Palbociclib plus cetuximab versus placebo plus cetuximab in platinum-resistant, cetuximab-naive, HPV-unrelated head and neck cancer: A double-blind randomized phase II trial (PALATINUS).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6013-6013 ◽  
Author(s):  
Douglas Adkins ◽  
Jin-Ching Lin ◽  
Assuntina Gesualda Sacco ◽  
Jessica C. Ley ◽  
Peter Oppelt ◽  
...  
Keyword(s):  
Head And Neck ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Rank Test ◽  
Double Blind ◽  
Platinum Resistant ◽  
Randomized Phase Ii

6013 Background: Cetuximab monotherapy results in a median overall survival (OS) of approximately 6 months (mo) in platinum-resistant recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). HNSCC unrelated to human papillomavirus (HPV) is driven by hyperactivation of the CDK4/6 and cyclin D1 (CD1) regulatory complex, resulting in cell cycle progression and tumor growth, suggesting that CDK4/6 inhibition can be a rational therapeutic strategy in this setting. Palbociclib (PAL) is a selective CDK4/6 inhibitor that may reverse cetuximab resistance by countering the actions of deregulated CD1. PAL plus an epidermal growth factor receptor inhibitor synergistically reduced cell viability of HPV-unrelated HNSCC cell lines. In a single-arm, multicenter trial of platinum-resistant, cetuximab-naive, HPV-unrelated HNSCC, PAL in combination with cetuximab resulted in a median OS of 9.5 mo. Methods: In a double-blind randomized phase II trial, patients (pts) with platinum-resistant, cetuximab-naïve, HPV-unrelated HNSCC were treated with cetuximab plus either PAL (arm A) or placebo (arm B). Pts were stratified by performance status (PS) and prior immunotherapy (IT). 120 pts were required for 1:1 randomization to have ≥ 80% power to detect a hazard ratio (HR) of 0.6 (corresponding to a median OS of 10 mo in arm A and 6 mo in arm B) using a 1-sided log-rank test P=0.10). Key secondary endpoints included progression-free survival (PFS), adverse events (AEs), and p16 status. Results: Pts (n=125) were randomized (arm A, 65; arm B, 60). PS and prior IT were balanced between the arms. Median (95% CI) follow-up for OS was 15.9 (15.0–19.4) mo. Median OS was 9.7 (7.3–13.9) mo in arm A and 7.8 (6.7–10.6) mo in Arm B (stratified by PS: HR=0.82 [95% CI, 0.54–1.25], P=0.18). Median PFS was 3.9 mo in arm A and 4.6 mo in arm B (stratified by PS: HR=1.00 [0.7–1.5], P=0.5). Hematologic AEs were more common in arm A. Only 11 pts (9%) received IT after being treated on the trial. Conclusions: Among pts with platinum-resistant, HPV-unrelated HNSCC, PAL plus cetuximab resulted in a trend of prolongation of median OS compared with cetuximab. Clinical trial information: NCT02499120.

A randomized phase II trial of weekly docetaxel plus either cisplatin or oxaliplatin in patients with previously untreated advanced gastric cancer: Preliminary results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4566-4566
Author(s):  
S. Sym ◽  
S. Park ◽  
J. Park ◽  
K. Kwon ◽  
I. Jung ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tolerability Profile ◽  
Preliminary Results ◽  
Weekly Docetaxel ◽  
Randomized Phase Ii ◽  
Significant Difference

