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.

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.

TRYHARD, a randomized phase II trial (RTOG Foundation 3501) of concurrent accelerated radiation plus cisplatin (cis) with or without lapatinib (Lap) for stage III- IV Non-HPV head and neck carcinoma (HNC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6014-6014
Author(s):  
Stuart J. Wong ◽  
Pedro A. Torres-Saavedra ◽  
Nabil F. Saba ◽  
George Shenouda ◽  
Jeffrey Bumpous ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Stage Iii ◽  
Adverse Event Rate ◽  
Rank Test ◽  
Days Of Therapy ◽  
Grade 3

6014 Background: Chemoradiation (CRT) with cis or anti-EGFR Ab has been shown to improve survival of patients with stage III-IV HNC. Since Lap, a dual EGFR and HER2 inhibitor, has shown effectiveness with CRT in a pilot non-HPV HNC cohort, the RTOG Foundation launched a phase II trial to test the hypothesis that adding Lap to the RT-cis for frontline therapy of stage III-IV Non-HPV HNC improves progression-free survival (PFS). Methods: Patients with stage III-IV carcinoma of the oropharynx (p16-negative), larynx, and hypopharynx, having Zubrod performance of 0-1, and meeting predefined blood chemistry criteria were enrolled after providing consent. Patients were randomized (1:1) to 70 Gy (6 weeks) + 2 cycles of CDDP (q3 weeks) plus either Lap (1500 mg daily, Arm A) or placebo (Arm B) starting 1 week prior to RT and concurrent with RT and for 3 months post RT. PFS was the primary endpoint. The protocol specified 69 PFS events (142 patients) for the final analysis based on HR = 0.65, 80% power, 1-sided alpha 0.20, and one interim efficacy and futility analysis at 50% information. PFS rates between arms for all randomized patients were compared by 1-sided log-rank test (1-sided alpha 0.1803). Overall survival (OS) was a secondary endpoint. Results: From 10/’12 to 04/’17, 142 patients were enrolled, of whom 127 were randomized, 63 to Arm A and 64 to Arm B. Arms A vs B, respectively, were similar in baseline patient characteristics, radiation delivery, completing ≥ 70 Gy (85.7% vs. 82.8%) and cisplatin delivery, completing 200 (±5%) mg/m2 (65.1% vs 70.3%), but dissimilar in Lap/placebo delivery (median dose, 87000 mg vs. 125250 mg). Median follow-up was 4.1 years for surviving patients. The final analysis suggests no improvement in PFS of adding Lap to CRT (HR [A/B]: 0.91, 95% confidence interval CI 0.56-1.46; P= 0.34; 2-year rates: 50.6%, CI 37.5-63.7% vs. 56.2% CI 43.0-69.4%), or in OS (HR: 1.06, CI 0.61-1.86; P = 0.58; 2-year rates: 71.8% CI 60.1-83.5% vs. 76% CI 64.5-87.4%), death within 30 days of therapy (3.3% vs. 3.4%), and overall treatment-related grade 3-5 adverse event rate (86.7% vs. 84.7%). Grade 3-4 mucositis rates on Arm A and Arm B were 21.7% vs. 23.7%, all grade dysphagia and rash rates were 43.3% vs. 59.3%, and 13.3% vs. 6.8%, respectively. Conclusions: The addition of Lap to the radiation-cisplatin platform did not improve progression-free or overall survival in unselected non-HPV HN. Thus, dual EGFR, HER-2 inhibition does not appear to enhance the effects of chemoradiation. Although we showed that accrual to a non-HPV HN specific trial is feasible, new strategies must be investigated to improve the outcome for this poor prognosis HN population.

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.

