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

Primary Purpose

Pancreatic Cancer

Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
conatumumab
capecitabine
gemcitabine hydrochloride
3-dimensional conformal radiation therapy
Sponsored by
Radiation Therapy Oncology Group
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer focused on measuring adenocarcinoma of the pancreas, stage III pancreatic cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Outcomes

    Primary Outcome Measures

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

    Secondary Outcome Measures

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

    Full Information

    First Posted
    November 20, 2009
    Last Updated
    June 21, 2013
    Sponsor
    Radiation Therapy Oncology Group
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01017822
    Brief Title
    Conatumumab, Gemcitabine Hydrochloride, Capecitabine, and Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer
    Official Title
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2013
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    This study was withdrawn due to study agent availability.
    Study Start Date
    undefined (undefined)
    Primary Completion Date
    undefined (undefined)
    Study Completion Date
    undefined (undefined)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Radiation Therapy Oncology Group
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pancreatic Cancer
    Keywords
    adenocarcinoma of the pancreas, stage III pancreatic cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Masking
    None (Open Label)
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Intervention Type
    Biological
    Intervention Name(s)
    conatumumab
    Intervention Type
    Drug
    Intervention Name(s)
    capecitabine
    Intervention Type
    Drug
    Intervention Name(s)
    gemcitabine hydrochloride
    Intervention Type
    Radiation
    Intervention Name(s)
    3-dimensional conformal radiation therapy
    Primary Outcome Measure Information:
    Title
    Dose-limiting toxicity (Phase I)
    Title
    Overall survival (Phase II)
    Secondary Outcome Measure Information:
    Title
    Adverse events (Phase I and II)
    Title
    Progression-free survival (Phase II)
    Title
    Response rate (Phase II)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Christopher H. Crane, MD
    Organizational Affiliation
    M.D. Anderson Cancer Center
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

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

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