Early data from a phase II trial investigating the combination of pembrolizumab (PEM) and entinostat (ENT) in relapsed and refractory (R/R) Hodgkin lymphoma (HL).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20018-e20018 ◽  
Author(s):  
David J. Sermer ◽  
Santosha Adipudi Vardhana ◽  
Ashley Ames ◽  
Erin Biggar ◽  
Alison J. Moskowitz ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Statistical Significance ◽  
Single Agent ◽  
Hdac Inhibitors ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Immune Recognition ◽  
Cytokine Analysis ◽  
Early Results

e20018 Background: Histone deacetylase (HDAC) inhibitors have single agent activity in various types of lymphoma. They have been shown to restore antigen-specific immune recognition in cancer cells and to downregulate PD-1 expression in circulating T lymphocytes. In preclinical studies, the combination of HDAC inhibitors and anti-PD-1 antibodies acts synergistically against various tumor models in mice. Accordingly, we investigated the safety and efficacy of the novel combination of the HDAC inhibitor ENT and the PD-1-blocking antibody PEM in patients with R/R HL. Methods: Patients with R/R HL received ENT 5-7 mg orally once weekly and PEM 200 mg intravenously once every three weeks. The primary objective is overall response rate (ORR) and 12-month progression-free survival (PFS). Multiplexed serum cytokine analysis of 20 pro-inflammatory cytokines and chemokines was performed on sera from peripheral blood samples collected at baseline and at 21 days on treatment. Results: At data cutoff on 2/5/20, 14 patients with HL have been enrolled. Out of 13 evaluable patients, 12 responded (92% ORR), including 3 who progressed on prior anti-PD-1 therapy. With a median duration of follow-up of 176 days (21-632), 9 patients are currently receiving treatment on study, 2 discontinued due to toxicity, 1 for progression, and 2 for consolidation with transplant or radiation. After 21 days on treatment, there was a decrease in median serum levels of eotaxin (-39%, p = 0.002), eotaxin-3 (-56%, p = 0.04), MDC (-78%, p = 0.025), MIP1a (-60%, p = 0.025), and TARC (-98%, p < 0.001) and a 3-fold increase in median levels of IFNγ (p = 0.032). There was an association between extent of tumor reduction and greater decrease in the cytokines eotaxin-3 (-62%, p = 0.064), MDC (-90%, p = 0.064), and MIP1a (-85%, p = 0.064), which trended towards statistical significance. Out of 22 total patients enrolled in this study (including 8 patients with follicular lymphoma), 62% had grade ≥3 adverse events (AE), which were predominantly hematologic, including neutropenia (48%), thrombocytopenia (19%), and anemia (10%). Immune-related AEs included 3 cases of hypothyroidism, 2 cases of hepatitis and 1 case of pneumonitis. Four patients who experienced serious AEs due to pericarditis (n = 2), hemophagocytic lymphohistiocytosis, and bullous dermatitis were taken off study. Conclusions: Early results from this ongoing phase II clinical trial suggest that the combination of PEM and ENT is safe with encouraging responses in HL. Clinical trial information: NCT03179930 .

scholarly journals CTIM-15. PRELIMINARY RESULTS OF A PHASE II STUDY OF NIVOLUMAB WITH HYPOFRACTIONATED RE-RADIATION AND BEVACIZUMAB FOR RECURRENT MGMT METHYLATED GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii36-ii36
Author(s):  
Christian Grommes ◽  
Minesh Mehta ◽  
Alexandra Miller ◽  
Mariza Daras ◽  
Anna Piotrowski ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Disease Recurrence ◽  
Primary Objective ◽  
Significant Finding ◽  
Trial Treatment