Gemcitabine and oxaliplatin (GEMOX) alone or in combination with cetuximab as first-line treatment for advanced biliary cancer: Final analysis of a randomized phase II trial (BINGO).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4032-4032 ◽  
Author(s):  
David Malka ◽  
Laetitia Fartoux ◽  
Vanessa Rousseau ◽  
Tanja Trarbach ◽  
Eveline Boucher ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Mutational Analysis ◽  
Metabolic Response ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
First Line ◽  
Open Label ◽  
Randomized Phase Ii

4032 Background: Gemcitabine-platinum chemotherapy (CTx) regimens are widely accepted as first-line standard of care for patients (pts) with advanced biliary cancers (ABC). EGFR overexpression has been observed in ABC, suggesting that the combination with anti-EGFR monoclonal antibodies may be appropriate. Methods: Patients with ABC, WHO performance status (PS) 0-1, and without prior palliative CTx were eligible for this international, open-label, two-stage, non-comparative, randomized phase II trial. Patients received GEMOX (gemcitabine, 1 g/m² [10 mg/m²/min] at day [D]1 + oxaliplatin, 100 mg/m² at D2, arm A) or GEMOX + cetuximab (500 mg/m² at D1 or 2, arm B), every 2 weeks. The primary endpoint was crude 4-month progression-free survival (PFS) rate (H0, <40%; H1, ≥60%; planned sample size, 100 pts, increased to 150 pts by amendment to allow subgroup analyses). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), PFS, overall survival (OS), and toxicity (NCI-CTC v3.0). Exploratory endpoints included early metabolic response as assessed by PET at 1 month, and tumor KRAS mutational analysis. Results: From Oct. 2007 to Dec. 2009, we enrolled 150 pts (median age, 62 years; male, 57%; metastatic, 79%; cholangiocarcinoma, 84%; median follow-up, 30 months) (Table). Conclusions: GEMOX-cetuximab regimen was well tolerated and met its primary endpoint (4-month PFS ≥60%). However, median PFS and OS were similar in both arms. Exploratory analyses (e.g., KRAS tumor status) are underway to identify pt subgroups deriving benefit from the addition of cetuximab to CTx. [Table: see text]

Randomized phase II study of pharmacodynamic separation (PDS) of pemetrexed (Pem) and erlotinib (Erl) versus pem alone in patients (pts) with advanced non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8097-8097 ◽  
Author(s):  
Tianhong Li ◽  
Bilal Piperdi ◽  
William Vincent Walsh ◽  
Mimi Kim ◽  
Rasim Gucalp ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Performance Status ◽  
Progression Free Survival ◽  
Dose Schedule ◽  
Phase Iii ◽  
Smoking History ◽  
Clinical Activity ◽  
P Value ◽  
Randomized Phase Ii

8097 Background: Preclinical and phase I studies showed that PDS optimizes cytotoxicity of concurrent EGFR inhibitors and chemotherapy. We conducted a randomized phase II trial to assess relative efficacy of Pem alone (Arm A) versus Pem +Erl on a PDS dose-schedule (Arm B) as 2nd-line therapy in pts with advanced NSCLC (NCT00950365). Methods: Eligible pts were randomized 2:1 (Arm B: A), stratified by sex, smoking history, and performance status (0/1 vs 2). Accrual was restricted to non-squamous histology in 2009. Treatment: Arm A – Pem 500 mg/m2IV on day 1; Arm B – Pem + Erl 150 mg po QD on days 2-17. 1 cycle = 3 weeks. Primary endpoint was progression-free survival (PFS). 50 pts in Arm B were needed to detect an increase in median PFS from ~3 to 4.5 months. Results: 83 pts were entered. Age: 63 yo. Female: 42 (53%). Smoking ≥15PY: 58 (72%). Nonsquamous: 78 (99%). The primary endpoint of the study was met: Efficacy results from 79 eligible pts showed 1.6-fold longer PFS in Arm B (4.6 m) compared to Arm A (2.8 m). Although the study was not designed to directly compare two arms, p value was 0.052. Toxicity: G3/4 Hem (A/B): 8(30%)/12(23%); Neutropenia with infection (A/B): 0/3(6%). G3/4 Non-Hem (A/B): skin rash: 0/3(6%); diarrhea: 0/2(4%); joint pain: 1(4%)/6(11.5%). Treatment related death (A/B): 0/1. Interstitial lung disease (A/B): 0/1. Conclusions: PDS of Pem and Erl is well tolerated and has promising clinical activity in 2nd-line non-squamous NSCLC. Ongoing correlative studies aim to identify a subgroup of patients who might benefit most from this treatment, which will guide the design of a confirmatory phase III study. (UL1 RR024146, P30CA093373, Lilly, Astellas) Clinical trial information: NCT00950365. [Table: see text]