4566 Background: Docetaxel, in combination with cisplatin or oxaliplatin, has demonstrated efficacy against AGC. This randomized phase II trial evaluated two weekly docetaxel-based regimens to see which would be most promising according to objective response rate (ORR) as first-line therapy in AGC. Methods: Chemotherapy-naïve patients with measurable unresectable and/or metastatic gastric adenocarcinoma and a performance status ≤2 were randomly assigned to receive docetaxel (35 mg/m2) weekly on days 1 and 8 of a 21-day cycle plus either cisplatin (60 mg/m2 on day 1) (arm A) or oxaliplatin (120 mg/m2 on day 1) (arm B). Toxicity was assessed on days 1, 8, and 21 of each cycle, and response was evaluated every 2 cycles. Results: Between March 2007 and December 2008, 61 eligible patients entered. In Arm A, 29 patients were evaluable for objective response and 31 for safety. In Arm B, 28 patients were evaluable for objective response and 30 for safety. Median age was 52 years and disease status was comparable for both arms. Ten of 29 (34.5%) patients had a confirmed objective response in the arm A (95% confidence interval [CI] 17.1–51.8%) and 11 of 28 (39.2%) patients had a confirmed objective response in the arm B (95% CI 21.1- 57.2%). No significant difference was noted between the arms both for ORR (p=0.202) or for disease control (58.6% and 82.1%, respectively, p=0.082). Median progression free survival time was 4.4 month in the arm A and 4.3 months in the arm B (Hazard ratio = 0.936; 95% CI, 0.503–1.744; p = 0.836). There was no relevant difference in the occurrence of overall grade ¾ toxicity between the two arms (51.6% vs. 46.6%, respectively; p=0.800). Neutropenia was the most common grade 3/4 toxicity (32.3% vs. 36.6%, respectively). There was one treatment related death in Arm B. Conclusions: The preliminary results showed that both treatment arms have similar clinical efficacy as front-line treatment in AGC. Each regimen has a manageable tolerability profile. The accrual is ongoing. No significant financial relationships to disclose.

Randomized phase II trial of single agent erlotinib vs. standard chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and performance status (PS) of 2

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7022-7022 ◽  
Author(s):  
R. Lilenbaum ◽  
R. Axerold ◽  
S. Thomas ◽  
A. Dowlati ◽  
L. Seigel ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Single Agent ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Initial Therapy ◽  
Randomized Phase Ii ◽  
Never Smokers ◽  
And Performance

7022 Background: A previous CALGB trial suggested a benefit for carboplatin-paclitaxel (CP) over P alone in pts with PS 2. Erlotinib (E) has activity in previously treated pts with low PS but has not been formally tested in 1st line. Methods: In a multi-center randomized phase II trial, untreated pts with advanced NSCLC and PS 2 were randomized to E 150 mg daily or CP (AUC 6 and 200 mg/m2) for 4 cycles. Pts in CP who progressed, did not tolerate, or refused further therapy were allowed to cross over to E. The primary endpoint was progression-free survival (PFS). QoL analysis was performed in all pts and tumor samples were obtained whenever possible. Results: As of 12/05, 98 of 102 projected pts have been accrued. Results are reported for 88 (46 E; 42 CP). Demographics were balanced except for more females in E (59%) than CP (45%). Most pts had stage IV adenoca histology. Never-smokers comprised 13% and 7% of pts respectively. Response for E: 2% PR and 30% SD; for CP, 10% PR and 45% SD. Gr 2–4 toxicities for E: rash (34%) and diarrhea (11%); for CP: nausea (12%), neuropathy (14%) and fatigue (29%). Median PFS was 2.5 mo for E (95%CI 1.28 - 2.79) and 4.0 mo for CP (95%CI 2.66 - 4.86). Of 42 pts in CP, 21 have crossed over to E. Conclusions: This is the first randomized phase II trial of E in PS 2 patients. Based on preliminary results, PS 2 patients seemed to fare better with standard CP than single agent E as initial therapy. Mature survival and QoL data will be available in June. [Table: see text]

Final analysis of a multi-center, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin (GC) plus bevacizumab (B) or placebo (P) in patients (pts) with malignant mesothelioma (MM)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7526-7526 ◽  
Author(s):  
T. Karrison ◽  
H. L. Kindler ◽  
D. R. Gandara ◽  
C. Lu ◽  
T. L. Guterz ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Ii Trials ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Randomized Phase Ii ◽  
Major Vessel ◽  
Grade 3