Abstract Standard of standard of care for glioblastoma (GBM) remains unsatisfactory with universal disease recurrence and a median survival of &lt; 2 years. Immune checkpoint inhibitors (ICI) have shown limited single-agent activity in GBM thus far. GBMs with methylated MGMT promoter and no baseline corticosteroid dependence may be most likely to derive benefit from ICI. The combination of ICIs with radiation has shown promising activity in other human cancers. Combining nivolumab and re-RT/bevacizumab in GBM may augment ICI activity through immunogenic effects of radiation, may reduce the risk of radiation necrosis by addition of bevacizumab at the time of radiation, and may reduce the need for corticosteroids. In this multicenter phase II study, nivolumab is combined with re-irradiation and optional concurrent bevacizumab followed by nivolumab in patients with first recurrence of IDH-wildtype and MGMT methylated glioblastoma. Primary objective is to improve 1-year overall survival (OS) from 33 (based on EORTC 26101) to 50%. Nine-three patients are required to show a significant finding with an α of 0.05 and 81% power. Thirteen of 93 patient (14%) have been enrolled with a median age of 59 (range 42–71) with a median KPS of 90 (range 70–90). Treatment has been tolerated well without any grade ≥ 4 toxicities and only one grade 3 (amylase elevation). The most common adverse events were pruritus and hypothyroidism in 3/13 (23%). The median progression-free survival (PFS) is 7 months with a 6months PFS of 55.6%. The 12months OS is 66.7%. Patients with recurrent MGMT methylated, IDH-wildtype glioblastoma tolerate trial treatment with acceptable toxicities. Clinical efficacy in the first patients enrolled shows a promising effect. Enrollment is ongoing.

Encouraging activity of bicalutamide and everolimus in castration-resistant prostate cancer (CRPC): Early results from a phase II clinical trial.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 157-157
Author(s):  
C. Pan ◽  
P. Ghosh ◽  
P. Lara ◽  
D. Robles ◽  
L. Beckett ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Disease Progression ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Tumor Formation ◽  
Mtor Pathway ◽  
Phase Ii Clinical Trial ◽  
Castration Resistant Prostate Cancer ◽  
Early Results ◽  
Psa Response

157 Background: Multiple signaling pathways are involved in the development of CRPC. We previously showed that the mTOR pathway is activated in CRPC cell lines while inhibition of this pathway results in upregulation of androgen receptor (AR) signaling (Wang et al, Oncogene. 2008). Simultaneous blockade of the mTOR and AR pathways synergize in inducing PCa cell death and delaying tumor formation in mouse models. We hypothesize that simultaneous blockade of the AR and mTOR pathways in CRPC patients with bicalutamide and everolimus will result in improved efficacy compared to bicalutamide alone. Methods: A phase II clinical trial with a lead-in safety phase was designed to determine the efficacy and tolerability of the bicalutamide and everolimus combination in CRPC patients compared with bicalutamide alone. Patients must have histologically confirmed disease and demonstrated disease progression (either by PSA or radiographically) while on androgen deprivation therapy. At the lead-in phase, all patients receive both agents. At the phase II stage, patients are randomized to bicalutamide +/− everolimus. The primary endpoint is PSA response. The second endpoints include progression-free survival, time-to-treatment failure, overall survival and toxicity. Here, we report the results of the lead-in phase. Results: Eight patients were recruited at the lead-in phase. The bicalutamide/everolimus combination was well tolerated with no unexpected toxicities. Six of 8 patients have had PSA response after at least 8 weeks of therapy and the remaining two patients had stable PSA response. The median time to disease progression was 6.8 months. Nine patients have been recruited at the phase II stage so far. This clinical trial is being subcontracting to the other sites of the California Cancer Consortium. Tumor and blood specimens are being collected for molecular correlative studies of mTOR pathway markers. Conclusions: The rational combination of bicalutamide and everolimus appears to have promising anti-tumor activity and an acceptable toxicity profile. The randomized phase of the clinical trial is currently ongoing and will be reported. Supported by Novartis. [Table: see text]

Phase II trial of anti-transforming growth factor-beta (TGFß) monoclonal antibody GC1008 in relapsed malignant pleural mesothelioma (MPM).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7077-7077 ◽  
Author(s):  
James Stevenson ◽  
Hedy Lee Kindler ◽  
Daniel Schwed ◽  
Anjana Ranganathan ◽  
Mona Jacobs-Small ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Phase Ii Trial ◽  
Treatment Plan ◽  
Single Agent ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Modified Recist