Phase II study of alternate-day oral therapy with S-1 for unresectable advanced pancreatic cancer: An updated report.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 252-252
Author(s):  
Sohei Satoi ◽  
Motoki Miyazawa ◽  
Masaji Tani ◽  
Manabu Kawai ◽  
Seiko Hirono ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Effects ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Current Data ◽  
Standard Regimen ◽  
Grade 3

252 Background: Based on the results of GEST, S-1 was confirmed to be non-inferior to gemcitabine. However, the recommended regimen of 4 weeks of administration interrupted by 2 weeks of drug withdrawal frequently causes adverse effect. Grade3/4 toxicities (%) in S-1 were neutropenia 8.8, anorexia 11.4, diarrhea 5.5. On the other hand, we experienced in clinical practice that the alternate-day administration of S-1 reduced adverse effects and was tolerable for unresectable advanced pancreatic cancer patients unwilling to continue the standard daily administration. We therefore conducted a multi-center cooperative prospective study to compare daily with alternate-day administration of S-1 for unresectable advanced pancreatic cancer. Methods: Patients with unresectable advanced pancreatic cancer (PS, 0 to 1; age, 20 to 80 years; no other therapy) were eligible for enrollment in this trial. S-1 was administered a dose of 40 to 60 mg twice daily, assigned according to body-surface area, on Monday, Wednesday, Friday, and Sunday (specified days). Each treatment cycle will be 42 days (6 weeks). The primary endpoint was overall survival (OS). Secondary endpoints were safety, response rate (RR), progression free survival (PFS), time to treatment failure (TTF). Results: A total of 50 patients were enrolled from Sep 2009 to Feb 2011. 48 patients were evaluable for response. Male/Female was 21/27, PS: 0/1 was 40/8. With a median follow-up time of 28.2 months, OS as primary endpoint was 8.4 months (95% CI, 5.4-10.8) with the 1 year survival rate 29.2%. PFS was 5.5 months, and TTF was 3.9 months. RR was 10.4% (95% CI: 3.5-19.1), and Disease Control rate was 79.2%. Grade 3/4 hematological and non-hematological toxicities were minor. All of those adverse reactions were tolerable and reversible. Conclusions: We will report the data from the final analysis at this meeting. The current data show mitigation of adverse effects with alternate-day administration of S-1, and it appears to be a more sustainable option for unresectable advanced pancreatic cancer. A randomized phase II trial comparing this regimen of S-1 with standard regimen of S-1 is ongoing. Clinical trial information: 000003453.

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.

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]

A phase II trial of oxaliplatin and docetaxel in patients with androgen independent prostate cancer (AIPC) who have progressed to two prior regimens of chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15545-15545 ◽  
Author(s):  
T. Feinstein ◽  
L. J. Appleman ◽  
D. M. Friedland ◽  
S. A. Jacobs ◽  
W. A. Ferri ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Free Survival ◽  
Duration Of Response ◽  
Psa Response ◽  
Previously Treated ◽  
Grade 3

