Clinical trial NCT00448721: A Phase II Trial of Perifosine Following Tyrosine Kinase Inhibitor (TKI) - Failure in Patients With Renal Cancer
Official title: A Phase II Trial of Perifosine Following Tyrosine Kinase Inhibitor Failure in Patients With Advanced Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Renal Cell Carcinoma
Keywords: renal cell carcinoma
tyrosine kinase inhibitor failure
Lead sponsor: AEterna Zentaris
Sponsor class: INDUSTRY
Collaborators: name: Dana-Farber Cancer Institute
First posted: 2007-03-19
Enrollment: 24
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 is a single-arm phase II trial of perifosine in renal cancer patients who have experienced disease progression after receiving either sorafenib or sunitinib.

Detailed description: This is a single-arm phase II trial assessing the antitumor activity as measured by progression free survival of perifosine in patients with metastatic RCC who have progressed on sorafenib or sunitinib. A total of 48 patients will be enrolled in the trial. All subjects will have histologically confirmed metastatic RCC with predominantly clear cell features (≤ 50% other histologic features). Patients who have been taken off sorafenib or sunitinib may only have been off therapy for less than three months prior to study enrollment. Patients who remain on sorafenib or sunitinib may continue on drug at their current dose until two weeks prior to the initiation of perifosine therapy.

The study consists of three periods: pre-treatment/screening, treatment, and follow-up. Day 1 will be defined as the first day of perifosine therapy. Patients will remain in the treatment phase until progression or toxicity. Patients will be seen by an MD every 3 weeks with 6 weeks defining one cycle of therapy. Tumor evaluations will occur every 6 weeks.

Eligibility criteria: Inclusion Criteria:

* Patients will be required to have clear cell renal cell carcinoma with less than 50% of any other histology (papillary or chromophobe or oncocytic). There must be histologic confirmation by the treating center of either the primary or a metastatic lesion
* Patients must have experienced disease progression by RECIST criteria while on sorafenib or sunitinib
* Patients must be off of sorafenib or sunitinib for \>= 2 weeks prior to initiation of perifosine and \<= 3 months prior to enrollment
* Patients may have had sorafenib or sunitinib in the adjuvant setting as long as they have experienced disease recurrence while on therapy
* Patients must have measurable disease that is not curable by standard radiation therapy or surgery
* Age \>= 18 years
* ECOG performance status 0 or 1
* - Patients must have the ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

* History or clinical evidence of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastasis, or history of stroke
* Other than sorafenib or sunitinib, patients may have only had prior immunotherapy for stage IV disease
* Patients may have had prior sorafenib OR sunitinib and cannot have been treated with both TKIs
* Patients who have stopped sorafenib or sunitinib due to toxicity but have only progressed off therapy will not be allowed
* Patients may have had prior anti-angiogenic such as bevacizumab only if given in combination with either sorafenib or sunitinib
* Prior Thalidomide or IFNα are allowed for adjuvant therapy or stage IV disease
* Patients may not have had prior mTOR inhibitors (CCI-779, RAD001)

Primary outcomes:
measure: To estimate the progression free survival
timeFrame: Every 6 weeks
Secondary outcomes:
measure: To determine the objective response rate of perifosine
timeFrame: Every 6 weeks
measure: To investigate the tolerability and toxicity
timeFrame: Every 6 weeks
measure: To investigate surrogates of biologic target inhibition
timeFrame: Every 6 weeks
measure: To collect pre-treatment tissue specimens
timeFrame: Every 6 weeks
measure: To follow levels of pro-angiogenic cytokines
timeFrame: Every 6 weeks
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Investigative Site
state: California
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Philadelphia
country: United States
facility: Investigative Site
state: Pennsylvania
city: Nashville
country: United States
facility: Investigative Site
state: Tennessee
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Daniel Cho, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Journal of Clinical Oncology, 2009 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 27, No 15S (May 20 Supplement), 2009: 5101