Erlotinib and Gemcitabine With or Without Panitumumab in Treating Patients With Metastatic Pancreatic Cancer

Brief summary public domain (ClinicalTrials.gov)

RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Panitumumab may also stop the growth of pancreatic cancer by blocking blood flow to the tumor. PURPOSE: This randomized phase II trial is studying how well giving panitumumab together with gemcitabine and erlotinib works compared to giving gemcitabine and erlotinib alone in treating patients with metastatic pancreatic cancer.

Detailed description public domain (ClinicalTrials.gov)

OBJECTIVES: Primary * To assess whether the addition of panitumumab (a dual-epidermal growth factor receptor inhibitor) to standard chemotherapy comprising gemcitabine hydrochloride and erlotinib hydrochloride results in an improvement in overall survival of patients with previously untreated, metastatic adenocarcinoma of the pancreas. Secondary * To compare objective response rates, progression-free survival, time to treatment failure, quality of life, and adverse event rates in patients treated with these regimens. * To evaluate the downstream marker, KRAS, in stool specimens. OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance status (0 vs 1) and prior adjuvant chemotherapy (yes vs no). The first 6 patients are assigned to arm II. Subsequent patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days for 2 courses. Patients achieving a complete response (CR) after 2 courses receive 2 additional courses of treatment; patients achieving a partial response (PR) receive retreatment as above in the absence of disease progression or unacceptable toxicity. Patients achieving a CR after 4 courses of treatment receive maintenance therapy comprising erlotinib hydrochloride daily until the first disease progression. After the first progression, patients are retreated with gemcitabine hydrochloride and erlotinib hydrochloride until second progression (using the first progression tumor measurements as the new baseline reference). * Arm II: Patients receive gemcitabine hydrochloride and erlotinib hydrochloride as in arm I and panitumumab IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for 2 courses. Patients achieving a CR after 2 courses receive 2 additional courses of treatment; patients achieving a PR receive retreatment as above in the absence of disease progression or unacceptable toxicity. Patients achieving a CR after 4 courses of treatment receive maintenance therapy comprising erlotinib hydrochloride daily and panitumumab every 2 weeks until the first disease progression. After the first progression, patients are retreated with gemcitabine hydrochloride, erlotinib hydrochloride, and panitumumab until second progression (using the first progression tumor measurements as the new baseline reference). Stool samples are collected at baseline and analyzed for KRAS mutations via protein analyses. Quality of life will be assessed at baseline, every 2 courses during treatment, and at the end of treatment. After the second progression, patients are followed every 3-6 months for 2 years.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Overall Survival [Up to 2 years]. Median, months (95% Confidence Interval). Arm A: GE (n=46): 4.2 (3.5 to 7.8); Arm B: PGE (n=46): 8.3 (4.5 to 10). Analysis, Arm A: GE vs Arm B: PGE: p=0.36; Log Rank; superiority.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Confirmed Response Rate [Up to 2 years]. Number, rate of confirmed response (95% Confidence Interval). Arm A: GE (n=46): 0.087 (0.024 to 0.208); Arm B: PGE (n=46): 0.065 (0.014 to 0.179). Analysis, Arm A: GE vs Arm B: PGE: p=1.0; Fisher Exact; other.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Progression-free Survival [Up to 2 years]. Median, months (95% Confidence Interval). Arm A: GE (n=46): 2.0 (1.8 to 3.3); Arm B: PGE (n=46): 3.6 (2.3 to 4.5). Analysis, Arm A: GE vs Arm B: PGE: p=0.419; Log Rank; superiority.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Time to Treatment Failure [Up to 2 years]. Median, months (95% Confidence Interval). Arm A: GE (n=46): 2.0 (1.8 to 2.5); Arm B: PGE (n=46): 3.8 (2.0 to 4.2). Analysis, Arm A: GE vs Arm B: PGE: p=0.36; Log Rank; other.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Frequency and Severity of Observed Adverse Effects [Up to 2 years]. Number, participants. Grade 3+ Adverse Event: Arm A: GE (n=46): 41; Arm B: PGE (n=46): 41. Grade 4+ Adverse Event: Arm A: GE (n=46): 15; Arm B: PGE (n=46): 14.