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

Sponsor:	Memorial Sloan-Kettering Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00047307

Purpose

RATIONALE: 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.

PURPOSE: Phase I trial to study the effectiveness of combining flavopiridol with radiation therapy followed by gemcitabine in treating patients who have locally advanced, unresectable pancreatic cancer.

Condition	Intervention	Phase
Pancreatic Cancer	Drug: alvocidib Drug: gemcitabine hydrochloride Radiation: radiation therapy	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Study Of Alvocidib (Flavopiridol) In Combination With Radiation In Locally Advanced, Non-Operable Pancreatic Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Gemcitabine Gemcitabine hydrochloride Alvocidib Flavopiridol

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Recommended phase II dose as assessed by NCI toxicity scale during 5.5 weeks of treatment [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Response as assessed by RECIST criteria at 8 weeks [ Designated as safety issue: No ]

Estimated Enrollment:	46
Study Start Date:	August 2002
Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose of flavopiridol in combination with radiotherapy followed by gemcitabine in patients with locally advanced, unresectable pancreatic cancer.
Determine the toxicity of this regimen in these patients.
Determine the pharmacokinetics of flavopiridol in these patients.
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 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.

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

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/mm^3
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00047307

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021-0009

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:	Gary K. Schwartz, MD	Memorial Sloan-Kettering Cancer Center
Investigator:	Eileen O'Reilly, MD	Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000257662, MSKCC-02057, NCI-5764
Study First Received:	October 3, 2002
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00047307 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the pancreas
recurrent pancreatic cancer
stage II pancreatic cancer
stage III pancreatic cancer
stage IV pancreatic cancer

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Pancreatic Neoplasms
Physiological Effects of Drugs
Protein Kinase Inhibitors
Neoplasms by Site
Therapeutic Uses
Growth Inhibitors
Gemcitabine

Endocrine Gland Neoplasms
Digestive System Neoplasms
Growth Substances
Endocrine System Diseases
Enzyme Inhibitors
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Flavopiridol
Neoplasms
Digestive System Diseases
Radiation-Sensitizing Agents
Pancreatic Diseases

ClinicalTrials.gov processed this record on November 27, 2009