15545 Background: Single agent docetaxel has demonstrated survival benefit in AIPC. In a phase I study of single agent oxaliplatin at our institution, two patients with AIPC experienced a substantial and durable reduction in PSA. Thus, we hypothesised that a combination of oxaliplatin and docetaxel maybe beneficial in AIPC. Methods: This single arm phase II trial in patients with previously treated (0–2 regimens) and progressive AIPC commenced in June 2005, with the objectives of evaluating PSA response rates, progression free survival, and the toxicity (tolerance/safety) of the regimen. In patients with soft tissue disease, measurable responses were assessed by RECIST criteria. Using Simon stage II design, a total of 37 patients with AIPC will be accrued. No prior treatment with platinum was allowed. Treatment consisted of oxaliplatin (110 mg/m2) and docetaxel (60 mg/m2), administered intravenously every 21 days for a maximum of 6 cycles. Results: 27 men have been enrolled to date: median age 66 yrs (56–84). 21 of 27 men have completed at least two cycles of the above regimen, and are evaluable. Prior therapies included antiandrogens (100%); ketaconazole (14%); docetaxel alone or in combination (27%); anthracyclines (27%); and vaccine (5%). Median PSA at baseline was 88 ng/ml (range 2.2–3559.4). 62% of patients received all six cycles. PSA declines of ≥50% were noted in 11 of 21 patients: 3 of 8 responders being chemo-naïve; and 8 of 13 with prior chemotherapy exposure. In addition, 4 of 11 patients with measurable disease at baseline, had a partial response. Treatment was well tolerated with no treatment-related deaths. The most significant grade 3/4 adverse event (AE) was neutropenia (43%). Grade 2 or less fatigue (66%), neuropathy (53%) diarrhea (47%), nausea (41%), anorexia (29%), thrombocytopenia (12%) and anemia (6%). Conclusions: The combination of oxaliplatin and docetaxel has promising activity in both chemo-naïve and previously treated AIPC. This 2-stage study will accrue a total of 37 patients. Final analysis will include time to progression, duration of response, and median survival. [Table: see text]

Phase I randomized phase II trial of gemcitabine, erlotinib, and cixutumumab versus gemcitabine plus erlotinib as first-line treatment in patients with metastatic pancreatic cancer (SWOG-0727).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 198-198 ◽  
Author(s):  
Philip Agop Philip ◽  
Bryan H. Goldman ◽  
Ramesh K. Ramanathan ◽  
Heinz-Josef Lenz ◽  
Andrew M. Lowy ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase I ◽  
Phase Ii ◽  
Complex Disease ◽  
Performance Status ◽  
Fasting Blood Glucose ◽  
Progression Free Survival ◽  
Sensitivity Analyses ◽  
Randomized Phase Ii ◽  
Grade 3

198 Background: Targeting a single pathway in pancreatic adenocarcinoma (PAC) did not impact the natural history of this molecularly complex disease. Epidermal growth factor receptor (EGFR) targeting with erlotinib marginally improved the outcome of patients with advanced disease. We tested the hypothesis that if the EGFR and IGF-1R pathways are simultaneously blocked then progression free survival (PFS) would be significantly improved by abrogating reciprocal signaling. Methods: S0727 was a phase I/randomized phase II (RP2) study testing the anti-IGF-1R monoclonal antibody cixutumumab combined with erlotinib and gemcitabine in patients with metastatic PAC. The control arm was erlotinib plus gemcitabine. The primary endpoint of the RP2 portion of the study was PFS. Eligibility included patients with untreated metastatic disease, performance status 0/1, fasting blood glucose less than institutional upper limit of normal, and willingness to provide tissue and blood specimens for correlative studies. Results: In Phase I portion (n=10) safety of cixutumumab 6 mg/kg IV/wk, erlotinib 100 mg/day orally and gemcitabine 1000 mg/m2 IV D 1,8, and 15 of a 28-day cycle was established. In the RP2 portion (n=124) 114 eligible patients (median age 63) were included. On the cixutumumab arm, 59% of patients were female vs. 41% on control arm. Median PFS and overall survival were 4 and 7 months, respectively, in both arms. Four patients on cixutumumab remain on treatment; sensitivity analyses show no impact on the conclusions. Major grade 3 and 4 toxicities were (cixutumumab/control) elevation of transaminases (12%/6%), fatigue (24%/21%), gastrointestinal (35%/28%), and hematologic (53%/39%). Grade 3/4 hyperglycemia was seen in 27% of patients on cixutumumab. Grade 3 or 4 kin toxicity was similar in both arms of the study (< 5%). Five treatment-related deaths were reported: 2 cardiac on each arm, 1 pulmonary on cixutumumab. Conclusions: IGF-1R inhibitor cixutumumab did not improve the progression free or overall survival in patients with metastatic PAC treated with erlotinib and gemcitabine in a molecularly unselected population.

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