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

NCT00047307 | Completed Phase 1

• 7 other identifiers: NCI-2012-0143002-057NCI-5764MSKCC-02057CDR0000257662U01CA069856R01CA067819
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

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

  6 weeks

Secondary Outcomes (2)

• Molecular correlates of apoptosis including PARP cleavage and caspase-3 activation, as well as changes in expression of p21, phosphorylation status of pRb and cyclin D1

  Baseline

• Molecular correlates of apoptosis including PARP cleavage and caspase-3 activation, as well as changes in expression of p21, phosphorylation status of pRb and cyclin D1

  10 weeks

Study Arms (1)

Treatment (alvocidib, gemcitabine hydrochloride, 3DRT)

EXPERIMENTAL

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)

Drug: alvocidib; Drug: gemcitabine hydrochloride; Radiation: 3-dimensional conformal radiation therapy; Other: laboratory biomarker analysis

Interventions

alvocidib DRUG

Given IV

Also known as: FLAVO, flavopiridol, HMR 1275, L-868275

Treatment (alvocidib, gemcitabine hydrochloride, 3DRT)

gemcitabine hydrochloride DRUG

Given IV

Also known as: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar

Treatment (alvocidib, gemcitabine hydrochloride, 3DRT)

3-dimensional conformal radiation therapy RADIATION

Undergo 3-dimensional conformal radiation therapy

Also known as: 3D conformal radiation therapy, 3D-CRT

Treatment (alvocidib, gemcitabine hydrochloride, 3DRT)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (alvocidib, gemcitabine hydrochloride, 3DRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

alvocidib; Gemcitabine; Radiotherapy, Conformal

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Gary K. Schwartz

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2002
• First Posted: January 27, 2003
• Study Start: August 1, 2002
• Primary Completion: August 1, 2008
• Last Updated: June 4, 2013

Record last verified: 2013-06

Locations

US (1)