7526 Background: In phase II trials in MM, GC on a 21-day (D) schedule has response rates of 16%–26% and median overall survival (OS) of 9.6–13 months (mo). Since VEGF has a key role in MM biology, we added anti-VEGF antibody B to GC in a multi-center, double- blind, placebo-controlled randomized phase II trial. Methods: Eligible pts had unresectable MM; no prior chemotherapy; PS 0–1; no thrombosis, bleeding, or major vessel invasion. Primary endpoint: progression-free survival (PFS). Statistics: 90% power to detect HR 0.57. Stratification: PS (0/1), histology (epithelial/other). G 1,250 mg/m2 D 1, 8 Q21D, C 75 mg/m2 D1 Q21D, and B 15 mg/kg or P D1 Q21D was given × 6 cycles, then B or P Q21D until progression. Baseline plasma VEGF was measured. 115 pts enrolled 12/01- 07/05 at 11 sites, 108 (GCB/GCP) 53/55 were evaluable. Male 74%/84%; median age 62/65 (range 44–78/20–84); PS 1 55%/47%; epithelial 74%/67%; pleural 93%/91%; thrombocytosis 40%/40%. Results: Cycles: total 458/424, median 7/6, range 1–42/2–39. Statistically significantly different (SSD) toxicity (p <0.05), any grade: alopecia 60%/38%; epistaxis 62%/24%; hypertension 45%/22%; non-neutropenic infection 15%/4%; proteinuria 62%/47%; stomatitis 23%/7%. There were no SSD toxicities = grade 3. Median PFS 6.9/6.0 mo (HR 0.93, p=0.88). Median OS 15.6/14.7 mo (p=0.91). 1-year survival 59%/57%. Partial response 25%/22%; stable disease 51%/60%. Median VEGF (N=56) 131/154 pg/ml (range 31–1760/5–1786). Higher VEGF was associated with shorter PFS (p=0.02) and OS (p=0.0066). In pts with VEGF = the median, PFS (p=0.043) and OS (p=0.028) were significantly greater for GCB than GCP; in high VEGF strata this was not SSD. Conclusion: Adding B to GC in MM pts does not yield statistically significant differences in PFS, OS, response, or grade ¾ toxicity. GCB-treated pts with low VEGF levels had longer PFS and OS. Supported by NCI grant N01-CM-17102. No significant financial relationships to disclose.

Irinotecan, cetuximab, and bevacizumab (CBI) versus irinotecan, cetuximab, and placebo (CI) in irinotecan-refractory metastatic colorectal cancer (mCRC): Results from an ACCRU network randomized phase II trial.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 102-102
Author(s):  
Marla Lipsyc-Sharf ◽  
Fang-Shu Ou ◽  
Matthew B. Yurgelun ◽  
Douglas Adam Rubinson ◽  
Deborah Schrag ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Double Blind ◽  
Cox Proportional Hazard Models ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Line Of Therapy

102 Background: Combination irinotecan and cetuximab is approved for irinotecan-refractory mCRC; it is unknown if the addition of bevacizumab would improve outcomes. We studied the efficacy and safety of CBI compared with CI in patients (pts) with RAS wildtype, irinotecan-refractory mCRC. Methods: In this multicenter, randomized, double-blind, placebo-controlled phase II trial, pts with RAS wildtype mCRC and no prior anti-epidermal growth factor receptor therapy who failed at least 1 irinotecan-based chemotherapy regimen and received bevacizumab in at least 1 prior line of therapy were randomized 1:1 to irinotecan 180 mg/m2 (or previously tolerated dose), cetuximab 500 mg/m2, and bevacizumab 5 mg/kg vs CI every 2 wks until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoint was progression free survival (PFS). Multivariable Cox proportional hazard models stratified by number of prior lines of therapy and bevacizumab receipt in immediate prior line were performed. Secondary endpoints included overall survival (OS), objective response rate (ORR), and adverse events (AEs). The study was closed early in January 2018 for reasons related to accrual and funding after enrollment of 36 out of a planned 60 pts. Results: Between July 2015 and December 2017, 36 pts were randomized (19 to CBI, 17 to CI). 34 pts (94%) were treated with 2 or more prior chemotherapy regimens. Baseline characteristics were similar between arms. Median PFS was 9.7 vs 5.5 mo for CBI and CI arms, respectively (log-rank P =0.76; multivariable HR = 0.64; 95% CI, 0.25-1.66). Median OS was 19.7 vs 10.2 mo for CBI and CI (log-rank P= 0.04; multivariable HR = 0.41; 95% CI, 0.15-1.09). ORR was 37% for CBI vs 12% for CI ( P =0.13). Grade 3 or higher AEs occurred in 47% of pts receiving CBI vs 35% for CI ( P =0.46). Conclusions: In this prematurely discontinued trial, there were non-significant increases in PFS and ORR and a statistically significant 9.5 mo increase in median OS in favor of CBI compared to CI. Further investigation of CBI for treatment of irinotecan-refractory mCRC is warranted. Clinical trial information: NCT02292758.

