Study of Perifosine + Capecitabine for Colon Cancer Patients

Study Overview
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Brief Summary
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This is a Phase I study of Perifosine + Capecitabine for patients with advanced colon cancer.

Detailed Description
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This study is a Phase I trial. A total of 3 - 9 patients will be enrolled. Three patients will initially be enrolled. There will be no dose escalation in this study as only one dose for perifosine (50 mg) in combination with one dose of capecitabine (1000 mg/m2 BID) will be evaluated. The maximum tolerated dose (MTD) is defined in which fewer than 33% of patients experienced DLT attributable to the study drug(s), when at least six patients have been treated at that dose and are evaluable for toxicity. Pharmacokinetic (PK) data will also be evaluated from all enrolled patients.

Official Title
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A Phase I Study of Perifosine + Capecitabine for Patients With Advanced Colon Cancer

Conditions
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Colon Cancer

Intervention / Treatment
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* Drug: Perifosine
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with 3rd line or > metastatic colon cancer Patients must have received or not be candidates for regimens containing 5- FU, oxaliplatin, irinotecan, bevacizumab, and cetuximab or panitumumab No prior exposure to perifosine Adequate bone marrow, liver, and renal function Patients must have at least one measurable lesion Patients must agree to have extra blood drawn for PK analyses Exclusion Criteria: Patients with prior exposure to perifosine. Patients receiving any other investigational agents or devices. History of allergic reactions attributed to compounds of similar chemical or biologic composition to perifosine (miltefosine or edelfosine). Patients with known dipyrimidine dehydrogenase (DPD) deficiency or prior severe reaction to 5-FU. Patients with known central nervous system CNS metastases. Patients with known HIV, Hepatitis B, or Hepatitis C seropositivity. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection and psychiatric illness/social situations that would limit compliance with study requirements. Patients with a history of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment), or New York Heart Association class II-IV congestive heart failure. Female patients who are pregnant or lactating are ineligible.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Perifosine +Capecitabine<br>One cycle of therapy will be defined as 3 weeks (21 days). Perifosine 50 mg qd (Days 1-21) + Capecitabine 1000 mg/m2 BID (Days 1-14). | Drug: Perifosine<br>* Perifosine 50 mg orally once a day (Days 1-21)<br>* Other names: KRX-0401;Drug: Capecitabine<br>* Capecitabine 1000 mg/m2 orally twice per day (Days 1-14)<br>* Other names: Xeloda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of the combination of perifosine and capecitabine (i.e., dose limiting toxicity) | The maximum tolerated dose (MTD) is defined in which fewer than 33% of patients experienced dose limiting toxicity (DLT) attributable to the study drug(s), when at least six patients were treated at that dose and are evaluable for toxicity. A DLT will be defined as any of the following deemed to be related to study drug(s): Grade 3 non-hematologic toxicity except alopecia not reversible to Grade 2 or less within 96 hours Any Grade 4 toxicity DLT will be based on the first cycle of treatment (first 21 days). Toxicity will be graded according to the NCI CTCAE version 3.0. To be evaluable for toxicity, a patient must receive at least 1 complete course of treatment or have experienced DLT. | Every 3 weeks after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best overall response | The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response Evaluation Criteria in solid tumors (RECIST): Measurable disease is defined as the presence of at least one measurable lesion. Measurable lesions are lesions that can be accurately measured in at least one dimension and fit one of the following criteria: Longest diameter ≥ 20 mm using conventional techniques, or ≥ 10 mm with spiral CT scan. | Every 3 cycles after dosing (length of one cycle is 21 days) | 
| Time to progression | This is the interval from the initiation of treatment to the time of documented, objective progression using the same methods of evaluation that were used at baseline. In order for a patient to be regarded as having progressive disease, the following criteria must be met: The site of disease must have been evaluated either at baseline or while receiving study medication. Both evaluations must use the same methodology. PET scan results will not be used as evidence of either progression or response.. | Every 3 cycles after dosing (length of one cycle is 21 days) | 
| Pharmacokinetic (PK) data for the combination of perifosine and capecitabine | PK data will also be evaluated from all enrolled patients. PK analyses will present peak plasma concentrations (Cmax) as well as Area under the plasma concentration verus time curve (AUC). | Up to cyle 5 no pharmacokinetic samples were obtained. Cycle 1/Day 11 until Cycle 4/Day 11: pharmacokinetic samples obtained 0.5, 1, 2, 4, 6 and 8 hours after dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Perifosine, Capecitabine, Colon Cancer