Clinical trial NCT00026104: Combination Chemotherapy Plus Radiation Therapy With or Without Tipifarnib in Treating Patients With Locally Advanced Pancreatic Cancer
Official title: A Randomized Phase II Trial of Weekly Gemcitabine, Paclitaxel and External Irradiation (50.4 GY) Followed by the Farnesyl Transferase Inhibitor R115777 (NSC #702818) for Locally Advanced Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adenocarcinoma of the Pancreas
Stage II Pancreatic Cancer
Stage III Pancreatic Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: NRG Oncology
First posted: 2003-01-27
Enrollment: 154
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Randomized phase II trial to compare the effectiveness of gemcitabine, paclitaxel, and radiation therapy with or without tipifarnib in treating patients who have locally advanced pancreatic cancer. Drugs used in chemotherapy use 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. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Combining chemotherapy and radiation therapy with tipifarnib may be an effective treatment for pancreatic cancer.

Detailed description: OBJECTIVES:

I. Compare the 1-year survival rate in patients with locally advanced pancreatic cancer treated with paclitaxel, gemcitabine, and radiotherapy with or without tipifarnib.

II. Determine the toxicity and loco-regional activity of this chemoradiotherapy regimen in these patients.

III. Determine the feasibility and toxicity of prolonged administration of tipifarnib after chemoradiotherapy in these patients.

IV. Determine whether tipifarnib administered after chemoradiotherapy can increase progression-free and overall survival in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to weight loss in the preceding 6 months (more than 10% vs 10% or less) and tumor dimension (at least 5 cm vs less than 5 cm). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive radiotherapy once daily, 5 days a week, for 5.5 weeks, beginning on day 1. Patients also receive paclitaxel IV over 1 hour and gemcitabine IV over 30 minutes on days 1, 8, 15, 22, 29, and 36.

Arm II: Patients receive chemoradiotherapy as in arm I. Within 3-8 weeks after completion of chemoradiotherapy, patients without disease progression receive oral tipifarnib twice daily for 21 days.

Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed unresectable, locally advanced adenocarcinoma of the pancreas

  * Residual disease after resection (R1 or R2, microscopic or macroscopic) allowed
* No metastases in major viscera
* No peritoneal seeding or ascites
* Biliary or gastroduodenal obstruction must have drainage before starting study therapy
* Radiographically assessable disease encompassable within a single irradiation field (15 by 15 cm maximum)
* Performance status - Zubrod 0-1
* Granulocyte count at least 1,800/mm\^3
* Platelet count at least 100,000/mm\^3
* ALT less than 3 times upper limit of normal
* Bilirubin less than 2.0 mg/dL
* Creatinine less than 3.0 mg/dL
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No other malignancy within the past 2 years except non-melanoma skin cancer or carcinoma in situ of the cervix, uterus, or bladder
* No significant infection or other medical condition that would preclude study
* No prior chemotherapy (including gemcitabine or paclitaxel) for pancreatic cancer
* No other concurrent cytotoxic agents
* See Disease Characteristics
* No prior radiotherapy to the planned field
* No other concurrent radiotherapy
* See Disease Characteristics
* No other concurrent investigational agents

Primary outcomes:
measure: Overall survival
timeFrame: 1 year
Secondary outcomes:
measure: Frequency of patients developing unacceptable toxicity defined as grade 3 or higher gastrointestinal or pulmonary toxicity and/or discontinuation of treatment
timeFrame: Up to 5 years
measure: Difference in overall survival between treatment regimens
timeFrame: 1 year
measure: Progression-free survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Radiation Therapy Oncology Group
state: Pennsylvania
Study officials:
affiliation: Radiation Therapy Oncology Group
name: Tyvin Rich
role: PRINCIPAL_INVESTIGATOR
References: