Tipifarnib in Treating Patients With Metastatic Malignant Melanoma

Stage IV Melanoma Clinical Trial

Official title:

PHASE II TRIAL OF R115777 IN PATIENTS WITH METASTATIC MALIGNANT MELANOMA

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00060125
• Other study ID #: NCI-2012-02958
• Secondary ID: CALGB-500104CDR0
• Status: Completed
• Phase: Phase 2
• First received: May 6, 2003
• Last updated: June 4, 2013
• Start date: May 2003

Study information

• Verified date: June 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. primary completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Melanoma
• Recurrent Melanoma
• Stage IV Melanoma

Intervention

Drug:
• tipifarnib
Given orally

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Cancer and Leukemia Group B	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate (complete response [CR] and partial response [PR]}	Estimated confidence intervals will be adjusted for the number of stages.	Up to 2 years	No
Primary	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	No
Primary	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	No
Secondary	Correlation between RhoC expression levels and response		From baseline to up to 2 years	No
Secondary	Change in FTAse levels		From baseline to up to 2 years	No
Secondary	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	No
Secondary	Adverse events as assessed by Common Toxicity Criteria (CTC) version 2.0		Up to 2 years	Yes