Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	MSKCC-02057 NCI-5764, NCT00047307, 5764

Objectives

1. Determine the maximum tolerated dose of flavopiridol in combination with radiotherapy followed by gemcitabine in patients with locally advanced, unresectable pancreatic cancer.
2. Determine the toxicity of this regimen in these patients.
3. Determine the pharmacokinetics of flavopiridol in these patients.
4. Determine, preliminarily, the therapeutic activity of this regimen in these patients.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• 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

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for this disease

Surgery

• Prior curative surgery with local recurrence allowed

Other

• No other concurrent investigational therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

  OR

• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• WBC at least 3,000/mm³
• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• AST and ALT no greater than 2.5 times upper limit of normal

Renal

• Creatinine no greater than 1.5 mg/dL

  OR

• Creatinine clearance at least 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Gastrointestinal

• 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

Other

• 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

Expected Enrollment

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

Outcomes

Recommended phase II dose as assessed by NCI toxicity scale during 5.5 weeks of treatment

Response as assessed by RECIST criteria at 8 weeks

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 alone or in combination with another cytotoxic agent or gemcitabine 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 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.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Gary K. Schwartz, MD, Protocol chair		Ph: 212-639-8324; 800-525-2225
Eileen O'Reilly, MD, Protocol co-chair		Ph: 212-639-6672; 800-525-2225 Email: oreillye@mskcc.org

Registry Information
Official Title		A Phase I Study Of Alvocidib (Flavopiridol) In Combination With Radiation In Locally Advanced, Non-Operable Pancreatic Cancer
Trial Start Date		2002-08-14
Trial Completion Date		2008-08-26
Registered in ClinicalTrials.gov		NCT00047307
Date Submitted to PDQ		2002-08-30
Information Last Verified		2008-03-30
NCI Grant/Contract Number		CA67819, CA08748

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