Tipifarnib in Treating Patients With Metastatic Malignant Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00060125
First received: May 6, 2003
Last updated: June 4, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Recurrent Melanoma
Stage IV Melanoma
Drug: tipifarnib
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: PHASE II TRIAL OF R115777 IN PATIENTS WITH METASTATIC MALIGNANT MELANOMA

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate (complete response [CR] and partial response [PR]} [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Estimated confidence intervals will be adjusted for the number of stages.

  • Progression-free survival (PFS) [ Time Frame: From date of entry onto the trial until documented progression or death from any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan and Meier.

  • Time to treatment failure (TTF) [ Time Frame: From trial entry until a patient ends protocol therapy due to unacceptable toxicity, progression or death from any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan and Meier.


Secondary Outcome Measures:
  • Correlation between RhoC expression levels and response [ Time Frame: From baseline to up to 2 years ] [ Designated as safety issue: No ]
  • Change in FTAse levels [ Time Frame: From baseline to up to 2 years ] [ Designated as safety issue: No ]
  • Change in the production of IL-2 and IFN-g by T cells [ Time Frame: From baseline to up to 2 years ] [ Designated as safety issue: No ]
    Descriptive statistics will be used to describe the mean and spread of production of IL-2 and IFN-g.

  • Adverse events as assessed by Common Toxicity Criteria (CTC) version 2.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 40
Study Start Date: May 2003
Primary Completion Date: June 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: tipifarnib
Given orally
Other Names:
  • R115777
  • Zarnestra
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00060125

Locations
United States, Illinois
Cancer and Leukemia Group B
Chicago, Illinois, United States, 60606
Sponsors and Collaborators
Investigators
Principal Investigator: Thomas Gajewski Cancer and Leukemia Group B
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00060125     History of Changes
Other Study ID Numbers: NCI-2012-02958, CALGB-500104, CDR0000299508, U10CA031946
Study First Received: May 6, 2003
Last Updated: June 4, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Tipifarnib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014