Targeting IGF-1/2 with xentuzumab (Xe) plus enzalutamide (En) in metastatic castration-resistant prostate cancer (mCRPC) after progression on docetaxel chemotherapy (DCt) and abiraterone (Abi): Randomized phase II trial results.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5030-5030 ◽  
Author(s):  
Syed A. Hussain ◽  
Pablo Maroto ◽  
Miguel Ángel Climent ◽  
Diletta Bianchini ◽  
Robert Hugh Jones ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Specific Antigen ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Neutralizing Antibody ◽  
Endocrine Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Randomized Phase Ii ◽  
Ecog Ps

5030 Background: Insulin-like growth factor receptor-1 (IGF-1R) signaling activates the PI3K/AKT pathway and may lead to androgen receptor (AR) transactivation and progression to endocrine treatment resistance. Xe, an IGF-ligand-neutralizing antibody, binds to IGF-1 and IGF-2 and inhibits IGF-1R signaling. This multi-center randomized phase II trial (NCT02204072) evaluated anti-tumor activity of Xe plus En in mCRPC. Methods: Men with histologically/cytologically confirmed mCRPC and progression after DCt+Abi were randomized to receive Xe 1000mg IV QW + En 160mg/day oral, or En alone (28-day cycles until progression or intolerable adverse events [AEs]). Primary endpoint: progression-free survival by investigator assessment (PFS-IA); secondary: PFS by central review (PFS-CR), overall survival (OS), AEs. Results: Overall, 43 patients were randomized per arm; 70% Caucasian and 29% Asian (median age 70 y; range 46–88). At baseline (BL) the two arms were generally well balanced, although 33% v 47% were ECOG PS O, and 72% v 56% had a Gleason total score ≥8. By data cut-off (23 October 2017), 39/43 (Xe+En) and 38/43 patients (En) had discontinued, most due to disease progression. The median PFS-IA was 7.4 m for Xe+En (95% CI: 3.5–8.7) and 6.2 m for En (3.5–11.1) [HR = 0.99 (0.56–1.73); p = 0.96]. The results were similar after adjusting for BL ECOG PS and Gleason score. The median PFS-CR was 3.6 m for Xe+En (3.5–8.1) and 6.2 m for En (3.6–8.3) (HR = 1.22 [0.70–2.13]; p = 0.48). OS data are immature. For the two arms, prostate-specific antigen (PSA) response rates were 21% and 19%; maximum decline in PSA: -20 v -9 μg/L; PSA change at week 12: 19% v 18%; maximum decline in circulating tumor cells (CTC): -52% v -35%; and CTC response: 16% v 11%. The most frequently reported AEs were: fatigue 67% v 49%; decreased appetite 56% v 54%; weight reduction 37% v 12%; anemia 33% v 44%; back pain 30% v 37%. Nine patients discontinued Xe due to AEs. Conclusions: Addition of Xe to En did not prolong PFS in mCRPC compared with En alone. There were no notable differences in PSA-related endpoints and CTC between arms. Clinical trial information: NCT02204072.

scholarly journals Multicenter, Double-Blind, Placebo-Controlled, Randomized Phase II Trial of Gemcitabine/Cisplatin Plus Bevacizumab or Placebo in Patients With Malignant Mesothelioma

2012 ◽  
Vol 30 (20) ◽  
pp. 2509-2515 ◽  
Author(s):  
Hedy L. Kindler ◽  
Theodore G. Karrison ◽  
David R. Gandara ◽  
Charles Lu ◽  
Lee M. Krug ◽  
...  
Keyword(s):  
Phase Ii ◽  
Malignant Mesothelioma ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Phase Ii Trials ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Histologic Subtype ◽  
Double Blind Placebo ◽  
Randomized Phase Ii

