Erlotinib And Gemcitabine With Or Without Panitumumab In Treating Patients With Metastatic Pancreatic Cancer

Study Overview

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

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.

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.

Pancreatic Cancer

BIOLOGICAL: panitumumab
DRUG: erlotinib hydrochloride
DRUG: gemcitabine hydrochloride

NCCTG-N064B
NCI-2009-01089 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trials Reporting System))
CDR0000571863 (REGISTRY Identifier) (REGISTRY: PDQ (Physician Data Query))

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2007-10-26	Results First Submitted 2017-02-21	Last Update Submitted that met QC Criteria 2017-02-21
First Submitted that Met QC Criteria 2007-10-26	Results First Submitted that Met QC Criteria 2017-02-21	Last Update Posted (ACTUAL) 2017-04-05
First Posted (ACTUAL) 2007-10-30	Results First Posted 2017-04-05	Last Verified 2017-02

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
ACTIVE_COMPARATOR: Arm A: GE 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 addi	DRUG: erlotinib hydrochloride Given orally DRUG: gemcitabine hydrochloride Given IV
EXPERIMENTAL: Arm B: PGE 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	BIOLOGICAL: panitumumab Given IV DRUG: erlotinib hydrochloride Given orally DRUG: gemcitabine hydrochloride Given IV

Participant Group/Arm

Intervention/Treatment

ACTIVE_COMPARATOR: Arm A: GE

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 addi

DRUG: erlotinib hydrochloride

Given orally

DRUG: gemcitabine hydrochloride

Given IV

EXPERIMENTAL: Arm B: PGE

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

BIOLOGICAL: panitumumab

Given IV

DRUG: erlotinib hydrochloride

Given orally

DRUG: gemcitabine hydrochloride

Given IV

Primary Outcome Measures	Measure Description	Time Frame
Overall Survival	Overall Survival is defined as the time from registration to death due to any cause. The estimate will be done using the Kaplan-Meier method. The primary goal of this trial is to compare the experimental arm (Arm B) to the standard arm (Arm A). The primary analysis will be a comparison of Arm A to Arm B using a one-sided log-rank test between the 2 Kaplan-Meier curves.	Up to 2 years

Secondary Outcome Measures	Measure Description	Time Frame
Confirmed Response Rate	Evaluated using RECIST version 1.0. Confirmed tumor response rate was defined as achieving partial response (PR) or complete response (CR) in two consecutive assessments at least 6 weeks apart. CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. The confirmed response rate is reported as the number of participants with confirmed responses divided by the number of evaluated participants.	Up to 2 years
Progression-free Survival	Progression-free survival is defined as the time from randomization to documentation of disease progression or death, whichever comes first. Progression is defined as at least a 20% increase in the sum of longest dimension (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. The progression-free survival curves will be compared between the 2 arms using a log-rank test.	Up to 2 years
Time to Treatment Failure	Time to treatment failure is defined to be the time from the date of randomization to the date at which the patient is removed from treatment due to progression, adverse events, or refusal. If the patient is considered to be a major treatment violation or is taken off study as a nonprotocol failure, the patient will be censored on the date they are removed from treatment. The time to treatment failure will be estimated using the method of Kaplan-Meier.	Up to 2 years
Frequency and Severity of Observed Adverse Effects	Patients are assessed for Adverse events each cycle using the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0). The maximum grade for each type of adverse event will be recorded for each patient, and tables will be reviewed to determine adverse event patterns. The number of patients in each arm that reported a grade 3 or higher adverse event and a grade 4 or higher adverse event are reported. A complete listing of all adverse events is reported in the Adverse Events section.	Up to 2 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

STUDY_CHAIR: George P. Kim, MD, Mayo Clinic

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Halfdanarson TR, Foster NR, Kim GP, Meyers JP, Smyrk TC, McCullough AE, Ames MM, Jaffe JP, Alberts SR. A Phase II Randomized Trial of Panitumumab, Erlotinib, and Gemcitabine Versus Erlotinib and Gemcitabine in Patients with Untreated, Metastatic Pancreatic Adenocarcinoma: North Central Cancer Treatment Group Trial N064B (Alliance). Oncologist. 2019 May;24(5):589-e160. doi: 10.1634/theoncologist.2018-0878. Epub 2019 Jan 24.

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