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

This study has been withdrawn prior to enrollment.
(This study was withdrawn due to study agent availability.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT01017822
First received: November 20, 2009
Last updated: June 21, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Pancreatic Cancer
Biological: conatumumab
Drug: capecitabine
Drug: gemcitabine hydrochloride
Radiation: 3-dimensional conformal radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Dose-limiting toxicity (Phase I) [ Designated as safety issue: Yes ]
  • Overall survival (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Adverse events (Phase I and II) [ Designated as safety issue: Yes ]
  • Progression-free survival (Phase II) [ Designated as safety issue: No ]
  • Response rate (Phase II) [ Designated as safety issue: No ]

Enrollment: 0
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01017822

Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Principal Investigator: Christopher H. Crane, MD M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT01017822     History of Changes
Other Study ID Numbers: RTOG-0932, CDR0000659527
Study First Received: November 20, 2009
Last Updated: June 21, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Radiation Therapy Oncology Group:
adenocarcinoma of the pancreas
stage III pancreatic cancer

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Capecitabine
Fluorouracil
Antibodies, Monoclonal
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 20, 2014