Panitumumab, Chemotherapy, And External-Beam Radiation Therapy In Treating Patients With Locally Advanced Pancreatic Cancer That Cannot Be Removed By Surgery

Study Overview

Panitumumab, Chemotherapy, and External-Beam Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer That Cannot be Removed by Surgery

RATIONALE: 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. Drugs used in chemotherapy, such as fluorouracil, capecitabine, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. External-beam radiation therapy uses high-energy x-rays to kill tumor cells. Panitumumab may also stop the growth of pancreatic cancer by blocking blood flow to the tumor and make tumor cells more sensitive to radiation therapy. Giving panitumumab together with chemotherapy and radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving panitumumab together with chemotherapy and external-beam radiation therapy works in treating patients with locally advanced pancreatic cancer that cannot be removed by surgery.

OBJECTIVES: Primary * To evaluate the 1-year survival rate in patients with locally advanced pancreatic cancer treated with panitumumab and continuous infusion fluorouracil administered concurrently with external-beam radiotherapy followed by gemcitabine and panitumumab. Secondary * To determine overall survival, time to disease progression, confirmed response rate, duration of response, and time to treatment failure in patients treated with this regimen. * To determine adverse events in patients treated with this regimen. OUTLINE: * Panitumumab and chemoradiotherapy : Patients undergo external-beam radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-38. Patients also receive panitumumab IV over 1 hour on days 1, 15, and 29 and fluorouracil IV continuously over 24 hours daily OR oral capecitabine twice daily beginning on day 1 and continuing through the last day of radiotherapy. * Panitumumab and chemotherapy: Beginning 4-6 weeks after completion of panitumumab and chemoradiotherapy, patients receive panitumumab IV over 1 hour on days 1 and 15 and gemcitabine IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 3 courses. Patients then proceed to maintenance therapy. * Maintenance therapy: Patients receive panitumumab IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year.

Pancreatic Cancer

BIOLOGICAL: panitumumab
DRUG: capecitabine
DRUG: fluorouracil
DRUG: gemcitabine hydrochloride
RADIATION: radiation therapy

NCCTG-N064A
NCI-2009-01088 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trials Reporting System))
CDR0000584104 (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 2008-01-18	Results First Submitted 2017-02-21	Last Update Submitted that met QC Criteria 2017-02-21
First Submitted that Met QC Criteria 2008-01-24	Results First Submitted that Met QC Criteria 2017-02-21	Last Update Posted (ACTUAL) 2017-04-05
First Posted (ACTUAL) 2008-01-28	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:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Panitumumab Chemotherapy concurrent with radiation: Radiation 5 days per week for 5½ weeks; Panitumumab on days 1, 15, and 29 of radiation therapy 5-fluorouracil (5FU) continuous infusion, starting on day 1 and through last day of radiation. 4-6 weeks after completi	BIOLOGICAL: panitumumab DRUG: capecitabine DRUG: fluorouracil DRUG: gemcitabine hydrochloride RADIATION: radiation therapy

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Panitumumab

Chemotherapy concurrent with radiation: Radiation 5 days per week for 5½ weeks; Panitumumab on days 1, 15, and 29 of radiation therapy 5-fluorouracil (5FU) continuous infusion, starting on day 1 and through last day of radiation. 4-6 weeks after completi

BIOLOGICAL: panitumumab

DRUG: capecitabine

DRUG: fluorouracil

DRUG: gemcitabine hydrochloride

RADIATION: radiation therapy

Primary Outcome Measures	Measure Description	Time Frame
One Year Survival Rate	The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the exact binomial method.	Baseline to 12 months

Secondary Outcome Measures	Measure Description	Time Frame
Overall Survival	Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier	baseline to 2 years
Progression Free Survival (PFS)	Progression Free Survival is defined as the time from registration to the earliest documented evidence of disease progression.	baseline to 2 years
Confirmed Response Rate	A confirmed tumor response is defined to be a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluations at least 4 weeks apart according to the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. A complete response is defined as the disappearance of all target and non-target lesions. A partial response is defined as at least a 30% decrease in the sum of the longest diameter (LD) of the target lesion from baseline. Confirmed tumor response will be evaluated using the first 6 cycles of treatment.	baseline to 2 years
Duration of Response	Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented.	baseline to 2 years
Time to Treatment Failure	Time to treatment failure is defined to be the time from the date of registration to the date at which the patient is removed from treatment due to progression, adverse events, or refusal. The distribution of survival time will be estimated using the method of Kaplan-Meier.	baseline 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 unresectable adenocarcinoma of the pancreas

Including subtotal resection and gross residual disease

No microscopic residual disease only
Measurable disease is not required
Disease is encompassable within standard radiotherapy fields for pancreatic cancer
No evidence of metastatic disease outside of the planned radiotherapy field
No cystadenocarcinoma of the pancreas or pancreatic tumors of neuroendocrine origin
No distant metastases (i.e., liver or lung metastases or peritoneal spread)
No history or known presence of CNS metastases

Eastern Cooperative Oncology Group (ECOG) performance status 0-1
ANC ≥ 1,500/mm³
Hemoglobin ≥ 9.0 g/dL
Platelet count ≥ 100,000/mm³
Total bilirubin ≤ 3 times upper limit of normal (ULN)
NOTE: *Biliary stent placement or surgical bypass should be considered prior to treatment if impending bile duct obstruction by tumor
AST ≤ 3 times ULN
Creatinine ≤ 2.0 times ULN
Magnesium normal
Willing to return to an North Central Cancer Treatment Group (NCCTG) institution for follow-up
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for at least 6 months after treatment with panitumumab
No prior or concurrent malignancy unless disease-free ≥ 3 years except for non-melanoma skin cancer, carcinoma in situ of the cervix, or organ confined prostate cancer with Gleason score < 7
No nausea or vomiting > grade 1
No uncontrolled intercurrent illness including, but not limited to, any the following:

Ongoing or active infection
Psychiatric illness or social situations that would limit compliance with study requirements
No New York Heart Association clinically significant cardiovascular disease ≥ grade 2, including any of the following within the past year:

Myocardial infarction
Unstable angina
Symptomatic congestive heart failure
Serious, uncontrolled cardiac arrhythmia
No known HIV positivity
No known hepatitis C virus or acute or chronic active hepatitis B infection
Adequate oral nutrition

More than 21 days since prior laparotomy
No prior anti-epidermal growth factor receptor (EGFR) antibody therapy (e.g., cetuximab)
No prior small molecule EGFR inhibitors (e.g., gefitinib, erlotinib, or lapatinib)
No prior radiotherapy that would overlap with planned radiotherapy fields
No prior or other concurrent chemotherapy
No prior or other concurrent biologic therapy
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 concurrent enteral hyperalimentation
No concurrent chronic immunosuppressive agents (e.g., methotrexate, cyclosporine, or corticosteroids)
No concurrent colony-stimulating factors during the first course of therapy
No other concurrent immunotherapy or radiotherapy

Collaborators and Investigators

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

National Cancer Institute (NCI)

Investigators

STUDY_CHAIR: George 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, Haddock MG, Dakhil SR, Behrens RJ, Alberts SR. N064A (Alliance): Phase II Study of Panitumumab, Chemotherapy, and External Beam Radiation in Patients with Locally Advanced Pancreatic Adenocarcinoma. Oncologist. 2022 Jul 5;27(7):534-e546. doi: 10.1093/oncolo/oyac002.

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