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

NCT01298401 | Completed Phase 1 DMC

• 2 other identifiers: RTOG 1102CDR0000695567
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 10

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.

Conditions

Pancreatic Cancer

Keywords

adenocarcinoma of the pancreas; stage IIB pancreatic cancer; stage III pancreatic cancer

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity of ganitumab and capecitabine given concurrently with radiotherapy

  From start of chemoradiation to 21 days after the end of chemoradiation

Secondary Outcomes (2)

• 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

Study Arms (6)

Arm A

EXPERIMENTAL

Dose level -1A (Ganitumab 6 mg/kg, Capecitabine 825mg/m2)

Biological: ganitumab; Drug: capecitabine; Drug: gemcitabine hydrochloride; Radiation: 3-dimensional conformal radiation therapy

Arm B

EXPERIMENTAL

Dose level 1A (Ganitumab 12 mg/kg, Capecitabine 825mg/m2)

Biological: ganitumab; Drug: capecitabine; Drug: gemcitabine hydrochloride; Radiation: 3-dimensional conformal radiation therapy

Arm C

EXPERIMENTAL

Dose level 2A (Ganitumab 20 mg/kg, Capecitabine 825mg/m2)

Biological: ganitumab; Drug: capecitabine; Drug: gemcitabine hydrochloride; Radiation: 3-dimensional conformal radiation therapy

Arm D

EXPERIMENTAL

Dose level -1B (Ganitumab 6 mg/kg, Capecitabine 625mg/m2)

Biological: ganitumab; Drug: capecitabine; Drug: gemcitabine hydrochloride; Radiation: 3-dimensional conformal radiation therapy

Arm E

EXPERIMENTAL

Dose level 1B (Ganitumab 12 mg/kg, Capecitabine 625mg/m2)

Biological: ganitumab; Drug: capecitabine; Drug: gemcitabine hydrochloride; Radiation: 3-dimensional conformal radiation therapy

Arm F

EXPERIMENTAL

Dose level 2B (Ganitumab 20 mg/kg, Capecitabine 625mg/m2)

Biological: ganitumab; Drug: capecitabine; Drug: gemcitabine hydrochloride; Radiation: 3-dimensional conformal radiation therapy

Interventions

ganitumab BIOLOGICAL

Arm A; Arm B; Arm C; Arm D; Arm E; Arm F

capecitabine DRUG

Arm A; Arm B; Arm C; Arm D; Arm E; Arm F

gemcitabine hydrochloride DRUG

Arm A; Arm B; Arm C; Arm D; Arm E; Arm F

3-dimensional conformal radiation therapy RADIATION

Arm A; Arm B; Arm C; Arm D; Arm E; Arm F

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Radiation Therapy Oncology Group: lead
• National Cancer Institute (NCI): collaborator
• NRG Oncology: collaborator

Study Sites (10)

St. Joseph Hospital Regional Cancer Center - Orange

Orange, California, 92868, United States

Location

CCOP - Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

James Graham Brown Cancer Center at University of Louisville

Louisville, Kentucky, 40202, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

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

Rochester, New York, 14642, United States

Location

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, 44309-2090, United States

Location

McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center

Reading, Pennsylvania, 19612-6052, United States

Location

Rhode Island Hospital Comprehensive Cancer Center

Providence, Rhode Island, 02903, United States

Location

Northmain Radiation Oncology

Providence, Rhode Island, 02904, United States

Location

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

ganitumab; Capecitabine; Gemcitabine; Radiotherapy, Conformal

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Christopher H. Crane, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2011
• First Posted: February 17, 2011
• Study Start: February 1, 2012
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: November 17, 2015

Record last verified: 2015-11

Locations

US (10)