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

Sponsor

Radiation Therapy Oncology Group (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01017822

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as conatumumab, 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 tumor-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. Radiation therapy may uses high energy x-rays to kill tumor cells. Giving conatumumab together with gemcitabine hydrochloride, capecitabine, and radiation therapy may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of conatumumab when given together with gemcitabine hydrochloride, capecitabine, and radiation therapy and to see how well they work in treating patients with locally advanced pancreatic cancer.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer	Biological: conatumumab Drug: capecitabine Drug: gemcitabine hydrochloride Radiation: 3-dimensional conformal radiation therapy	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Primary

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

Secondary

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

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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

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