Cetuximab, Gemcitabine, and Oxaliplatin Followed By Surgery or External-Beam Radiation Therapy and Capecitabine in Treating Patients With Locally Advanced, Nonmetastatic Pancreatic Cancer That Cannot Be Removed By Surgery

• ClinicalTrials.gov Identifier: NCT00408564
• Recruitment Status: Completed
• First Posted: December 7, 2006
• Results First Posted: July 23, 2018
• Last Update Posted: July 23, 2018
• Sponsor: Medical University of South Carolina
• Information provided by (Responsible Party): Medical University of South Carolina

Tracking Information

• First Submitted Date: December 6, 2006
• First Posted Date: December 7, 2006
• Results First Submitted Date: May 23, 2018
• Results First Posted Date: July 23, 2018
• Last Update Posted Date: July 23, 2018
• Study Start Date: January 2006
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 19, 2018): Progression-free Survival at 6 Months [ Time Frame: up to 46 weeks after the start of study treatment ]
• Original Primary Outcome Measures (submitted: December 6, 2006): Progression-free Survival at 6 Months
• Change History: Complete list of historical versions of study NCT00408564 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: July 19, 2018)

• Number of Participants With Grade 3-4 Adverse Events Reported [ Time Frame: from start of study treatment until end of study visit, about 30 weeks ]
• Overall Survival [ Time Frame: up to 46 weeks after the start of study treatment ]
• Response Rate [ Time Frame: up to 46 weeks after the start of study treatment ]
  defined as the total number of subjects whose best response is PR or CR.
• Response Duration in Patients With at Least Partial Response to Treatment [ Time Frame: up to 46 weeks after the start of study treatment ]
• Determine the Biomarker Response of CA 19-9 to Therapy [ Time Frame: from start up treatment to one year after end of treatment, up to 81 weeks ]

Original Secondary Outcome Measures (submitted: December 6, 2006)

• Toxicity
• Overall survival and progression-free survival
• Response Rate
• Response duration in patients with at least partial response

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Cetuximab, Gemcitabine, and Oxaliplatin Followed By Surgery or External-Beam Radiation Therapy and Capecitabine in Treating Patients With Locally Advanced, Nonmetastatic Pancreatic Cancer That Cannot Be Removed By Surgery
• Official Title: Phase II Study of Neoadjuvant Gemcitabine/Oxaliplatin and Cetuximab Followed by Surgery or Concurrent External Beam Radiation With Capecitabine for Patients With Locally Advanced Unresectable Nonmetastatic Pancreatic Cancer

Brief Summary

RATIONALE: Monoclonal antibodies, such as 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. Drugs used in chemotherapy, such as gemcitabine, oxaliplatin, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sometimes when chemotherapy is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to chemotherapy. Giving cetuximab together with chemotherapy may reduce drug resistance and allow the tumor cells to be killed. Giving cetuximab and chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Radiation therapy uses high-energy x-rays to kill tumor cells.

PURPOSE: This phase II trial is studying how well giving cetuximab together with oxaliplatin and gemcitabine followed by surgery or external-beam radiation therapy and capecitabine works in treating patients with locally advanced, nonmetastatic pancreatic cancer that cannot be removed by surgery.

Detailed Description

OBJECTIVES:

Primary

• Determine the progression-free survival rate in patients with unresectable, locally advanced, nonmetastatic adenocarcinoma of the pancreas treated with neoadjuvant therapy comprising cetuximab, gemcitabine hydrochloride, and oxaliplatin followed by either surgery or chemoradiotherapy comprising external-beam radiotherapy and capecitabine.

Secondary

• Determine the toxicity and tolerability of this regimen in these patients.
• Determine overall survival and progression-free survival.
• Determine the response rate in these patients.
• Determine the response duration (defined as the time from first observation response to the time of progressive disease) in patients who achieve at least a partial response to treatment.
• Determine the biomarker response of CA19-9.

OUTLINE: This is an open-label study.

