Tipifarnib in Treating Patients With Metastatic Malignant Melanoma

PHASE II TRIAL OF R115777 IN PATIENTS WITH METASTATIC MALIGNANT MELANOMA

This phase II trial is studying how well tipifarnib works in treating patients with metastatic malignant melanoma. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.

Study Overview

• Status: Completed
• Conditions: Recurrent Melanoma; Stage IV Melanoma
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: tipifarnib

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate the clinical response rate in patients with metastatic malignant melanoma treated with R115777 (tipifarnib).

II. To evaluate the safety of R115777 in patients with metastatic melanoma.

SECONDARY OBJECTIVES:

I. To assess RhoC expression in tumor samples pre- and post- therapy with R115777.

II. To evaluate Ftase levels in peripheral blood and tumor samples pre- and post-therapy with R115777.

III. To assess the effect of R115777 treatment on T lymphocyte cytokine production, pre- and post- therapy with R115777.

IV. Estimate time to treatment failure (TTF). Time to treatment failure is defined as time to withdrawal for unacceptable toxicity or progressive disease.

OUTLINE Patients receive oral tipifarnib twice daily on days 1-21. Treatment repeats every 28 days for at least 2 courses and for a maximum of 2 years in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (CR) receive 2 additional courses beyond CR.

Patients who discontinue therapy due to toxicity or complete response are followed every 3 months for 2 years after study entry. Patients who discontinue therapy due to disease progression are followed every 6 months for 2 years after study entry. Patients with stable or partially responding disease who complete treatment are followed at 2 years after study entry.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60606
      • Cancer and Leukemia Group B

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:

• Histological or cytological diagnosis of cutaneous melanoma and clinical evidence of distant metastatic, non-resectable regional lymphatic, or extensive in transit recurrent disease

• Patients must have at least 2 cutaneous lesions amenable to excisional biopsy for correlative studies; in addition, patients must have measurable disease; the disease remaining after the first excisional biopsy must be measurable; lesions that are considered intrinsically non-measurable include the following:

  • Bone lesions
  • Leptomeningeal disease
  • Ascites
  • Pleural/pericardial effusion
  • Lymphangitis cutis/pulmonis
  • Abdominal masses that are not confirmed and followed by imaging techniques
  • Cystic lesions
  • Lesions that are situated in a previously irradiated area
• No history of brain metastases
• No allergies to azoles (e.g. ketoconazole) or allergies to compounds structurally similar to R115777

• No more than 1 prior immunotherapy regimen for treatment of advanced melanoma; an additional immunologic therapy in the adjuvant setting (e.g. IFN-a) is acceptable; prior chemotherapy for any stage of melanoma is not allowed

  • No radiotherapy or immunotherapy within four weeks prior to the initiation of therapy on this study
• CTC (ECOG) performance status 0-1
• Non-pregnant, non-nursing; treatment under this protocol would expose an unborn child to significant risks; women and men of reproductive potential should agree to use an effective means of birth control; women of child-bearing age will undergo pregnancy testing
• ANC >= 1500/uL
• Platelets >= 100,000/uL
• Bilirubin =< 1.5 mg/dL
• Creatinine =< 2.0 mg/dL

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); Patients receive oral tipifarnib twice daily on days 1-21. Treatment repeats every 28 days for at least 2 courses and for a maximum of 2 years in the absence of disease progression or unacceptable toxicity. Patients who achieve CR receive 2 additional courses beyond CR.	Other: laboratory biomarker analysis; Correlative studies; Drug: tipifarnib; Given orally; Other Names: R115777; Zarnestra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate (complete response [CR] and partial response [PR]}	Estimated confidence intervals will be adjusted for the number of stages.	Up to 2 years
Progression-free survival (PFS)	Estimated using the method of Kaplan and Meier.	From date of entry onto the trial until documented progression or death from any cause, assessed up to 2 years
Time to treatment failure (TTF)	Estimated using the method of Kaplan and Meier.	From trial entry until a patient ends protocol therapy due to unacceptable toxicity, progression or death from any cause, assessed up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between RhoC expression levels and response		From baseline to up to 2 years
Change in FTAse levels		From baseline to up to 2 years
Change in the production of IL-2 and IFN-g by T cells	Descriptive statistics will be used to describe the mean and spread of production of IL-2 and IFN-g.	From baseline to up to 2 years
Adverse events as assessed by Common Toxicity Criteria (CTC) version 2.0		Up to 2 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Thomas Gajewski, Cancer and Leukemia Group B

Publications and helpful links

General Publications

• Gajewski TF, Salama AK, Niedzwiecki D, Johnson J, Linette G, Bucher C, Blaskovich MA, Sebti SM, Haluska F; Cancer and Leukemia Group B. Phase II study of the farnesyltransferase inhibitor R115777 in advanced melanoma (CALGB 500104). J Transl Med. 2012 Dec 10;10:246. doi: 10.1186/1479-5876-10-246.

Study record dates

Study Major Dates

• Study Start: May 1, 2003
• Primary Completion (Actual): June 1, 2006

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Estimate): June 5, 2013
• Last Update Submitted That Met QC Criteria: June 4, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Antineoplastic Agents; Tipifarnib
• Other Study ID Numbers: NCI-2012-02958; U10CA031946 (U.S. NIH Grant/Contract); CALGB-500104; CDR0000299508