Placebo-Controlled Study of Perifosine + Single Agent Chemotherapy for Metastatic Cancer Patients

• ClinicalTrials.gov Identifier: NCT00398879
• Recruitment Status: Completed
• First Posted: November 14, 2006
• Last Update Posted: March 14, 2018
• Sponsor: AEterna Zentaris
• Information provided by (Responsible Party): AEterna Zentaris

Tracking Information

• First Submitted Date: November 6, 2006
• First Posted Date: November 14, 2006
• Last Update Posted Date: March 14, 2018
• Study Start Date: August 2005
• Actual Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 12, 2018)

Effects of perifosine on time to progression [ Time Frame: Every 12 weeks ]

Time to progression will be measured from the first day of study drug until progression.

• Original Primary Outcome Measures (submitted: November 10, 2006): To determine the proportion of patients progression free at 6 months.

Current Secondary Outcome Measures (submitted: March 12, 2018)

• Toxicity [ Time Frame: Every 12 weeks ]
  Determination of the toxicity of single agent chemotherapy in combination with perifosine. Toxicity evaluation is to be performed throughout the study.
• Comparison of time to progression to historical experience [ Time Frame: Every 12 weeks ]
  To compare the time to progression of chemotherapy in combination with placebo to historical experience.

Original Secondary Outcome Measures (submitted: November 10, 2006)

• 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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Condition: Colon Cancer

Intervention

• Drug: Perifosine
  Perifosine 50 mg/d qd
  Other Names:

  • D-21266
  • KRX-0401
• Drug: Capecitabine
  Capecitabine 825 mg/m^2 BID days 1 - 14 q 3 weeks
• Other: Perifosine Placebo
  Placebo to Perifosine 50 mg/d qd
  Other Name: placebo

Study Arms

• Experimental: Arm 1: Perifosine + Capecitabine
  Perifosine 50 mg/d qd + Capecitabine 825 mg/m^2 BID days 1 - 14 q 3 weeks until progression
  Interventions:

  • Drug: Perifosine
  • Drug: Capecitabine
• Placebo Comparator: Arm 2: Perifosine Placebo + Capecitabine
  Perifosine Placebo 50 mg/d qd + Capecitabine 825 mg/m^2 BID days 1 - 14 q 3 weeks until progression
  Interventions:

  • Drug: Capecitabine
  • Other: Perifosine Placebo

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 10, 2011): 381
• Original Enrollment (submitted: November 10, 2006): 100
• Actual Study Completion Date: October 2011
• Actual Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00398879
• Other Study ID Numbers: Perifosine 211
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: AEterna Zentaris
• Study Sponsor: AEterna Zentaris
• Collaborators: Not Provided

Investigators

• Study Chair: Craig Henderson, MD; Online Collaborative Oncology Group

• PRS Account: AEterna Zentaris
• Verification Date: February 2012