Conatumumab, Gemcitabine Hydrochloride, Capecitabine, and Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer

June 21, 2013 updated by: Radiation Therapy Oncology Group

A Phase I/II Study of Induction Conatumumab and Gemcitabine, Followed by Conatumumab, Capecitabine and 3-D Conformal Radiation Therapy (3D-CRT) With Subsequent Maintenance Therapy for Locally Advanced Pancreatic Cancer

RATIONALE: Monoclonal antibodies, such as conatumumab, 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 hydrochloride 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 may uses high energy x-rays to kill tumor cells. Giving conatumumab together with gemcitabine hydrochloride, capecitabine, and radiation therapy may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of conatumumab when given together with gemcitabine hydrochloride, capecitabine, and radiation therapy and to see how well they work in treating patients with locally advanced pancreatic cancer.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • To evaluate the maximum tolerated dose of conatumumab up to a target dose of 10 mg/kg given concurrently with capecitabine and radiotherapy following induction therapy comprising conatumumab and gemcitabine hydrochloride in patients with locally advanced pancreatic cancer. (Phase I)
  • To evaluate the overall survival of patients treated with this regimen. (Phase II)

Secondary

  • To evaluate the safety profile in patients treated with this regimen. (Phase I and II)
  • To evaluate the progression-free survival of patients treated with this regimen. (Phase II)
  • To evaluate the primary tumor response rate in patients treated with this regimen. (Phase II)
  • To generate translational research hypotheses. (Phase II)

OUTLINE: This is a multicenter, phase I dose-escalation study of conatumumab, followed by a phase II study.

  • Induction therapy: Patients receive conatumumab IV over 30-60 minutes on days 1 and 15 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 2 courses.
  • Conatumumab and chemoradiotherapy: Beginning 14-42 days after the last course of induction therapy, patients undergo 3-dimensional radiotherapy once daily, 5 days a week, for 5½ weeks (28 treatments). Patients also receive conatumumab IV over 30-60 minutes on days 1, 15, and 29 and oral capecitabine twice daily, 5 days a week, for 5½ weeks.
  • Maintenance therapy: Beginning 28-56 days after completion of chemoradiotherapy, patients receive conatumumab IV over 30-60 minutes on days 1 and 15 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Study Type

Interventional

Phase

  • Phase 2
  • Phase 1

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed adenocarcinoma of the pancreas

    • Locally advanced disease
    • With and without regional adenopathy
  • Unresectable disease based on institutional standardized criteria of unresectability OR medically inoperable
  • No distant metastatic disease, second malignancy, or peritoneal seeding

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-1
  • Absolute granulocyte count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention allowed)
  • Serum creatinine ≤ 1.5 mg/dL
  • ALT or AST < 3 times upper limit of normal (ULN)
  • Total bilirubin < 3.0 mg/dL
  • Alkaline phosphatase < 3 times ULN
  • Amylase ≤ 2 times ULN
  • Lipase ≤ 2 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 3 months after the last study drug administration (for women) or for ≥ 6 months after the last study drug administration (for men)
  • Able to swallow oral medications
  • No other invasive malignancy within the past 2 years, except for nonmelanomatous skin cancer or carcinoma in situ of the breast, oral cavity, or cervix

  • No severe, active co-morbidity, including any of the following:

    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within the past 30 days
    • Transmural myocardial infarction within the past 3 months
    • Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
    • Any other cardiac condition that, in the opinion of the treating physician, would make study treatment unreasonably hazardous for the patient
    • Acute bacterial or fungal infection requiring IV antibiotics
    • Uncontrolled malabsorption syndrome significantly affecting gastrointestinal function
    • Any unresolved bowel or bile duct obstruction
    • Major resection of the stomach or small bowel that could affect the absorption of capecitabine

    • AIDS based upon current CDC definition

      • HIV testing is not required for study entry
  • No prior allergic reaction to capecitabine or gemcitabine hydrochloride

PRIOR CONCURRENT THERAPY:

  • No prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields
  • No prior treatment with TRAIL-receptor agonists
  • No prior systemic chemotherapy for pancreatic cancer
  • More than 2 years since prior chemotherapy for malignancies other than pancreatic cancer

  • More than 28 days since prior major surgery (e.g., biliary or gastric bypass)

    • Insertion of a vascular access device, exploratory laparotomy, or laparoscopy are not considered major surgery
  • No concurrent intensity-modulated radiotherapy
  • No other concurrent chemotherapy
  • No other concurrent monoclonal antibody therapy
  • No concurrent sorivudine, brivudine A, or cimetidine
  • No concurrent participation in another clinical trial
  • Concurrent oral anticoagulants (e.g., warfarin) allowed provided INR is monitored

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Overall survival (Phase II)
Dose-limiting toxicity (Phase I)

Secondary Outcome Measures

Outcome Measure
Progression-free survival (Phase II)
Response rate (Phase II)
Adverse events (Phase I and II)

Collaborators and Investigators

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

Sponsor

Radiation Therapy Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Christopher H. Crane, MD, M.D. Anderson Cancer Center

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

First Submitted

November 20, 2009

First Submitted That Met QC Criteria

November 20, 2009

First Posted (Estimate)

November 23, 2009

Study Record Updates

Last Update Posted (Estimate)

June 24, 2013

Last Update Submitted That Met QC Criteria

June 21, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RTOG-0932
  • CDR0000659527

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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