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

Sponsor

Radiation Therapy Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT01298401

Collaborator

National Cancer Institute (NCI) (NIH), NRG Oncology (Other)

Enrollment

Locations

Arms

Duration (Months)

0.8

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

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

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

8 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Feb 1, 2012

Actual Primary Completion Date :

Nov 1, 2013

Actual Study Completion Date :

Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

Dose-limiting toxicity of ganitumab and capecitabine given concurrently with radiotherapy [From start of chemoradiation to 21 days after the end of chemoradiation]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	St. Joseph Hospital Regional Cancer Center - Orange	Orange	California	United States	92868
2	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
3	James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky	United States	40202
4	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
5	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
6	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio	United States	44309-2090
7	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania	United States	19612-6052
8	Rhode Island Hospital Comprehensive Cancer Center	Providence	Rhode Island	United States	02903
9	Northmain Radiation Oncology	Providence	Rhode Island	United States	02904
10	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009