Flavopiridol Plus Radiation Therapy Followed By Gemcitabine Hydrochloride in Treating Patients With Locally Advanced, Unresectable Pancreatic Cancer

NCT ID: NCT00047307

Last Updated: 2013-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-08-31

Brief Summary

Drugs used in chemotherapy work different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Flavopiridol may make the tumor cells more sensitive to radiation therapy. Phase I trial to study the effectiveness of combining flavopiridol with radiation therapy followed by gemcitabine hydrochloride in treating patients who have locally advanced, unresectable pancreatic cancer.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of flavopiridol in combination with radiotherapy followed by gemcitabine in patients with locally advanced, unresectable pancreatic cancer.

II. Determine the toxicity of this regimen in these patients.

SECONDARY OBJECTIVES:

I. Determine the pharmacokinetics of flavopiridol in these patients. II. Determine, preliminarily, the therapeutic activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of flavopiridol.

Patients receive flavopiridol IV over 1 hour twice weekly (on days 1 and 4 or days 2 and 5) for 6 weeks. Concurrently, patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Four weeks after the completion of radiotherapy, patients are re-evaluated*. Beginning within 4-7 weeks after the completion of chemotherapy and radiotherapy, patients receive gemcitabine hydrochloride alone or in combination with another cytotoxic agent or gemcitabine hydrochloride combined with a targeted drug (e.g., erlotinib or bevacizumab) at the discretion of the oncologist. NOTE: *Patients whose imaging studies suggest potential curative resection are referred for a surgical evaluation before initiating gemcitabine hydrochloride therapy. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 10 additional patients are treated at the recommended phase II dose.

Patients are followed at 4 weeks and then every 8 weeks thereafter.

PROJECTED ACCRUAL: Approximately 3-46 patients will be accrued for this study within 2 years.

Conditions

Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage II Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (alvocidib, gemcitabine hydrochloride, 3DRT)

Patients receive flavopiridol IV over 1 hour twice weekly (on days 1 and 4 or days 2 and 5) for 6 weeks. Concurrently, patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Four weeks after the completion of radiotherapy, patients are re-evaluated*. Beginning within 4-7 weeks after the completion of chemotherapy and radiotherapy, patients receive gemcitabine hydrochloride alone or in combination with another cytotoxic agent or gemcitabine hydrochloride combined with a targeted drug (e.g., erlotinib or bevacizumab) at the discretion of the oncologist. NOTE: *Patients whose imaging studies suggest potential curative resection are referred for a surgical evaluation before initiating gemcitabine hydrochloride therapy. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. Continued (see detailed description)

Group Type: EXPERIMENTAL

alvocidib

Intervention Type: DRUG

Given IV

gemcitabine hydrochloride

Intervention Type: DRUG

Given IV

3-dimensional conformal radiation therapy

Intervention Type: RADIATION

Undergo 3-dimensional conformal radiation therapy

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

alvocidib

Given IV

Intervention Type: DRUG

gemcitabine hydrochloride

Given IV

Intervention Type: DRUG

3-dimensional conformal radiation therapy

Undergo 3-dimensional conformal radiation therapy

Intervention Type: RADIATION

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

FLAVO; flavopiridol; HMR 1275; L-868275; dFdC; difluorodeoxycytidine hydrochloride; gemcitabine; Gemzar; 3D conformal radiation therapy; 3D-CRT

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed adenocarcinoma of the pancreas

• No non-adenocarcinoma of the pancreas (i.e., islet cell, lymphoma, or sarcoma)
• Locally advanced and unresectable disease defined as the following:

• Obvious encasement of the celiac, hepatic, or superior mesenteric artery
• Encasement of the portal or superior mesenteric vein not amenable to resection
• Extrapancreatic extension with or without regional lymph node involvement
• No distant metastases
• Measurable or evaluable disease

• Primary pancreatic tumor is considered evaluable, not measurable
• A lymph node mass is considered measurable
• Performance status - ECOG 0-2
• Performance status - Karnofsky 60-100%
• More than 12 weeks
• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin no greater than 1.5 mg/dL
• AST and ALT no greater than 2.5 times upper limit of normal
• Creatinine no greater than 1.5 mg/dL
• Creatinine clearance at least 60 mL/min
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No Crohn's disease or inflammatory bowel disease that would preclude study participation
• No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
• No other uncontrolled concurrent illness that would preclude study participation
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior chemotherapy for this disease except gemcitabine hydrochloride-based therapy for which no radiologic evidence of distant metastatic disease exists
• No prior flavopiridol or other cyclin-dependent kinase therapies
• No prior radiotherapy for this disease
• Prior curative surgery with local recurrence allowed
• No other concurrent investigational therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gary K. Schwartz

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

02-057

Identifier Type: -

Identifier Source: secondary_id

NCI-5764

Identifier Type: -

Identifier Source: secondary_id

MSKCC-02057

Identifier Type: -

Identifier Source: secondary_id

CDR0000257662

Identifier Type: -

Identifier Source: secondary_id

U01CA069856

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01CA067819

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-01430

Identifier Type: -

Identifier Source: org_study_id