A Phase II Trial of Perifosine Following Tyrosine Kinase Inhibitor (TKI) - Failure in Patients With Renal Cancer

Renal Cell Carcinoma Clinical Trial

Official title:

A Phase II Trial of Perifosine Following Tyrosine Kinase Inhibitor Failure in Patients With Advanced Renal Cell Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00448721
• Other study ID #: Perifosine 228
• Status: Completed
• Phase: Phase 2
• First received: March 15, 2007
• Last updated: February 27, 2018
• Start date: March 2007
• Est. completion date: October 2011

Study information

• Verified date: February 2012
• Source: AEterna Zentaris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: October 2011
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 IFNa are allowed for adjuvant therapy or stage IV disease

• Patients may not have had prior mTOR inhibitors (CCI-779, RAD001)

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

Drug:
• Perifosine
Perifosine will be administered orally at 100mg PO daily with food.

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Investigative Site	Duarte	California
United States	Investigative Site	Nashville	Tennessee
United States	Investigative Site	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
AEterna Zentaris	Dana-Farber Cancer Institute

Country where clinical trial is conducted

United States, 

References & Publications (1)

Journal of Clinical Oncology, 2009 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 27, No 15S (May 20 Supplement), 2009: 5101

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To estimate the progression free survival	To estimate the progression free survival of Multi-Targeted Kinase Inhibitor (TKI) resistant patients with metastatic Renal Cell Carcinoma (RCC) who are treated with perifosine	Every 6 weeks
Secondary	To determine the objective response rate of perifosine	To determine the objective response rate of TKI resistant patients with metastatic RCC treated with perifosine.	Every 6 weeks
Secondary	To investigate the tolerability and toxicity	To investigate the tolerability and toxicity of perifosine in TKI resistant patients	Every 6 weeks
Secondary	To investigate surrogates of biologic target inhibition	To investigate surrogates of biologic target inhibition on PBMC's before and after therapy.	Every 6 weeks
Secondary	To collect pre-treatment tissue specimens	To collect pre-treatment tissue specimens and assess the pre-treatment activation status of the MAP-Kinase and PI3K-Akt pathways and correlate with clinical outcome.	Every 6 weeks
Secondary	To follow levels of pro-angiogenic cytokines	To follow levels of pro-angiogenic cytokines and surrogates of HIF activation before and during therapy.	Every 6 weeks