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

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2

Conditions: Pancreatic Cancer

Treatments: Drug: gemcitabine hydrochloride; Biological: panitumumab; Drug: capecitabine; Drug: fluorouracil; Radiation: radiation therapy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00601627

NCI-2009-01088 (Registry Identifier)

CDR0000584104 (Registry Identifier)

NCCTG-N064A

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 52 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

• 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

PRIOR CONCURRENT THERAPY:

• 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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52 participants in 1 patient group

Panitumumab

Experimental group

Description:

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 completion of radiation therapy: Gemcitabine on days 1, 8, and 15 of each cycle, for 3 cycles; Panitumumab on days 1 and 15 of each cycle, for 3 cycles. Maintenance therapy: Panitumumab on days 1 and 15 of each cycle, for 6 cycles.

Treatment:

Drug: capecitabine

Drug: gemcitabine hydrochloride

Radiation: radiation therapy

Drug: fluorouracil

Biological: panitumumab