7077 Background: TGFβ is a pleiotropic cytokine overexpressed by MPM. Based on preclinical data documenting a key role for TGFβ in promoting growth and progression of MPM, we are conducting a phase II trial of GC1008 in patients (pts) with progressive MPM. Methods: Pts with progressive MPM by modified RECIST criteria and PS 0-1 with 1-2 prior systemic therapies (at least 1 pemetrexed-based) are eligible. Treatment plan: GC1008 3mg/kg IV over 90 minutes every 21 days. Responses are assessed by modified RECIST every 6 weeks. The primary endpoint is progression-free survival (PFS) rate at 3 months; secondary objectives include safety with GC1008, response rate by modified RECIST, time to progression (TTP), and overall survival (OS). Results: The modified Gehan stage 1 stopping criterion of 1/13 pts with 3 month PFS has been exceeded. To date, 13 pts (10 PS 0; 3 PS 1) with MPM (median age 69; 2F, 11M; 11 epithelial, 1 sarcomatoid, 1 biphasic) enrolled. Treatment-related toxicities include G1/2 fatigue (3 pts), nausea (1 pt) and xerosis (1 pt). Other adverse events possibly related to GC1008 were rapid disease progression in 1 pt after 2 cycles, and G2 skin keratoacanthoma in 1 pt after 5 cycles. Three pts met the primary objective of 3 month PFS at 4.1, 4.2 and 9 months each. Stable disease (SD) was seen in 3 pts (23%). Median TTP is 1.4 months (95% CI 1.2-∞); median OS is 13 months (95% CI 6-∞). Increased serum mesothelin levels have closely tracked disease progression. Serum from 6/13 pts showed new antibodies against MPM tumor lysates as measured by immunoblotting. Two of 3 pts with SD had anti-tumor antibody responses. Mean baseline plasma level of TGFβ was 2447 pg/ml but did not correlate with baseline plasma TGFβ or TTP. Conclusions: GC1008 was well tolerated in pretreated MPM patients. SD occurred in 3 pts, all with prior disease progression. Evidence for humoral anti-tumor immunity was seen in nearly half of enrollees and in 2 of 3 pts with SD. OS compares favorably to prior single-agent studies in pretreated MPM.

IMAGE, a randomized phase Ib/II study of elisidepsin (E) as a single agent in pretreated advanced gastroesophageal (GE) cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 92-92 ◽  
Author(s):  
Ramon Salazar ◽  
Jean Philippe Metges ◽  
David Alan Anthoney ◽  
Gianluca Laus ◽  
Maria Alsina Maqueda ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Phase Ii ◽  
Single Agent ◽  
Progression Free Survival ◽  
Optimal Dose ◽  
Primary Objective ◽  
Phase Ib ◽  
Flat Dose

92 Background: E is a new marine compound with broad in vitro/in vivo antitumor activity. Low μM concentrations lead to cell-death through membrane permeabilization. E has shown evidence of activity in pre-treated GE patients (pts) in phase I trials. Methods: The primary objective was to determine the tolerability and efficacy of E in pts with GE cancer after 1-2 prior chemotherapy (CT) lines. Initially, dose was optimized (Phase Ib) in two different schedules: a fixed flat dose (FD) of intravenous (i.v) E (8 and 10 mg), in 24h, biweekly (Arm A) and i.v E (3.0 and 3.75mg), in 3h, weekly (Arm B). After dose optimization patients were included and stratified by histology to each optimal dose (Phase II) to determine the rate of progression-free survival at week 16 ± 1 (PFS4) in an intention to treat analysis. If at least two out of 15 pts reached PFS4, recruitment would continue to a maximum of 40 pts per arm. Results: A total of 45 pts were recruited, 12 pts into Phase Ib (Arm A/B: 6/6 pts) and 33 pts into Phase II (Arm A/B: 15/18 pts). Median age was 60 years (35–81 years), 39 were males and ECOG PS was 1 in 75% of pts. Tumour sites were gastric (32% pts), esophageal (39% pts) and esophago-gastric junction (30% pts). Ninety percent of pts had metastatic disease, 31.8% of which had liver metastasis; 55% of pts had two prior lines of CT . No DLTs occurred during the first cycle in the Phase Ib. The optimal dose for Arm A was 10 mg FD, 24h, biweekly; the optimal dose for Arm B was 3.75mg FD, 3h, weekly. Two patients reached PFS4 in Phase Ib (Arm A). Only one patient reached PFS4 in Phase II (Arm A). No objective responses were observed. Therefore, protocol criteria for further recruitment were not met. The safety profile showed grade 1-2 toxicity pruritus (29.5%), nausea (15.9%), vomiting (6.8%) and fatigue (25%). Grade 3-4 toxicity consisted of asymptomatic reversible liver enzyme increases in 20.5% of patients. Conclusions: E is a very tolerable drug with a unique mechanism of action. In the current setting of non-stratified advanced GE patients, E has insufficient antitumor activity to warrant further investigation. Clinical trial information: 2010-020325-40.

