Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Objectives

Primary

1. 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)
2. To evaluate the overall survival of patients treated with this regimen. (Phase II)

Secondary

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

Entry 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

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

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

Expected Enrollment

Outcomes

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

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

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

Christopher Crane, MD, Principal investigator		Ph: 713-563-2340; 800-392-1611

Registry Information
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
Trial Start Date		2009-11-01 (estimated)
Trial Completion Date		2010-11-01 (estimated)
Registered in ClinicalTrials.gov		NCT01017822
Date Submitted to PDQ		2009-11-16
Information Last Verified		2010-03-25
NCI Grant/Contract Number		CA21661

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