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

This study has been completed.
Sponsor:
Collaborators:
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT01298401
First received: February 16, 2011
Last updated: July 9, 2014
Last verified: July 2014
  Purpose

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.


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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Induction AMG 479 and Gemcitabine, Followed by AMG 479, Capecitabine, and 3D-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 of ganitumab and capecitabine given concurrently with radiotherapy [ Time Frame: From start of chemoradiation to 21 days after the end of chemoradiation ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response rate (for patients treated at maximum-tolerated dose of ganitumab) [ Time Frame: Analysis occurs after all patients have been potentially followed for 1 year ] [ Designated as safety issue: No ]
  • Overall survival (for patients treated at maximum-tolerated dose of ganitumab) [ Time Frame: Analysis occurs after all patients have been potentially followed for 1 year ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: February 2012
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
Dose level -1A (Ganitumab 6 mg/kg, Capecitabine 825mg/m2)
Biological: ganitumab Drug: capecitabine Drug: gemcitabine hydrochloride Radiation: 3-dimensional conformal radiation therapy
Experimental: Arm B
Dose level 1A (Ganitumab 12 mg/kg, Capecitabine 825mg/m2)
Biological: ganitumab Drug: capecitabine Drug: gemcitabine hydrochloride Radiation: 3-dimensional conformal radiation therapy
Experimental: Arm C
Dose level 2A (Ganitumab 20 mg/kg, Capecitabine 825mg/m2)
Biological: ganitumab Drug: capecitabine Drug: gemcitabine hydrochloride Radiation: 3-dimensional conformal radiation therapy
Experimental: Arm D
Dose level -1B (Ganitumab 6 mg/kg, Capecitabine 625mg/m2)
Biological: ganitumab Drug: capecitabine Drug: gemcitabine hydrochloride Radiation: 3-dimensional conformal radiation therapy
Experimental: Arm E
Dose level 1B (Ganitumab 12 mg/kg, Capecitabine 625mg/m2)
Biological: ganitumab Drug: capecitabine Drug: gemcitabine hydrochloride Radiation: 3-dimensional conformal radiation therapy
Experimental: Arm F
Dose level 2B (Ganitumab 20 mg/kg, Capecitabine 625mg/m2)
Biological: ganitumab Drug: capecitabine Drug: gemcitabine hydrochloride Radiation: 3-dimensional conformal radiation therapy

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Pathologically confirmed (histologic or cytologic) locally advanced adenocarcinoma of the pancreas

    • Patients must have unresectable disease based on institutional standardized criteria of unresectability or medical inoperability
  • Patients with or without regional adenopathy are eligible
  • No distant metastases based upon the following minimum diagnostic workup:

    • History and/or physical examination, including collection of weight and vital signs, within 28 days prior to study entry
    • Abdominal and/or pelvic CT scan with IV contrast or MRI scan within 21 days prior to study entry
    • Chest CT scan or whole-body PET/CT within 21 days prior to study entry
  • No second malignancy or peritoneal seeding

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-1
  • Absolute neutrophil count (ANC) ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin (Hgb) ≥ 10.0 g/dL (the use of transfusion or other intervention to achieve Hgb ≥ 10.0 g/dL is acceptable)
  • Glycosylated hemoglobin (HgbA1c) ≤ 8%
  • Serum creatinine ≤ 1.5 mg/dL
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 3 times upper limit of normal (ULN)
  • Total bilirubin < 3.0 mg/dL
  • Alkaline phosphatase < 3 times ULN
  • Fasting blood glucose < 160 mg/dL

    • Patients with a non-fasting blood glucose > 160 mg/dL (8.9 mmol/L) must have a fasting blood glucose ≤ 160 mg/dL (8.9 mmol/L) in order to be eligible
  • No grade 2 or worse hearing impairment
  • Negative serum pregnancy test (if applicable)
  • Women of childbearing potential and men who are sexually active must be willing/able to use medically acceptable forms of contraception during the course of the study, and for 3 months (6 months for men) after the last study drug administration
  • Not pregnant or nursing
  • Ability to swallow oral medications
  • At least 3 years since prior malignancy except non-melanomatous skin cancer or carcinoma in situ of the breast, oral cavity, or cervix
  • No severe active co-morbidity, defined as any of the following:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
    • Transmural myocardial infarction within 6 months prior to study entry
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization, or precluding study therapy within 30 days before registration
    • 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
    • Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition

      • HIV testing is not required for entry into this protocol
    • Existing venous thromboembolism requiring anti-coagulation therapy
  • No prior allergic reaction to capecitabine or gemcitabine hydrochloride

PRIOR CONCURRENT THERAPY:

  • No prior systemic chemotherapy for pancreatic cancer

    • Prior chemotherapy for malignancies other than pancreatic cancer is allowed provided chemotherapy was completed > 3 years prior to study entry
  • No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • More than 28 days since any prior major surgery

    • Insertion of a vascular access device, insertion of a biliary stent, exploratory laparotomy, or laparoscopy are not considered major surgery
  • No prior ganitumab
  • Patients requiring concurrent oral anticoagulants (e.g., Coumadin, warfarin) are eligible provided there is increased vigilance with respect to monitoring international normalized ratio (INR)
  • No concurrent participation in another clinical treatment trial
  • No concurrent intensity-modulated radiotherapy
  • No other concurrent therapy including the following:

    • Other investigational or approved chemotherapeutic agents
    • Other monoclonal antibody
    • Sorivudine or brivudine A
    • Cimetidine
    • G-CSF agents
  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: NCT01298401

Locations
United States, California
St. Joseph Hospital Regional Cancer Center - Orange
Orange, California, United States, 92868
United States, Delaware
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
United States, Kentucky
James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, United States, 40202
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, New York
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, Ohio
Summa Center for Cancer Care at Akron City Hospital
Akron, Ohio, United States, 44309-2090
United States, Pennsylvania
McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
Reading, Pennsylvania, United States, 19612-6052
United States, Rhode Island
Northmain Radiation Oncology
Providence, Rhode Island, United States, 02904
Rhode Island Hospital Comprehensive Cancer Center
Providence, Rhode Island, United States, 02903
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
Radiation Therapy Oncology Group
NRG Oncology
Investigators
Principal Investigator: Christopher H. Crane, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT01298401     History of Changes
Other Study ID Numbers: RTOG 1102, CDR0000695567
Study First Received: February 16, 2011
Last Updated: July 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Radiation Therapy Oncology Group:
adenocarcinoma of the pancreas
stage IIB pancreatic cancer
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
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 October 19, 2014