Clinical trial NCT00060125: Tipifarnib in Treating Patients With Metastatic Malignant Melanoma
Official title: PHASE II TRIAL OF R115777 IN PATIENTS WITH METASTATIC MALIGNANT MELANOMA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Melanoma
Stage IV Melanoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-05-07
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Response rate (complete response [CR] and partial response [PR]}
timeFrame: Up to 2 years
measure: Progression-free survival (PFS)
timeFrame: From date of entry onto the trial until documented progression or death from any cause, assessed up to 2 years
measure: Time to treatment failure (TTF)
timeFrame: 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 outcomes:
measure: Correlation between RhoC expression levels and response
timeFrame: From baseline to up to 2 years
measure: Change in FTAse levels
timeFrame: From baseline to up to 2 years
measure: Change in the production of IL-2 and IFN-g by T cells
timeFrame: From baseline to up to 2 years
measure: Adverse events as assessed by Common Toxicity Criteria (CTC) version 2.0
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Cancer and Leukemia Group B
state: Illinois
Study officials:
affiliation: Cancer and Leukemia Group B
name: Thomas Gajewski
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.