A Phase 1 Study of Alvocidib (Flavopiridol) in Combination With Radiation in Locally Advanced, Non-Operable Pancreatic and Extrahepatic Bile Duct Cancers


Phase 1
18 Years
N/A
Not Enrolling
Both
Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage II Pancreatic Cancer, Stage III Pancreatic Cancer, Stage IV Pancreatic Cancer

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Trial Information

A Phase 1 Study of Alvocidib (Flavopiridol) in Combination With Radiation in Locally Advanced, Non-Operable Pancreatic and Extrahepatic Bile Duct Cancers


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of flavopiridol when administered biweekly in conjunction with radiation for patients with locally advanced pancreatic or extrahepatic bile duct cancer

Outcome Time Frame:

6 weeks

Safety Issue:

Yes

Principal Investigator

Gary K. Schwartz

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01430

NCT ID:

NCT00047307

Start Date:

August 2002

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Pancreas
  • Recurrent Pancreatic Cancer
  • Stage II Pancreatic Cancer
  • Stage III Pancreatic Cancer
  • Stage IV Pancreatic Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Pancreatic Neoplasms

Name

Location
Memorial Sloan-Kettering Cancer Center New York, New York  10021