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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Colon Cancer	Drug: Perifosine; Drug: Capecitabine; Other: Perifosine Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 381 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Randomized Placebo-Controlled Study of Perifosine in Combination With Single Agent Chemotherapy for Metastatic Cancer Patients
• Study Start Date: August 2005
• Actual Primary Completion Date: December 2010
• Actual Study Completion Date: October 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

  Show 49 Study Locations

Sponsors and Collaborators

AEterna Zentaris

Investigators

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

More Information

Publications of Results:

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.

• Responsible Party: AEterna Zentaris
• ClinicalTrials.gov Identifier: NCT00398879 History of Changes
• Other Study ID Numbers: Perifosine 211
• First Posted: November 14, 2006
• Last Update Posted: March 14, 2018
• Last Verified: February 2012

Keywords provided by AEterna Zentaris:

Capecitabine

Additional relevant MeSH terms:

Neoplasm Metastasis; Neoplasms; Neoplastic Processes; Pathologic Processes; Capecitabine; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents