 8 patients had stage II disease and 99 had stage III. The 3-year DFS was 70.1% (95% confidence interval, 60.8–78.0%) and 33 patients (31%) experienced recurrence, most commonly in the lung (16 patients) followed by local recurrence (9) and hepatic recurrence (7). Conclusions Postoperative XELOX without preoperative chemoradiation is effective for rectal cancer and provides adequate 3-year DFS prospects. Trial registration This clinical trial was registered in the University Hospital Medical Information Network registry system as UMIN000008634 at Aug 06, 2012.

scholarly journals Axitinib plus avelumab in the treatment of recurrent glioblastoma: a stratified, open-label, single-center phase 2 clinical trial (GliAvAx)

2020 ◽  
Vol 8 (2) ◽  
pp. e001146
Author(s):  
Gil Awada ◽  
Laila Ben Salama ◽  
Jennifer De Cremer ◽  
Julia Katharina Schwarze ◽  
Lydia Fischbuch ◽  
...  
Keyword(s):  
Adverse Events ◽  
Group Performance ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Synergistic Activity ◽  
Open Label ◽  
Corticosteroid Dose

BackgroundNo treatment demonstrated to improve survival in patients with recurrent glioblastoma (rGB) in a randomized trial. Combining axitinib with the programmed cell death ligand 1 blocking monoclonal antibody avelumab may result in synergistic activity against rGB.MethodsAdult patients with rGB following prior surgery, radiation therapy and temozolomide chemotherapy were stratified according to their baseline use of corticosteroids. Patients with a daily dose of ≤8 mg of methylprednisolone (or equivalent) initiated treatment with axitinib (5 mg oral two times per day) plus avelumab (10 mg/kg intravenous every 2 weeks) (Cohort-1). Patients with a higher baseline corticosteroid dose initiated axitinib monotherapy; avelumab was added after 6 weeks of therapy if the corticosteroid dose could be tapered to ≤8 mg of methylprednisolone (Cohort-2). Progression-free survival at 6 months (6-m-PFS%), per immunotherapy response assessment for neuro-oncology criteria, served as the primary endpoint.ResultsBetween June 2017 and August 2018, 54 patients (27 per cohort) were enrolled and initiated study treatment (median age: 55 years; 63% male; 91% Eastern Cooperative Oncology Group Performance Status 0–1). Seventeen (63%) patients treated in Cohort-2 received at least one dose of avelumab. The 6-m-PFS% was 22.2% (95% CI 6.5% to 37.9%) and 18.5% (95% CI 3.8% to 33.2%) in Cohort-1 and Cohort-2, respectively; median overall survival was 26.6 weeks (95% CI 20.8 to 32.4) in Cohort-1 and 18.0 weeks (95% CI 12.5 to 23.5) in Cohort-2. The best objective response rate was 33.3% and 22.2% in Cohort-1 and Cohort-2, respectively, with a median duration of response of 17.9 and 19.0 weeks. The most frequent treatment-related adverse events were dysphonia (67%), lymphopenia (50%), arterial hypertension and diarrhea (both 48%). There were no grade 5 adverse events.ConclusionThe combination of avelumab plus axitinib has an acceptable toxicity profile but did not meet the prespecified threshold for activity justifying further investigation of this treatment in an unselected population of patients with rGB.

scholarly journals Randomized Open-Label Phase II Study of Decitabine in Patients With Low- or Intermediate-Risk Myelodysplastic Syndromes

2013 ◽  
Vol 31 (20) ◽  
pp. 2548-2553 ◽  
Author(s):  
Guillermo Garcia-Manero ◽  
Elias Jabbour ◽  
Gautam Borthakur ◽  
Stefan Faderl ◽  
Zeev Estrov ◽  
...  
Keyword(s):  
Phase Ii ◽  
Low Dose ◽  
De Novo ◽  
Phase Ii Study ◽  
Cytogenetic Response ◽  
Open Label ◽  
End Points ◽  
Improvement Rate ◽  
Transfusion Independence ◽  
Open Label Phase