Phase II study of PS-341 (bortezomib) with or without irinotecan in patients (pts) with advanced gastric adenocarcinomas (AGA)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14040-14040 ◽  
Author(s):  
A. J. Ocean ◽  
F. Schnoll-Sussman ◽  
R. Keresztes ◽  
X. Chen ◽  
S. Holloway ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Response Rate ◽  
Single Agent ◽  
Xenograft Model ◽  
Progression Free Survival ◽  
Median Number ◽  
Primary Objective ◽  
Free Survival ◽  
Radiologic Evaluation

14040 Background: We are conducting a phase II trial of the proteasome inhibitor, PS-341, with or without irinotecan in pts with AGA. The combination of PS-341 and irinotecan has been studied in preclinical tumor models including a murine xenograft model of colon cancer, where the combination achieved significantly more tumor shrinkage than either agent alone. The primary objective of this study is to determine response rates, toxicities, progression-free survival, and overall survival in pts with AGA receiving PS-341 alone or in combination with irinotecan. Methods: All pts had gastric adenocarcinoma beyond the scope of surgical resection, measurable disease, and normal bone marrow, hepatic and renal function. All gave informed consent. In previously untreated patients, PS-341 was administered at 1.3 mg/m2 on days 1, 4, 8, and 11 as IV bolus every 21 days. Irinotecan was administered IV at 125 mg/m2 over 90 mins on days 1 and 8 every 21 days (Arm A). For previously treated patients, PS-341 was administered as a single agent at 1.3mg/m2 on days 1, 4, 8, 11 as an IV bolus every 21 days (Arm B). Radiologic evaluation and tumor measurements were performed every 8 weeks. Results: Thirty-seven pts have been enrolled; 29 are evaluable (4 never treated, 4 TETE). Twenty-two pts were treated in Arm A, and 11 in Arm B. All pts were eligible and the 29 treated pts were fully evaluable. Median age 58 (33–87); 26 males/7 females; median number of cycles received was 2.0. Most common toxicities: Grade 4 cardiac arrest (1), stomach perforation (1), leukopenia (2), diarrhea (1), edema (1); Grade 3 nausea (6), vomiting (7), diarrhea (4), febrile neutropenia (3), thrombocytopenia (6), anemia (6); Grade 5 death (3). Severe toxicities likely attributed to disease progression. Response rate was 33% for Arm A, 9% for Arm B. Progression-free survival was 1.8 mo. in Arm A, 1.4 mo. in Arm B. Median overall survival was 4.8 mo. in Arm A, 5.4 mo. in Arm B. Conclusions: The combination of PS-341 and irinotecan, a non-cisplatin containing therapy, is active in AGA and should be considered a key regimen. Monotherapy with PS-341 has a 9% response rate in this population of pre-treated patients with advanced disease. Accrual to this study is continuing. [Table: see text]