PurposeGemcitabine plus cisplatin is active in malignant mesothelioma (MM), although single-arm phase II trials have reported variable outcomes. Vascular endothelial growth factor (VEGF) inhibitors have activity against MM in preclinical models. We added the anti-VEGF antibody bevacizumab to gemcitabine/cisplatin in a multicenter, double-blind, placebo-controlled randomized phase II trial in patients with previously untreated, unresectable MM.Patients and MethodsEligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 and no thrombosis, bleeding, or major blood vessel invasion. The primary end point was progression-free survival (PFS). Patients were stratified by ECOG performance status (0 v 1) and histologic subtype (epithelial v other). Patients received gemcitabine 1,250 mg/m2on days 1 and 8 every 21 days, cisplatin 75 mg/m2every 21 days, and bevacizumab 15 mg/kg or placebo every 21 days for six cycles, and then bevacizumab or placebo every 21 days until progression.ResultsOne hundred fifteen patients were enrolled at 11 sites; 108 patients were evaluable. Median PFS time was 6.9 months for the bevacizumab arm and 6.0 months for the placebo arm (P = .88). Median overall survival (OS) times were 15.6 and 14.7 months in the bevacizumab and placebo arms, respectively (P = .91). Partial response rates were similar (24.5% for bevacizumab v 21.8% for placebo; P = .74). A higher pretreatment plasma VEGF concentration (n = 56) was associated with shorter PFS (P = .02) and OS (P = .0066), independent of treatment arm. There were no statistically significant differences in toxicity of grade 3 or greater.ConclusionThe addition of bevacizumab to gemcitabine/cisplatin in this trial did not significantly improve PFS or OS in patients with advanced MM.

PRECEDENT: A Randomized Phase II Trial Comparing Vintafolide (EC145) and Pegylated Liposomal Doxorubicin (PLD) in Combination Versus PLD Alone in Patients With Platinum-Resistant Ovarian Cancer

2013 ◽  
Vol 31 (35) ◽  
pp. 4400-4406 ◽  
Author(s):  
R. Wendel Naumann ◽  
Robert L. Coleman ◽  
Robert A. Burger ◽  
Edward A. Sausville ◽  
Elzbieta Kutarska ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Phase Ii Trial ◽  
Folate Receptor ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Platinum Resistant ◽  
Randomized Phase Ii

Purpose Vintafolide (EC145) is a folic acid–desacetylvinblastine conjugate that binds to the folate receptor (FR), which is expressed on the majority of epithelial ovarian cancers. This randomized phase II trial evaluated vintafolide combined with pegylated liposomal doxorubicin (PLD) compared with PLD alone. The utility of an FR-targeted imaging agent, 99mTc-etarfolatide (EC20), in selecting patients likely to benefit from vintafolide was also examined. Patients and Methods Women with recurrent platinum-resistant ovarian cancer who had undergone ≤ two prior cytotoxic regimens were randomly assigned at a 2:1 ratio to PLD (50 mg/m2 intravenously [IV] once every 28 days) with or without vintafolide (2.5 mg IV three times per week during weeks 1 and 3). Etarfolatide scanning was optional. The primary objective was to compare progression-free survival (PFS) between the groups. Results The intent-to-treat population comprised 149 patients. Median PFS was 5.0 and 2.7 months for the vintafolide plus PLD and PLD-alone arms, respectively (hazard ratio [HR], 0.63; 95% CI, 0.41 to 0.96; P = .031). The greatest benefit was observed in patients with 100% of lesions positive for FR, with median PFS of 5.5 compared with 1.5 months for PLD alone (HR, 0.38; 95% CI, 0.17 to 0.85; P = .013). The group of patients with FR-positive disease (10% to 90%) experienced some PFS improvement (HR, 0.873), whereas patients with disease that did not express FR experienced no PFS benefit (HR, 1.806). Conclusion Vintafolide plus PLD is the first combination to demonstrate an improvement over standard therapy in a randomized trial of patients with platinum-resistant ovarian cancer. Etarfolatide can identify patients likely to benefit from vintafolide.