Purpose This open-label, randomized phase II trial assessed efficacy and tolerability of two low-dose regimens of subcutaneous (SC) decitabine in patients with low- or intermediate-1–risk myelodysplastic syndrome (MDS). Patients and Methods Patients received decitabine 20 mg/m2 SC per day for 3 consecutive days on days 1, 2, and 3 every 28 days (schedule A) or 20 mg/m2 SC per day once every 7 days on days 1, 8, and 15 every 28 days (schedule B) for up to 1 year. Primary efficacy end point was overall improvement rate (OIR: complete remission [CR], partial remission [PR], marrow CR [mCR], or hematologic improvement [HI]). Secondary end points were HI, transfusion independence, cytogenetic response, overall survival (OS), and time to acute myeloid leukemia or death. Results Efficacy and safety populations were identical: schedule A, n = 43; schedule B, n = 22. Median time from MDS diagnosis to treatment was 3.6 months; 89% had de novo MDS. The trial was terminated early on achievement of protocol-defined OIR superiority of schedule A over schedule B; OIR was 23% for schedule A (seven CRs, three HIs) and 23% for schedule B (one mCR, one PR, three HIs). No differences were observed in secondary end points. Median OS was not reached; approximately 70% of patients were alive at 500 days. Patients in schedule A (67%) and schedule B (59%) were RBC/platelet independent on study. The most frequent drug-related adverse events overall were neutropenia (28% v 36%), anemia (23% v 18%), and thrombocytopenia (16% v 32%). Conclusion In this phase II study, low-dose decitabine showed promising results in patients with low- or intermediate-1–risk MDS.

A Multicentre Phase II Study of the Aminopeptidase Inhibitor, CHR- 2797, in the Treatment of Elderly and/or Previously Treated patients with Acute Myeloid Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 961-961 ◽  
Author(s):  
B. Lowenberg ◽  
F. Davies ◽  
C. Müller-Tidow ◽  
Ulrich Dührsen ◽  
A. Burnett ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Clinical Activity ◽  
Open Label ◽  
Elderly Aml ◽  
Previously Treated Patients ◽  
Previously Treated

Abstract Tosedostat (TSD, CHR-2797) is an aminopeptidase inhibitor that selectively depletes amino acid pools in malignant cells, resulting in anti-proliferative, pro-apoptotic and antiangiogenic effects. In a phase I study, treatment with TSD resulted in complete remission in a number of refractory AML patients. The primary objective of this phase II study was to determine whether TSD was a sufficiently effective therapy to warrant pivotal studies. Methods. This was an open label, single agent, phase II study to assess clinical activity of TSD in elderly and/or previously treated patients with AML/MDS. Patients were treated with once daily oral doses of the maximum acceptable dose (130 mg) of TSD for up to 84 days. Further treatment was allowed if, in the opinion of the investigator, this was considered to be beneficial. Clinical responses were assessed by monthly bone marrow aspirates and weekly hematological assessments. Results. Of the 41 TSD-treated patients with AML (n=38) or MDS (n=3), who were enrolled between March and October 2007, 27 were male, 14 female, with a mean age of 67 years (range 34–82). The median performance status (ECOG) at baseline was 1 (range 0–2). Twelve (31.6%) AML patients and 2 (66.7%) MDS patients were chemotherapy naïve, and 9 (23.7%) AML patients had either secondary disease or adverse cytogenetics. For 16 (39%) patients, treatment with TSD was a second or later salvage attempt. Thirty two patients (30 AML, 2 MDS-RAEB1 and 2) received ≥28 days treatment, and 21 (51.2%) patients completed the formal 84-day study period (19 AML, 2 MDS). Nine (22%) of the patients (7 AML, 2 MDS) continued treatment with TSD after 84 days, and 6 (15%) patients were on TSD in total for more than 6 months (4 AML, 2 MDS). Ten (26.3%) of the AML patients responded to treatment; amongst these, 2 patients received TSD as 2nd/3rd salvage therapy, and a further 2 patients did not show a complete response (CR) after 2 previous induction courses of chemotherapy. Three AML patients achieved a CR (< 5% blasts in bone marrow), of whom 2 were in durable remission (232 days, continuing*; 171 days), and 7 had a partial response (PR, 5–15% blasts) lasting approximately 1–3 months. Two (66.7%) of the MDS patients also responded to treatment with TSD; these patients maintained stable disease for more than 6 months. All responders (CR, PR and SD) were >60 years at the time of the first dose. Median overall survival in AML patients was 130 days (range 8 – 478 days*). The most frequently reported adverse events were: fatigue (61%), thrombocytopenia (49%), pyrexia (39%), peripheral edema (39%) and diarrhea (34%); 9 (22%) patients withdrew due to drug related toxicity. TSD had no effect on hemoglobin or neutrophils. Conclusions. This study in patients with advanced AML/MDS with adverse prognosis demonstrates the anti-leukemic activity of TSD in elderly AML patients, as measured by CR and decreases in leukemic blasts. In addition, 2 relapsed high risk MDS patients achieved disease stabilization. TSD at 130mg qd is also very well tolerated over a long period of exposure (6–10 months). These results support further pivotal studies with TSD in elderly AML and MDS patients.