Avelumab and cetuximab in combination with FOLFOX in patients with previously untreated metastatic colorectal cancer (MCRC): The phase II AVETUX-CRC trial (AIO KRK 0216).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS3620-TPS3620 ◽  
Author(s):  
Alexander Stein ◽  
Mascha Binder ◽  
Carsten Bokemeyer ◽  
Salah Eddin Al Batran ◽  
Axel Hinke ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Mismatch Repair ◽  
Phase Ii ◽  
Type I Error ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Type I ◽  
Translational Research Program ◽  
Clinical Trial Information

TPS3620 Background: Inhibition of the PD-1/L1 axis has shown to improve survival as single agent in a variety of tumor types. The efficacy of single agent PD-1/L1 inhibition in patients with treatment refractory MCRC seems to be limited to hypermutated tumors characterized by mismatch repair deficiency. 1st line chemotherapy (e.g. FOLFOX) with cetuximab for patients with RAS/BRAF wildtype MCRC result in objective response rates of about 60%, thus substantial antigen release will likely occur triggering immune control. Furthermore, the induction of immunogenic cell death has been recently shown for cetuximab-based regimen. Thus, the evaluation of FOLFOX and cetuximab in combination with avelumab in 1st line MCRC is of particular interest. Methods: AVETUX is a single arm exploratory phase II investigator initiated trial. Patients with RAS/BRAF wildtype MCRC will be included independent of mismatch repair status to receive mFOLFOX6 and cetuximab in combination with avelumab (10mg/kg from day 1 of cycle 2 onwards). Treatment with avelumab is limited to a maximum of 18 months. Primary endpoint is 12month progression-free survival rate, which should be increased from 40% to 57%, with type I error of 10% and 80% power, leading to a sample size of 43 patients. An early stopping rule will be applied in case of an increase in toxicity after the first 15 patients received at least two months of treatment. The trial is flanked by a large translational program including immunoprofiling to determine and correlate the respective immune response signatures with clonal dynamics (RAS/EGFR). Recruitment will start in 11 German sites early 2017. Clinical trial information: EudraCT No 2016-004434-26. Conclusion: The AVETUX trial will determine the feasibility and early efficacy of FOLFOX and cetuximab combined with avelumab in 1st line MCRC. The translational research program will shed light on the potential mode of action of this novel combination. Clinical trial information: 2016-004434-26.

Evolve: A post PARP inhibitor clinical translational phase II trial of cediranib-olaparib in ovarian cancer—A Princess Margaret Consortium – GCIG Phase II Trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5521-5521 ◽  
Author(s):  
Stephanie Lheureux ◽  
Ana Oaknin ◽  
Swati Garg ◽  
Jeffrey Bruce ◽  
Neesha C. Dhani ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Tumor Biopsy ◽  
Ps Ii

5521 Background: PARP inhibitors (PARPi) are approved therapies in high grade serous ovarian cancer (HGSOC). There are few studies after PARPi progression and correlation with dynamic changes in resistance. We hypothesized that PARPi resistance could be overcome by adding an anti-angiogenic. Methods: We report the first phase 2 trial assessing the combination of olaparib and cediranib after PARPi failure in HGSOC. This investigator initiated study included three cohorts of 10 evaluable patients (pts): i) platinum sensitive post PARPi (PS), ii) platinum resistant post PARPi (PR) and iii) exploratory cohort of pts re-challenged with chemotherapy post PARPi progression (PE) (NCT02681237). The primary objective was to determine objective response rate by RECIST v1.1 and progression free survival (PFS) at 16 weeks. Secondary objectives were to evaluate safety, PFS, overall survival (OS) and mechanisms of PARPi resistance. Pts who had radiographic progression on any PARPi were eligible. Archival tumor at initial diagnosis and baseline tumor biopsy at PARPi progression were mandatory. Pts received olaparib tablets 150mg BID with cediranib 20mg QD until progression or unacceptable toxicity. CT scans were performed every 8 weeks. Whole exome and RNA sequencing were performed on paired tumors tissues. Results: Thirty-four pts were enrolled. BRCA1/2 mutations were found in 9/11 PS, 8/10 PR and 7/13 PE pts. By RECIST1.1, four partial responses were observed (2 in PR and 2 in PE cohorts) and 18 stable disease. The 16−week PFS was 54.5% (31.8−93.6) in PS, 50% (26.9−92.9) in PR and 36% (15.6−82.8) in PE, respectively. OS at 1 year was 81.8% (61.9−100) in PS, 64.8% (39.3−100) in PR and 39.1% (14.7−100) in PE. Main related adverse events were anemia, hypertension, diarrhea and fatigue, grade 3 < 10%. Molecular analyses identified different mechanisms of PARPi resistance in ~77% of evaluable pts with matched pre-post PARPi progression biopsies such as reversion mutations in BRCA1/2 and other homologous repair (HR) genes; BRCA, HR and MDR upregulation, CCNE amplification and RIG-I like receptor downregulation. Conclusions: Treatment with olaparib-cediranib after PARPi failure was feasible and met the predefined bar for efficacy in each cohort. This is the largest clinical trial prospectively evaluating PARPi failure and correlating tissue genomic mechanisms of resistance. Clinical trial information: NCT02681237.

