Clinical trial NCT00398879: Placebo-Controlled Study of Perifosine + Single Agent Chemotherapy for Metastatic Cancer Patients
Official title: A Randomized Placebo-Controlled Study of Perifosine in Combination With Single Agent Chemotherapy for Metastatic Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colon Cancer
Keywords: Capecitabine
Lead sponsor: AEterna Zentaris
Sponsor class: INDUSTRY
First posted: 2006-11-14
Enrollment: 381
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an exploratory phase 2, randomized placebo-controlled trial with stratification for disease and chemotherapy type. The study is subsequently closed to enrollment in all arms except patients with metastatic colorectal cancer which would be randomized to either capecitabine plus perifosine or capecitabine alone.

The effects of perifosine may be manifested by increased time to progression, tumor regression reflected in partial or complete responses, or a combination of these outcomes. The primary goal of this trial is to obtain a preliminary and objective assessment of the effects of perifosine on time to progression.

Detailed description: This is an exploratory phase 2, randomized placebo-controlled trial with stratification for disease and chemotherapy type. If there is any evidence of improved time to progression in any tumor type with any of the drugs to be evaluated, the initial study or component(s) of the study will be expanded to increase the certainty that this is an effect of perifosine. If there is compelling evidence of benefit from this study, a phase 3 trial will be conducted to obtain proof of principle.

Primary Study Objectives:

To determine the time to tumor progression when receiving single agent chemotherapy (capecitabine) in combination with perifosine in comparison to patients receiving single agent chemotherapy (capecitabine) alone (i.e., with placebo).

Secondary Study Objectives:

* To determine the toxicity of single agent chemotherapy in combination with perifosine.
* To compare the time to progression of chemotherapy in combination with placebo to historical experience.
* Overall survival will also be evaluated.

Eligibility criteria: Inclusion Criteria:

1. In the opinion of the treating physician, treatment with one of the following regimens should represent an appropriate treatment for the patient.

   - Capecitabine 825 mg/m2 BID days 1 - 14 q 3 weeks
2. Patients should have a histologically or cytologically confirmed diagnosis of colorectal cancer.
3. Patients must have received at least one but no more than two prior chemotherapy regimen(s) for the treatment of metastatic or recurrent disease.
4. ECOG performance status 0 or 1.

   * Leukocytes \>= 4,000/μL
   * absolute neutrophil count \>= 1,500/ μL
   * platelets \>= 100,000/ μL
   * HCT \> 28% (with or without growth factor support)
   * Creatinine \<= 2.5 mg/dl
   * total bilirubin \< 1.5 x upper limit of normal
   * transaminase \< 2.5 x upper limit of normal
5. Patients must have recovered from acute toxicity-excluding alopecia-related to prior therapy, including surgery or radiotherapy.
6. Patients with brain metastases may be admitted, provided the disease has been treated and been stable for 2 months.
7. Patients must have ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Patients receiving any other investigational agents or devices.
2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to perifosine (miltefosine or edelfosine).
3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, psychiatric illness, or social situations that would limit compliance with study requirements.
4. HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study due to potential pharmacokinetic interactions with perifosine.
5. Patients with a history of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment), or New York Heart Assoc. class II - IV congestive heart failure.
6. Female patients who are pregnant or lactating are ineligible.

Primary outcomes:
measure: Effects of perifosine on time to progression
timeFrame: Every 12 weeks
Secondary outcomes:
measure: Toxicity
timeFrame: Every 12 weeks
measure: Comparison of time to progression to historical experience
timeFrame: Every 12 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Arizona
city: Beverly Hills
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: California
city: Deer Park
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: California
city: Monterey
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: California
city: Newport Beach
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: California
city: Pomona
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: California
city: Santa Rosa
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: California
city: Soquel
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: California
city: Stockton
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: California
city: Colorado Springs
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Colorado
city: Greeley
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Colorado
city: Middletown
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Connecticut
city: Norwich
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Connecticut
city: Aventura
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Florida
city: Coral Springs
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Florida
city: Lake City
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Florida
city: Miami
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Florida
city: Ormond Beach
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Florida
city: Sebastian
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Florida
city: Vero Beach
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Florida
city: Augusta
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Georgia
city: Lawrenceville
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Georgia
city: Marietta
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Georgia
city: Galesburg
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Illinois
city: Park Ridge
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Illinois
city: Louisville
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Kentucky
city: Lafayette
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Louisiana
city: Grand Rapids
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Michigan
city: Kalamazoo
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Michigan
city: Branson
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Missouri
city: Billings
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Montana
city: Great Falls
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Montana
city: Albany
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: New York
city: Armonk
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: New York
city: Great Neck
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: New York
city: Wilmington
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: North Carolina
city: Dayton
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Ohio
city: Pottsville
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Pennsylvania
city: Sayre
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Pennsylvania
city: Greenville
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: South Carolina
city: Chattanooga
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Tennessee
city: Memphis
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Tennessee
city: Dallas
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Texas
city: Dallas
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Texas
city: Tyler
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Texas
city: Chesapeake
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Virginia
city: Norfolk
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Virginia
city: Spokane
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Washington
city: Appleton
country: United States
facility: AOI Pharmaceuticals Investigative Site
state: Wisconsin
Study officials:
affiliation: Online Collaborative Oncology Group
name: Craig Henderson, MD
role: STUDY_CHAIR
References:
citation: Bendell JC, Nemunaitis J, Vukelja SJ, Hagenstad C, Campos LT, Hermann RC, Sportelli P, Gardner L, Richards DA. Randomized placebo-controlled phase II trial of perifosine plus capecitabine as second- or third-line therapy in patients with metastatic colorectal cancer. J Clin Oncol. 2011 Nov 20;29(33):4394-400. doi: 10.1200/JCO.2011.36.1980. Epub 2011 Oct 3.