Paclitaxel Given Once Per Week With or Without Bevacizumab in Patients With Advanced Angiosarcoma: A Randomized Phase II Trial

2015 ◽  
Vol 33 (25) ◽  
pp. 2797-2802 ◽  
Author(s):  
Isabelle L. Ray-Coquard ◽  
Julien Domont ◽  
Emmanuelle Tresch-Bruneel ◽  
Emmanuelle Bompas ◽  
Philippe A. Cassier ◽  
...  
Keyword(s):  
Phase Ii ◽  
De Novo ◽  
Phase Ii Trial ◽  
Clinical Investigation ◽  
Performance Status ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Randomized Phase Ii ◽  
Radiation Induced

Purpose The aim of this randomized, phase II trial was to explore the activity and safety of adding bevacizumab to paclitaxel once per week in treatment of angiosarcomas (AS). Methods Patients were treated with paclitaxel alone (90 mg/m2 per week for six cycles of 28 days each; arm A) or with paclitaxel combined with bevacizumab (10 mg/kg once every 2 weeks; arm B). In the combination treatment arm, bevacizumab was administered after the six cycles of chemotherapy as maintenance therapy (15 mg/kg once every 3 weeks) until intolerance or progression occurred. Stratification factors were superficial versus visceral AS and de novo versus radiation-induced AS. The primary end point was the 6-month progression-free survival (PFS) rate, which was based on RECIST, version 1.1. Statistical assumptions were P0 = 20%, P1 = 40%, a = 10%, and b = 20%. P0 was the PFS rate at 6 months defining inactive drug, and P1 was the PFS rate at 6 months defining promising drug. Results A total of 52 patients were enrolled, and 50 were randomly assigned in 14 centers. The most common primary sites were the breast (49%) and skin (12%). There were 17 (34%) visceral and 24 (49%) radiation-induced AS. The performance status was 0 in 24 patients (49%) and 1 in the remaining 25 patients (51%). The median follow-up time was 14.5 months. Both treatment regimens were considered active, with 6-month PFS rates of 54% (14 of 26) in arm A and 57% (14 of 24) in arm B. The median overall survival rates were 19.5 months in arm A and 15.9 months in arm B. Toxicity was higher with the combination arm and included one fatal drug-related toxicity (intestinal occlusion). Conclusion The primary objective was met in both treatment arms. However, the present data do not support additional clinical investigation of combined paclitaxel/bevacizumab for the treatment of advanced AS.

Sorafenib (S) alone versus S combined with gemcitabine and oxaliplatin (GEMOX) in first-line treatment of advanced hepatocellular carcinoma (HCC): Final analysis of the randomized phase II GONEXT trial (UNICANCER/FFCD PRODIGE 10 trial).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4028-4028 ◽  
Author(s):  
Eric Assenat ◽  
Valerie Boige ◽  
Simon Thézenas ◽  
Georges-Philippe Pageaux ◽  
Jean-Marie Peron ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Advanced Hepatocellular Carcinoma ◽  
Randomized Phase Ii ◽  
Grade 3