Gefitinib plus celecoxib in chemotherapy-naïve patients with stage IIIB/IV non-small cell lung cancer (NSCLC): A phase II study from the Hoosier Oncology Group

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7066-7066 ◽  
Author(s):  
A. K. Agarwala ◽  
L. Einhorn ◽  
W. Fisher ◽  
D. Bruetman ◽  
J. McClean ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Day Treatment ◽  
Single Agent ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Stage Iiib ◽  
Never Smokers ◽  
Ecog Ps

7066 Background: Gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR) pathway, has single agent activity in NSCLC. Preclinical studies demonstrate significant interactions between the EGFR and cyclo-oxygenase 2 (COX-2) pathways and that simultaneous inhibition against NSCLC may have benefits over gefitinib alone. Methods: Eligibility required that pts were chemotherapy-naïve, had stage IIIb (with pleural effusion) or IV NSCLC and an ECOG PS 0–1. Pts received gefitinib 250mg orally daily plus celecoxib 400mg orally every 12 hours. Cycles consisted of 21 day treatment and continued until unacceptable toxicity or progression of disease. The primary objective of this single arm, two-stage, phase II study was to evaluate the overall response rate. If ≤ 10 out of 30 pts achieved a complete (CR) or partial response (PR), the study would be stopped early. If >10 out of 30 pts had a CR or PR, enrollment would continue to 50 pts. Results: From 1/04 to 11/04, 31 pts were enrolled: male/female 13/18; median age 70.8 years (range, 19–93); 67.7% had adenocarcinoma; ECOG PS 0/1 13/18; stage IIIb/IV 2/29; 5 were current smokers, 9 were remote (>30 years) or never smokers, 16 quit smoking > 3 months ago. Median number of cycles was 4 (range, 0–16). 6 pts (19.4%) discontinued therapy due to toxicity, including 3 who died due to treatment. Select grade 3/4 toxicities included: pulmonary (6.5%), hepatic (6.5%), diarrhea (6.5%), skin (3.2%). Responses included PR 5 (16.1%), stable disease 8 (25.8%), and progressive disease 18 (58.1%). Median duration of response, progression free survival, and overall survival was 5.7, 2.8, and 7.2 months, respectively. All responders were females with adenocarcinoma, 2 were remote or never smokers and 3 were former smokers. Conclusion: Gefitinib plus celecoxib in an unselected population of chemotherapy naïve patients with advanced NSCLC and a PS of 0–1 has a lower response rate and overall efficacy compared with historical controls of chemotherapy. [Table: see text]

Phase II trial of single-agent ganetespib (STA-9090), a heat shock protein 90 (Hsp90) inhibitor in heavily pretreated patients with metastatic castration-resistant prostate cancer (mCRPC) post docetaxel-based chemotherapy: Results of a Prostate Cancer Clinical Trials Consortium (PCCTC) study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5085-5085 ◽  
Author(s):  
Elisabeth I. Heath ◽  
Mark N. Stein ◽  
Ulka N. Vaishampayan ◽  
Emmanuel S. Antonarakis ◽  
Glenn Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Cancer Cells ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Stage 1

