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

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2

Conditions: Pancreatic Cancer

Treatments: Drug: gemcitabine hydrochloride; Biological: panitumumab; Drug: erlotinib hydrochloride

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00550836

NCI-2009-01089 (Registry Identifier)

NCCTG-N064B

CDR0000571863 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 104 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas (ductal or undifferentiated)

  • Metastatic disease

• No islet cell, acinar cell, or cystadenocarcinomas

• No locally advanced disease

• No history or known presence of CNS metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Life expectancy ≥ 3 months
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Total bilirubin ≤ 2 times upper limit of normal (ULN) (patients may be stented)
• AST ≤ 2.5 times ULN
• Creatinine ≤ 2.0 times ULN
• Magnesium ≥ lower limit of normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Willing to provide a stool specimen
• No malignancy diagnosed within the past 3 years except basal cell or squamous cell skin cancer, prostate cancer (Gleason < 7), or carcinoma in situ of the cervix
• No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
• No clinically significant cardiovascular disease (i.e., myocardial infarction, unstable angina, symptomatic congestive heart failure, or serious uncontrolled cardiac arrhythmia) within the past year
• No known positive test(s) for HIV infection, hepatitis C virus, or acute or chronic active hepatitis B infection
• No liver dysfunction from cirrhosis or viral hepatitis
• No enteral hyperalimentation
• No grapefruit or grapefruit juice during the study

PRIOR CONCURRENT THERAPY:

• Recovered from prior therapy

• More than 4 months since prior radiotherapy, immunotherapy, or biologic therapy

• More than 4 weeks since prior and no elective or planned major surgery

• More than 2 weeks since prior minor and no elective or planned surgery

• No prior cytotoxic chemotherapy for metastatic disease

  • Adjuvant chemotherapy for completely resected disease or chemoradiotherapy for locally advanced disease is allowed, provided it was administered > 6 months prior to study entry

    • Adjuvant chemotherapy must not have contained an EGFR inhibitor

  • Gemcitabine hydrochloride used as either a radiosensitizer or as maintenance therapy is allowed, provided more than 6 months have elapsed since the last day of treatment

• No prior anti-EGFR antibody therapy (e.g., cetuximab) or treatment with small molecule EGFR inhibitors (e.g., gefitinib hydrochloride, erlotinib hydrochloride, or lapatinib)

• No concurrent immunotherapy or radiotherapy

• No other concurrent chemotherapy

• No concurrent colony-stimulating factors during the first course of study therapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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104 participants in 2 patient groups

Arm A: GE

Active Comparator group

Description:

Patients receive 1000 mg/m^2 gemcitabine hydrochloride IV on days 1, 8, and 15; and 100 mg oral erlotinib hydrochloride 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. Patients achieving a CR after 4 courses of treatment receive erlotinib hydrochloride until the first disease progression. After the first progression, patients are retreated with gemcitabine hydrochloride and erlotinib hydrochloride until second progression.

Treatment:

Drug: erlotinib hydrochloride

Drug: gemcitabine hydrochloride

Arm B: PGE

Experimental group

Description:

Patients receive 1000 mg/m^2 gemcitabine hydrochloride IV on days 1, 8, and 15; 100 mg oral erlotinib hydrochloride on days 1 - 28; and 4.0 mg/kg panitumumab IV 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. Patients achieving a CR after 4 courses of treatment receive erlotinib hydrochloride and panitumumab until the first disease progression. After the first progression, patients are retreated with gemcitabine hydrochloride, erlotinib hydrochloride, and panitumumab until second progression.

Treatment:

Drug: erlotinib hydrochloride

Biological: panitumumab

Drug: gemcitabine hydrochloride