Tipifarnib, Gemcitabine, and Cisplatin in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer

A Phase II Trial of R115777, a Farnesyl Transferase Inhibitor, in Combination With Gemcitabine and Cisplatin in Advanced Non-Small Cell Lung Cancer (NSCLC)

Phase II trial to study the effectiveness of combining tipifarnib with gemcitabine and cisplatin in treating patients who have stage III or stage IV non-small cell lung cancer. Drugs used in chemotherapy such as gemcitabine and cisplatin use different ways to stop tumor cells from dividing so they stop growing or die. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Combining tipifarnib with combination chemotherapy may kill more tumor cells.

Study Overview

• Status: Completed
• Conditions: Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: tipifarnib; Drug: gemcitabine hydrochloride; Drug: cisplatin

Detailed Description

PRIMARY OBJECTIVES:

I. To describe the response rate in non-small cell lung cancer (NSCLC) patients receiving combination therapy with R115777, gemcitabine, and cisplatin.

SECONDARY OBJECTIVES:

I. To estimate the time to event efficacy variables including: time to progressive disease, time to treatment failure, time to death of any cause.

II. To estimate the duration of response for responding patients. III. To characterize the toxicities of R115777, gemcitabine, and cisplatin in this patient population.

TERTIARY OBJECTIVES:

I. To evaluate the association between polymorphism expression in candidate genes and clinical endpoints and toxicity to R115777, gemcitabine, and cisplatin.

OUTLINE: This is a multicenter study.

Patients receive oral tipifarnib twice daily on days 1-14, gemcitabine IV over 30 minutes on days 1 and 8, and cisplatin IV over 2 hours on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients with at least stable disease may continue to receive oral tipifarnib alone twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 months for 2 years.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed NSCLC with one of the following classifications:

  • Stage IIIB with pleural effusion
  • Stage IIIB and not a candidate for combined modality treatment with radiation therapy and chemotherapy
  • Stage IV
• Measurable disease, defined as at least one lesion whose longest diameter can be accurately measured as >= 2.0 cm
• Absolute neutrophil count (ANC) >= 1500/mm^3
• PLT >= 100,000
• Hgb > 10.0 g/dL
• Direct bilirubin =< 1.5 x UNL
• Alkaline phosphatase =< 5 x UNL
• AST =< 3 x UNL
• Creatinine =< 1.5 x UNL
• ECOG Performance Status (PS) 0 or 1
• Capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent

Exclusion Criteria:

• Any of the following as this regimen may be harmful to a developing fetus or nursing child:

  • Pregnant women
  • Breastfeeding women
  • Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.)

• Any of the following prior therapies:

  • Prior chemotherapy for NSCLC (exception: therapies used as a radiosensitizer such as low-dose weekly cisplatin and carbo/taxol with XRT)
  • Prior radiation > 25% of bone marrow
  • Prior immunotherapy, biologic or gene therapy
• New York Heart Association classification III or IV
• CNS metastases
• Uncontrolled infection
• Any other severe, underlying diseases that are, in the judgment of the investigator, inappropriate for entry into this study
• Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinomas, or other cancer from which the patient has been disease-free for at least five years
• Pre-existing peripheral neuropathy (motor or sensory) > grade 1 per NCI Common Toxicity Criteria (CTC)
• Known peripheral vascular disease or a history of deep vein thrombosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (tipifarnib, gemcitabine, cisplatin); Patients receive oral tipifarnib twice daily on days 1-14, gemcitabine IV over 30 minutes on days 1 and 8, and cisplatin IV over 2 hours on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with at least stable disease may continue to receive oral tipifarnib alone twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Other: laboratory biomarker analysis; Correlative studies; Drug: tipifarnib; Given orally; Other Names: R115777; Zarnestra; Drug: gemcitabine hydrochloride; Given IV; Other Names: Gemzar; gemcitabine; dFdC; difluorodeoxycytidine hydrochloride; Drug: cisplatin; Given IV; Other Names: CDDP; DDP; CACP; CPDD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of confirmed tumor responses, defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart	Ninety-five percent confidence intervals for the true success proportion will be calculated.	Up to 18 weeks (6 courses)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival time	The distribution of survival time will be estimated using the method of Kaplan-Meier.	Time from registration to death due to any cause, assessed up to 2 years
Time to disease progression	The distribution of time to progression will be estimated using the method of Kaplan-Meier.	Time from registration to documentation of disease progression, assessed up to 2 years
Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented		Up to 2 years
Time to treatment failure		Time from the date of registration to the date at which the patient is removed from treatment due to progression, toxicity, or refusal, assessed up to 2 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Alex Adjei, Mayo Clinic

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (Actual): April 1, 2004

Study Registration Dates

• First Submitted: March 6, 2003
• First Submitted That Met QC Criteria: March 6, 2003
• First Posted (Estimate): March 7, 2003

Study Record Updates

• Last Update Posted (Estimate): June 4, 2013
• Last Update Submitted That Met QC Criteria: June 3, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Tipifarnib
• Other Study ID Numbers: NCI-2012-02808; N01CM17104 (U.S. NIH Grant/Contract); N01CM17102 (U.S. NIH Grant/Contract); MC0123