5085 Background: Hsp90 is a molecular chaperone required for the proper folding and activation of numerous client proteins and is critical to cell survival and proliferation. Ganetespib (G), a synthetic small molecule that binds to the ATP pocket in the N-terminus of Hsp90 causes the degradation of cellular proteins and ultimately death of cancer cells dependent on these proteins. G displays potent anticancer activity in prostate cancer cells. Methods: Eligible patients were ≥ 18 yrs old with ECOG performance status ≤ 2. Adequate hepatic, renal, and bone marrow function was required. Patients were treated with G 200 mg/m2 intravenously once weekly for 3 consecutive weeks followed by 1 off-week. The primary objective was to evaluate the 6-month progression-free survival (PFS). Secondary endpoints included overall safety and tolerability of G and overall survival. Exploratory markers including maspin, cytokeratins 8 and 18, and HDAC1 were obtained pre, during, and post G treatment. We sought ≥ 4 patients with ≥ 6 months PFS (a success) in Stage 1 of a 2-stage near-optimal Simon design. Results: 18 patients were enrolled at 4 institutions. The patients’ median age was 68 (range 51-82), 13 were Caucasian, 4 were African American, and 1 was Asian. Median PSA was 210.7 ng/mL (range 25.9 – 3,489 ng/mL). One patient never started therapy. Among the 17 treated patients, the median number of cycles was 2 (range 1-5). The most frequent Grade 3 toxicities were diarrhea (3 patients), fatigue (3), and dehydration (3). Prior therapy included abiraterone (8), sipuleucel-T (4), and other targeted therapy (4). With < 4 successes in Stage 1, the trial was terminated early. Median PFS was 1.9 months (90% CI: 1.7 – 2.7 months); median OS was 10.2 months (90% CI: 2.3 – 18.3 months). Exploratory markers have been evaluated and will be presented. Conclusions: Our study represents the first clinical trial of G in treating mCRPC patients. As a single agent therapy, G did not prolong PFS. Combination therapy is a consideration to improve therapeutic efficacy. Clinical trial information: NCT01270880.

Phase II trial of carboplatin plus cetuximab for the treatment of stage IIIB/IV non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18005-18005 ◽  
Author(s):  
D. S. Bradford ◽  
M. A. Socinski ◽  
R. V. LaRocca ◽  
T. A. Hensing ◽  
R. E. Bordoni
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Stage Iiib ◽  
Open Label ◽  
Igg1 Monoclonal Antibody

18005 Background: Cetuximab, an IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR) on both normal and tumor cells, has been investigated in advanced NSCLC as a single agent and in combination with chemotherapy. At the time of study design, triplet therapy had not demonstrated activity greater than doublets. This ongoing phase II open-label trial evaluates the doublet of cetuximab in combination with carboplatin (Cb) in patients (pts) with previously untreated stage IIIB/IV NSCLC. Methods: Eligible pts receive cetuximab 400 mg/m2 IV on day 1. Starting on day 8, pts receive cetuximab 250 mg/m2 IV weekly plus Cb AUC=6 IV q3w for 4 cycles (12 weeks). Pts who achieve CR, PR, or SD after 4 cycles may continue weekly cetuximab monotherapy until disease progression or unacceptable toxicity. The primary objective is to evaluate the response rate. Secondary objectives are to determine median progression-free survival (PFS) at 6 months and median overall survival (OS) at 1 year. Results: The study has completed accrual, enrolling and treating 57 pts, all evaluable for response. None had received prior adjuvant chemotherapy for NSCLC. All pts received cetuximab; 49 received Cb. Of the 57 pts, 55 have discontinued: 30 (52.6%) for disease progression or relapse. Drug-related adverse events occurred in 53 pts (93%). Conclusions: These preliminary data of cetuximab in combination with Cb demonstrated modest response rates with an acceptable toxicity profile in pts with advanced NSCLC. Final PFS and OS data are pending. [Table: see text] No significant financial relationships to disclose.

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