Bevacizumab or Cetuximab And Gemcitabine Hydrochloride, Capecitabine, and Radiation Therapy in Treating Patients With Pacreatic Cancer That Has Been Completely Removed By Surgery

NCT00305877 | Completed Phase 2 Results

• 7 other identifiers: NCI-2012-02969CALGB-ECOG-E2204SWOG-ECOG-E2204ECOG-E2204NCCTG-ECOG-E2204E2204U10CA021115
• Study Type: interventional
• Target: 137
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized phase II trial is studying bevacizumab to see how well it works compared to cetuximab when given together with gemcitabine, capecitabine, and radiation therapy in treating patients with pancreatic cancer that has been completely removed by surgery. Monoclonal antibodies, such as bevacizumab and cetuximab, 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. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Cetuximab may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bevacizumab or cetuximab together with gemcitabine, capecitabine, and radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether bevacizumab is more effective than cetuximab when given together with gemcitabine, capecitabine, and radiation therapy in treating pancreatic cancer.

Conditions

Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients With Specific Protocol Defined Adverse Event at Conclusion of All Therapy

  Specific toxicities to be monitored pursuant to the primary endpoint include: 1. Any grade 5 toxicities 2. Grade 4 dyspnea, neutropenic fever, allergic reaction, rash, wound dehiscence, wound infection, hypertension 3. Grade 3 or higher arterial thromboembolic phenomena, bleeding, phlebitis/deep vein thrombosis (DVT)/pulmonary embolism (PE), hemorrhage, ileus, bowel perforation, diarrhea, and mucositis 4. ECOG performance status decline by 2 or greater for \>24 hours 5. Weight loss \>10%

  Every 2 weeks while on treatment and for 30 days after the end of treatment

Secondary Outcomes (2)

• Two-year Overall Survival Rate

  Assessed every 3 months for 2 years

• Two-year Disease-free Survival (DFS)

  Assessed every 3 months for 2 years, and every 6 months after completion of treatment for 2 years, then annually for 3 years

Study Arms (2)

Arm I (cetuximab, gemcitabine, capecitabine, radiation)

EXPERIMENTAL

Patients receive cetuximab IV over 60-120 minutes on day 1, once weekly, in weeks 1-24; gemcitabine hydrochloride IV over 30 minutes on day 1, once weekly, in weeks 1-3, 13-15, 17-19, and 21-23; oral capecitabine twice daily on days 1-5, 5 days a week, in weeks 5-10. Patients also undergo radiotherapy once daily, 5 days a week, beginning in week 5 and continuing for approximately 5½ weeks (25 fractions).

Biological: cetuximab; Drug: gemcitabine hydrochloride; Drug: capecitabine; Radiation: radiation therapy; Other: laboratory biomarker analysis

Arm II (bevacizumab, gemcitabine, capecitabine, radiation)

EXPERIMENTAL

Patients receive bevacizumab IV over 60-90 minutes on day 1 in weeks 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, and 23. Patients also receive gemcitabine hydrochloride and capecitabine and undergo radiotherapy as in arm I.

Drug: gemcitabine hydrochloride; Drug: capecitabine; Radiation: radiation therapy; Biological: bevacizumab; Other: laboratory biomarker analysis

Interventions

cetuximab BIOLOGICAL

Given IV

Also known as: C225, C225 monoclonal antibody, IMC-C225, MOAB C225, monoclonal antibody C225

Arm I (cetuximab, gemcitabine, capecitabine, radiation)

gemcitabine hydrochloride DRUG

Given IV

Also known as: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar

Arm I (cetuximab, gemcitabine, capecitabine, radiation); Arm II (bevacizumab, gemcitabine, capecitabine, radiation)

capecitabine DRUG

Given orally

Also known as: CAPE, Ro 09-1978/000, Xeloda

Arm I (cetuximab, gemcitabine, capecitabine, radiation); Arm II (bevacizumab, gemcitabine, capecitabine, radiation)

radiation therapy RADIATION

Undergo radiation therapy

Also known as: irradiation, radiotherapy, therapy, radiation

Arm I (cetuximab, gemcitabine, capecitabine, radiation); Arm II (bevacizumab, gemcitabine, capecitabine, radiation)

bevacizumab BIOLOGICAL

Given IV

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

Arm II (bevacizumab, gemcitabine, capecitabine, radiation)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (cetuximab, gemcitabine, capecitabine, radiation); Arm II (bevacizumab, gemcitabine, capecitabine, radiation)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed evidence of pancreatic carcinoma
• Patients must have had all gross disease resected (R0 or R1 resection)
• Patients undergoing an R2 resection are not eligible
• Patients must have had no prior chemotherapy or radiation therapy for pancreatic cancer and must have had no prior EGFR/VEGF inhibition
• Patient must have ECOG performance status of 0-2
• Leukocytes \>= 3,000/μL
• ANC \>= 1,500/μL
• Platelets \>= 100,000/μL
• Total bilirubin Within normal institutional limits
• AST (SGOT)/ALT(SGPT) =\< 2.5 X institutional upper limit of normal
• Creatinine clearance \>= 60 mL/min for patients with creatinine levels above institutional normal
• Patients must be \> 4 weeks and =\< 8 weeks post-surgery at time of study registration (may be up to 10 weeks post-surgery prior to start of study therapy)
• Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception prior to study entry
• Women must not be pregnant or breast-feeding; all agents used in this study as well as radiation therapy to the abdomen have the potential for teratogenic or abortifacient effects; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
• Patients must not be receiving any other investigational agents

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Eastern Cooperative Oncology Group

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Cetuximab; Gemcitabine; Capecitabine; Radiotherapy; Radiation; Bevacizumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG Statistical Office

617-632-3012

Study Officials

• Jordan Berlin

  Eastern Cooperative Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2006
• First Posted: March 22, 2006
• Study Start: February 1, 2006
• Primary Completion: July 1, 2008
• Study Completion: February 1, 2012
• Last Updated: May 21, 2014
• Results First Posted: November 25, 2013

Record last verified: 2012-12

Locations

US (1)