4028 Background: HCC is a vascular tumor with poor prognosis. Although S has been shown to improve survival, its ability to induce tumor shrinkage is very low. Given the activity of Gemcitabine and Oxaliplatin (GEMOX) in HCC, a phase II trial combining S with GEMOX was undertaken to define efficacy and safety profile. Methods: Patients with inoperable advanced and/or metastatic HCC (BCLCC B or C), with or without prior palliative chemoembolization, Child pugh score A, WHO performance status (PS) 0-1, were eligible for this two-stage, randomized phase II trial. Patients received S (400 mg BID) alone (arm A) or in combination with GEMOX every 2 weeks (gem. 1000 mg/m² [10 mg/m²/min] on D1; oxaliplatin, 100 mg/m² on D2) (arm B). Randomization was stratified according to CLIP score (0-1 vs. 2-3) and center. Primary endpoint was crude 4-mo Progression-Free Survival (PFS) rate (H0, < 50%; H1, ≥ 70%; α = 10%; 1- β= 90%). Results: From Dec 2008 to Oct. 2011, 94 pts were enrolled: median age, 64 yrs; male, 88%; PS 0 (69%) 1(31%), CLIP 0-1 (48%) 2-3 (52%), cirrhosis (63%), portal vein thrombosis (29%), extra liver metastasis (69%). These characteristics were well balanced in both arms. Median duration and dose intensity of S were 4 mo (1-27) and 81% in both arms, respectively. Median number of GEMOX cycles was 7 (1-12) in arm B. Main severe (grade 3-4) toxicity (arm A/B) consisted of neutropenia (grade 3-4: 0%/7%), fatigue (18%/24%), thrombocytopenia (0%/9%), diarrhea (grade 2-4: 10%/21%), peripheral neuropathy (grade 2-3: 0%/10%), and hand foot syndrome (grade 2-3: 13%/7%). For evaluable pts (n = 83), ORR was 9% / 16% and DCR was 70%/77% in arms A/B, respectively. For all pts (median follow-up, 17.6 mo), 4-mo PFS rate was 54%/61%, median PFS was 4.6 (3.9-6.2)/6.2 (3.8-6.8) mo, and median OS was 13.0 (10.4-22.2) /13.5 (7.5-19.1) mo in arms A/B, respectively. Conclusions: S plus GEMOX was feasible in HCC. This trial met its primary endpoint (4-mo PFS ≥ 50%) and ORR, median PFS and OS were encouraging data. Exploratory analyses are underway to identify subgroups of patients likely to derive most benefit from this combination. Clinical trial information: NCT00941967.

scholarly journals Randomized Phase II Trial of Seribantumab in Combination With Paclitaxel in Patients With Advanced Platinum-Resistant or -Refractory Ovarian Cancer

2016 ◽  
Vol 34 (36) ◽  
pp. 4345-4353 ◽  
Author(s):  
Joyce F. Liu ◽  
Isabelle Ray-Coquard ◽  
Frederic Selle ◽  
Andrés M. Poveda ◽  
David Cibula ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Open Label ◽  
Treatment Benefit ◽  
Peritoneal Cancer ◽  
Platinum Resistant ◽  
Randomized Phase Ii ◽  
Intent To Treat

Purpose Seribantumab is a fully human immunoglobulin G2 monoclonal antibody that binds to human epidermal growth factor receptor (HER) 3 (ErbB3), blocking heregulin (HRG) –mediated ErbB3 signaling and inducing ErbB3 receptor downregulation. This open-label randomized phase II study evaluated progression-free survival (PFS) with seribantumab in combination with once-per-week paclitaxel compared with paclitaxel alone in patients with platinum-resistant or -refractory ovarian cancer. A key secondary objective was to determine if any of five prespecified biomarkers predicted benefit from seribantumab. Patients and Methods Patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomly assigned at a ratio of two to one to receive seribantumab plus paclitaxel or paclitaxel alone. Patients underwent pretreatment core needle biopsy; archival tumor samples were also obtained to support biomarker analyses. Results A total of 223 patients were randomly assigned (seribantumab plus paclitaxel, n = 140; paclitaxel alone, n = 83). Median PFS in the unselected intent-to-treat population was 3.75 months with seribantumab plus paclitaxel compared with 3.68 months with paclitaxel alone (hazard ratio [HR], 1.027; 95% CI, 0.741 to 1.425; P = .864). Among patients whose tumors had detectable HRG mRNA and low HER2 (n = 57 [38%] of 151 with available biomarker data), increased treatment benefit was observed in those receiving seribantumab plus paclitaxel compared with paclitaxel alone (PFS HR, 0.37; 95% CI, 0.18 to 0.76; P = .007). The HR in patients not meeting these criteria was 1.80 (95% CI, 1.08 to 2.98; P = .023). Conclusion The addition of seribantumab to paclitaxel did not result in improved PFS in unselected patients. Exploratory analyses suggest that detectable HRG and low HER2, biomarkers that link directly to the mechanism of action of seribantumab, identified patients who might benefit from this combination. Future clinical trials are needed to validate this finding and should preselect for HRG expression and focus on cancers with low HER2 levels.

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