Erlotinib and Gemcitabine With or Without Panitumumab in Treating Patients With Metastatic Pancreatic Cancer - Full Text View

Sponsors and Collaborators:	North Central Cancer Treatment Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00550836

Purpose

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.

Condition	Intervention	Phase
Pancreatic Cancer	Drug: erlotinib hydrochloride Drug: gemcitabine hydrochloride Drug: panitumumab	Phase II

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Gemcitabine hydrochloride Gemcitabine Erlotinib Erlotinib hydrochloride Pancrelipase Ultrase Panitumumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	Randomized Phase II Trial of Panitumumab, Erlotinib and Gemcitabine vs. Erlotinib and Gemcitabine in Patients With Untreated, Metastatic Pancreatic Adenocarcinoma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Confirmed response rate [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Time to treatment failure [ Designated as safety issue: No ]
Adverse events [ Designated as safety issue: Yes ]

Estimated Enrollment:	98
Study Start Date:	November 2007
Estimated Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Active Comparator Patients receive gemcitabine hydrochloride and oral erlotinib hydrochloride. 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.	Drug: erlotinib hydrochloride Given orally Drug: gemcitabine hydrochloride Given IV
Arm II: Experimental Patients receive gemcitabine hydrochloride, erlotinib hydrochloride, and panitumumab. 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.	Drug: erlotinib hydrochloride Given orally Drug: gemcitabine hydrochloride Given IV Drug: panitumumab Given IV

Arms

Assigned Interventions

Arm I: Active Comparator

Patients receive gemcitabine hydrochloride and oral erlotinib hydrochloride. 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.

Drug: erlotinib hydrochloride

Given orally

Drug: gemcitabine hydrochloride

Given IV

Arm II: Experimental

Patients receive gemcitabine hydrochloride, erlotinib hydrochloride, and panitumumab. 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.

Drug: erlotinib hydrochloride

Given orally

Drug: gemcitabine hydrochloride

Given IV

Drug: panitumumab

Given IV

Detailed 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, 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.

After the second progression, patients are followed every 3-6 months for 2 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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
Hemoglobin ≥ 9.0 g/dL
Total bilirubin normal (patients may be stented)
AST/ALT ≤ 2.5 x upper limit of normal (ULN)
Creatinine ≤ 2.0 x 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 history of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis, or any evidence of interstitial lung disease) on baseline chest x-ray or chest CT scan
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 enteral hyperalimentation

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
More than 4 weeks since prior and no concurrent or planned participation in another experimental drug study except studies with specific interventions intended to treat rashes associated with EGFR agents (e.g., N05C4)
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 chronic immunosuppressive agents (e.g., methotrexate, cyclosporine, or corticosteroids)
No concurrent immunotherapy or radiotherapy
No other concurrent chemotherapy
No concurrent colony-stimulating factors during the first course of study therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00550836

Sponsors and Collaborators

North Central Cancer Treatment Group

National Cancer Institute (NCI)

Investigators

Study Chair:	George P. Kim, MD	Mayo Clinic
Investigator:	Muhammad Salim, MD	Saskatchewan Cancer Agency

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000571863, NCCTG-N064B
Study First Received:	October 26, 2007
Last Updated:	December 20, 2008
ClinicalTrials.gov Identifier:	NCT00550836
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the pancreas
duct cell adenocarcinoma of the pancreas
stage IV pancreatic cancer

Study placed in the following topic categories:

Erlotinib
Digestive System Neoplasms
Pancreatic Neoplasms
Endocrine System Diseases
Pancrelipase
Carcinoma
Digestive System Diseases

Gastrointestinal Neoplasms
Pancreatic Diseases
Endocrinopathy
Adenocarcinoma
Gemcitabine
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors

Protein Kinase Inhibitors
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on January 15, 2009