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Ganitumab and Gemcitabine Hydrochloride Followed by Radiation Therapy, Ganitumab, Capecitabine, and Maintenance Therapy in Treating Patients With Locally Advanced Cancer of the Pancreas

Phase 1
Completed
Conditions
Pancreatic Cancer
Interventions
Biological: ganitumab
Radiation: 3-dimensional conformal radiation therapy
Registration Number
NCT01298401
Lead Sponsor
Radiation Therapy Oncology Group
Brief Summary

RATIONALE: Monoclonal antibodies, such as ganitumab, 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 cancer-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. Specialized radiation therapy, such as 3-dimensional conformal radiation therapy, that delivers a high-dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue.

PURPOSE: This phase I trial is studying the side effects and best dose of ganitumab when given together with gemcitabine hydrochloride followed by radiation therapy, ganitumab, capecitabine, and maintenance therapy in treating patients with locally advanced cancer of the pancreas.

Detailed Description

OBJECTIVES:

Primary

* To evaluate the maximum dose of ganitumab, up to a target dose of 20 mg/kg, given concurrently with capecitabine and radiotherapy following induction ganitumab and gemcitabine hydrochloride in patients with locally advanced pancreatic cancer.

Secondary

* To evaluate the safety profile of induction therapy comprising ganitumab and gemcitabine hydrochloride, followed by ganitumab and concurrent chemoradiation, and subsequently by maintenance ganitumab and gemcitabine hydrochloride until disease progression in patients with locally advanced pancreatic cancer.

* To evaluate response and overall survival of patients treated at the maximum dose of ganitumab given concurrently with capecitabine and radiotherapy following induction ganitumab and subsequently followed by maintenance ganitumab and gemcitabine hydrochloride until disease progression.

OUTLINE: This is a multicenter, dose-escalation study of ganitumab followed by an expanded cohort study.

Induction therapy: Patients receive ganitumab IV over 1-2 hours on days 1 and 15 and gemcitabine hydrochloride IV over 30 minutes on days 1, 15, and 22. Treatment repeats every 28 days for 2 courses.

Concurrent therapy: Beginning 10-28 days later, patients undergo 3-dimensional conformal radiotherapy once daily, 5 days a week for 5.5 weeks beginning on day 1. Patients also receive concurrent ganitumab IV over 1-2 hours on days 1, 15, and 29 and capecitabine orally (PO) twice daily on days 1-5 weekly for 5.5 weeks.

Maintenance therapy: Beginning 21-42 days later, patients receive ganitumab IV over 1-2 hours on days 1 and 15 and gemcitabine hydrochloride IV over 30 minutes on days 1, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 2 years, every 4 months for 1 year, and then annually thereafter.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
8
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Arm Fgemcitabine hydrochlorideDose level 2B (Ganitumab 20 mg/kg, Capecitabine 625mg/m2)
Arm AganitumabDose level -1A (Ganitumab 6 mg/kg, Capecitabine 825mg/m2)
Arm C3-dimensional conformal radiation therapyDose level 2A (Ganitumab 20 mg/kg, Capecitabine 825mg/m2)
Arm EganitumabDose level 1B (Ganitumab 12 mg/kg, Capecitabine 625mg/m2)
Arm Egemcitabine hydrochlorideDose level 1B (Ganitumab 12 mg/kg, Capecitabine 625mg/m2)
Arm E3-dimensional conformal radiation therapyDose level 1B (Ganitumab 12 mg/kg, Capecitabine 625mg/m2)
Arm FganitumabDose level 2B (Ganitumab 20 mg/kg, Capecitabine 625mg/m2)
Arm FcapecitabineDose level 2B (Ganitumab 20 mg/kg, Capecitabine 625mg/m2)
Arm F3-dimensional conformal radiation therapyDose level 2B (Ganitumab 20 mg/kg, Capecitabine 625mg/m2)
Arm A3-dimensional conformal radiation therapyDose level -1A (Ganitumab 6 mg/kg, Capecitabine 825mg/m2)
Arm Cgemcitabine hydrochlorideDose level 2A (Ganitumab 20 mg/kg, Capecitabine 825mg/m2)
Arm Agemcitabine hydrochlorideDose level -1A (Ganitumab 6 mg/kg, Capecitabine 825mg/m2)
Arm CganitumabDose level 2A (Ganitumab 20 mg/kg, Capecitabine 825mg/m2)
Arm BganitumabDose level 1A (Ganitumab 12 mg/kg, Capecitabine 825mg/m2)
Arm Bgemcitabine hydrochlorideDose level 1A (Ganitumab 12 mg/kg, Capecitabine 825mg/m2)
Arm D3-dimensional conformal radiation therapyDose level -1B (Ganitumab 6 mg/kg, Capecitabine 625mg/m2)
Arm DganitumabDose level -1B (Ganitumab 6 mg/kg, Capecitabine 625mg/m2)
Arm DcapecitabineDose level -1B (Ganitumab 6 mg/kg, Capecitabine 625mg/m2)
Arm BcapecitabineDose level 1A (Ganitumab 12 mg/kg, Capecitabine 825mg/m2)
Arm B3-dimensional conformal radiation therapyDose level 1A (Ganitumab 12 mg/kg, Capecitabine 825mg/m2)
Arm CcapecitabineDose level 2A (Ganitumab 20 mg/kg, Capecitabine 825mg/m2)
Arm Dgemcitabine hydrochlorideDose level -1B (Ganitumab 6 mg/kg, Capecitabine 625mg/m2)
Arm AcapecitabineDose level -1A (Ganitumab 6 mg/kg, Capecitabine 825mg/m2)
Arm EcapecitabineDose level 1B (Ganitumab 12 mg/kg, Capecitabine 625mg/m2)
Primary Outcome Measures
NameTimeMethod
Dose-limiting toxicity of ganitumab and capecitabine given concurrently with radiotherapyFrom start of chemoradiation to 21 days after the end of chemoradiation
Secondary Outcome Measures
NameTimeMethod
Response rate (for patients treated at maximum-tolerated dose of ganitumab)Analysis occurs after all patients have been potentially followed for 1 year
Overall survival (for patients treated at maximum-tolerated dose of ganitumab)Analysis occurs after all patients have been potentially followed for 1 year

Trial Locations

Locations (10)

CCOP - Christiana Care Health Services

🇺🇸

Newark, Delaware, United States

James P. Wilmot Cancer Center at University of Rochester Medical Center

🇺🇸

Rochester, New York, United States

James Graham Brown Cancer Center at University of Louisville

🇺🇸

Louisville, Kentucky, United States

St. Joseph Hospital Regional Cancer Center - Orange

🇺🇸

Orange, California, United States

McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center

🇺🇸

Reading, Pennsylvania, United States

Rhode Island Hospital Comprehensive Cancer Center

🇺🇸

Providence, Rhode Island, United States

Northmain Radiation Oncology

🇺🇸

Providence, Rhode Island, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

🇺🇸

Baltimore, Maryland, United States

Summa Center for Cancer Care at Akron City Hospital

🇺🇸

Akron, Ohio, United States

M. D. Anderson Cancer Center at University of Texas

🇺🇸

Houston, Texas, United States

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