A phase II study of ixabepilone (BMS 247550) in metastatic renal cell carcinoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14646-14646 ◽  
Author(s):  
E. M. Posadas ◽  
S. Undevia ◽  
A. D. Colevas ◽  
E. Manchen ◽  
E. E. Vokes ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Clear Cell ◽  
Phase Ii Study ◽  
Performance Status ◽  
Response To Therapy ◽  
Synthetic Analog ◽  
Minor Response

14646 Introduction Ixabepilone (BMS) is a semi-synthetic analog of Epothilone B that functions as a microtubule stabilizer and has anti-cancer effects in several cancers including renal cell carcinoma (RCC) (Zhuang, ASCO 2004). The initial phase II study in RCC utilized a difficult and unconventional dosing schedule (6 mg/m2 IV days 1–5 every 21 days). Hence, this phase II study in RCC was designed to verify previous observations and to test the safety, feasibility, and activity of administering BMS once every 3 weeks- a schedule used in other malignancies. Methods Treatment consists of BMS 40 mg/m2 IV on day 1 every 3 weeks. Eligibility included metastatic RCC with clear or non-clear cell histology, no limits on the number of previous treatments, performance status 0–2, and normal organ function. The primary endpoint is the overall response rate by RECIST criteria on radiologic evaluation conducted every 9 weeks. Accrual to the full planned 41 patients (pts) will proceed provided that 2 or more responses are observed in the first 21 pts. Results Ten pts have enrolled (4 clear cell) with 1 declining participation prior to receiving any treatment. Eight pts have completed at least 3 cycles. Grade 3–4 toxicities include lymphopenia-2, diarrhea-2, alopecia-1, and infection-1. Grade 1–2 toxicities seen in more than 50% of pts include alopecia, neuropathy, nausea, fatigue, anemia, and lymphopenia. We have observed 1 unconfirmed partial response of short duration and 1 pt exhibited stable disease with a minor response but discontinued treatment due to excessive neurotoxicity. Three pts continue on treatment. Conclusions Toxicity at 40 mg/m2 IV on day 1 every 3 weeks is higher than previously reported with the daily x 5 schedule. While lymphopenia, diarrhea, neuropathy, and fatigue are all expected adverse events, the rates of toxicity across all grades is higher than previous reports. VHL mutation analysis is planned and will be correlated with response to therapy. Accrual and pt follow up continue. No significant financial relationships to disclose.

MAVERICC: A randomized phase II study of mFOLFOX6-bevacizumab (BV) versus FOLFIRI-BV with prospective biomarker stratification in previously untreated metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS3635-TPS3635 ◽  
Author(s):  
Sachdev P. Thomas ◽  
Suprith Badarinath ◽  
Richard H. Greenberg ◽  
Sang Y. Huh ◽  
Kulumani M Sivarajan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Hepatic Metastases ◽  
Predictive Biomarkers ◽  
Snp Markers ◽  
Open Label ◽  
Ecog Performance Status ◽  
The Impact

TPS3635^ Background: The identification of prognostic and predictive biomarkers could significantly improve the risk-benefit ratio and cost-effectiveness of 1st-line mCRC regimens. This is the first prospective study of tumoral ERCC1 (chemo-resistance marker to platinum compounds) and plasma VEGF-A as potential biomarkers for oxaliplatin- and BV-containing regimens, respectively, in an effort to further define the optimal chemotherapy backbone with biologic therapies, including BV, for mCRC. Methods: In this randomized, open-label, global, phase II study, patients (N=360) with histologically or cytologically confirmed CRC and ≥1 measurable metastatic lesion are stratified at screening by tumoral ERCC1 mRNA expression (high vs low, cutoff of 1.7 [ERCC1/β-actin mRNA]). Eligibility criteria include completion of adjuvant therapy >12 months before screening and an ECOG performance status ≤1. Blood samples are collected to quantify plasma VEGF-A levels. Patients within each ERCC1 stratification group are randomized 1:1 to mFOLFOX6-BV or FOLFIRI-BV administered in 2-week cycles. BV will be given at a dose of 5 mg/kg IV q2w. Patients will remain on study treatment until disease progression (PD) or unacceptable toxicity. If oxaliplatin or irinotecan need to be discontinued, BV and 5-fluorouracil or capecitabine are to be continued until PD. The primary objectives are: 1) to assess ERCC1 and VEGF-A as biomarkers of progression-free survival (PFS) for oxaliplatin- and BV-containing regimens in 1st-line mCRC, and 2) within ERCC1 high patients, to test whether FOLFIRI-BV is associated with a prolonged 1st-line PFS compared to mFOLFOX6-BV. Secondary objectives include assessing the impact of these markers on overall survival, objective response, hepatic metastases resection, and safety. Exploratory endpoints include correlative analyses with additional tumor tissue, blood, and SNP markers. The first patient was enrolled in August 2011. An interim biomarker distribution assessment of the first 100 patients is planned, and the evaluation of the primary endpoints is estimated for early 2015. Clinicaltrials.gov: NCT01374425.

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