• Neoadjuvant therapy: Patients receive cetuximab IV over 1-2 hours on days 1 and 8, gemcitabine hydrochloride IV over 100 minutes on day 1, and oxaliplatin IV over 2 hours on day 2. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are evaluated after completion of neoadjuvant therapy. Patients with metastatic disease are taken off study. Beginning within 4 weeks after completion of neoadjuvant therapy, patients with resectable disease proceed to surgical resection or chemoradiotherapy (by choice); patients with unresectable disease proceed to chemoradiotherapy.

• Surgery: Patients undergo surgical resection with the Whipple procedure.
• Chemoradiotherapy: Patients receive oral capecitabine twice daily 5 days a week (on days 1-5) and undergo external-beam radiotherapy once daily 5 days a week for 5½ weeks.

After completion of study treatment, patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pancreatic Cancer

Intervention

• Biological: cetuximab
• Drug: capecitabine
• Drug: oxaliplatin
• Procedure: conventional surgery
• Radiation: radiation therapy
• Drug: Gemcitabine

Study Arms

Experimental: Gemcitabine,Oxaliplatin and Cetuximab

Gemcitabine will be given on day 1 of every 2 week cycle. Oxaliplatin will be given day 2 of every 2 week cycle. Cetuximab will be given every week for 12 weeks.

After chemotherapy, patient will be assessed for resectability. Patients will have either surgery or daily radiation and capceitabine Monday-Friday for a total of 5 and a half weeks.

Interventions:

• Biological: cetuximab
• Drug: capecitabine
• Drug: oxaliplatin
• Procedure: conventional surgery
• Radiation: radiation therapy
• Drug: Gemcitabine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 6, 2018): 39
• Original Enrollment (submitted: December 6, 2006): 42
• Actual Study Completion Date: April 2013
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically or radiologically confirmed pancreatic cancer, meeting both of the following criteria:

  • Locally advanced, nonmetastatic disease
  • Surgically unresectable disease

• Measurable disease, defined as unidimensionally measurable by physical exam or imaging study

  • The following are considered nonmeasurable disease:

    • Bone-only disease
    • Pleural or peritoneal effusions
    • CNS lesions
    • Irradiated lesions in the absence of progression after radiotherapy
• No history or evidence of CNS disease
• No metastatic disease to distant organs (e.g., liver, lung, brain, or bone)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 2.0 mg/dL
• Creatinine ≤ 2.0 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 90 days after completion of study therapy
• No acute hepatitis
• No known HIV positivity
• No active or uncontrolled infection

• No significant history of uncontrolled cardiac disease, including, but not limited to, any of the following:

  • Uncontrolled hypertension
  • Unstable angina
  • Myocardial infarction within the past 6 months
  • Uncontrolled congestive heart failure
  • Cardiomyopathy with decreased ejection fraction
• No prior severe infusion reaction to a monoclonal antibody
• No active second malignancy other than nonmelanoma skin cancer
• No history of deep vein thrombosis
• No history of bleeding diathesis or coagulopathy
• No other severe concurrent disease, mental incapacitation, or psychiatric illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

• No prior therapy for pancreatic cancer
• No prior therapy specifically targeting the epidermal growth factor-receptor pathway
• No major surgical procedure or open biopsy within the past 28 days
• No prior radiotherapy or chemotherapy
• No prior or concurrent full-dose anticoagulants or thrombolytics

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 120 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00408564
• Other Study ID Numbers: CDR0000518313; MUSC-100918; BMS-MUSC-100918; SANOFI-MUSC-100918
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Medical University of South Carolina
• Study Sponsor: Medical University of South Carolina
• Collaborators: Not Provided

Investigators

• Principal Investigator: Andrew S. Kraft, MD; Medical University of South Carolina
• Study Chair: Gustavo Leone; Medical University of South Carolina, Hollings Cancer Center

• PRS Account: Medical University of South Carolina
• Verification Date: May 2018