Study of Perifosine + Capecitabine for Colon Cancer Patients
Primary Purpose
Colon Cancer
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Perifosine
Capecitabine
Sponsored by
About this trial
This is an interventional treatment trial for Colon Cancer focused on measuring Perifosine, Capecitabine, Colon Cancer
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Perifosine +Capecitabine
Arm Description
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).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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..
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).
Full Information
NCT ID
NCT01048580
First Posted
January 9, 2010
Last Updated
June 26, 2018
Sponsor
AEterna Zentaris
Collaborators
SCRI Development Innovations, LLC
1. Study Identification
Unique Protocol Identification Number
NCT01048580
Brief Title
Study of Perifosine + Capecitabine for Colon Cancer Patients
Official Title
A Phase I Study of Perifosine + Capecitabine for Patients With Advanced Colon Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
November 2011
Overall Recruitment Status
Completed
Study Start Date
October 2009 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
October 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AEterna Zentaris
Collaborators
SCRI Development Innovations, LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a Phase I study of Perifosine + Capecitabine for patients with advanced colon cancer.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colon Cancer
Keywords
Perifosine, Capecitabine, Colon Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Perifosine +Capecitabine
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Perifosine
Other Intervention Name(s)
D-21266, KRX-0401
Intervention Description
Perifosine 50 mg orally once a day (Days 1-21)
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
Capecitabine 1000 mg/m2 orally twice per day (Days 1-14)
Primary Outcome Measure Information:
Title
Safety and tolerability of the combination of perifosine and capecitabine (i.e., dose limiting toxicity)
Description
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.
Time Frame
Every 3 weeks after dosing
Secondary Outcome Measure Information:
Title
Best overall response
Description
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.
Time Frame
Every 3 cycles after dosing (length of one cycle is 21 days)
Title
Time to progression
Description
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..
Time Frame
Every 3 cycles after dosing (length of one cycle is 21 days)
Title
Pharmacokinetic (PK) data for the combination of perifosine and capecitabine
Description
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).
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johanna Bendell,, MD
Organizational Affiliation
SCRI Development Innovations, LLC
Official's Role
Study Chair
12. IPD Sharing Statement
Citations:
Citation
Journal of Oncology, 2010 ASCO Annual Meeting Abstracts. Vol. 28, No. 15_suppl (May 20Supplement), 2010:e14086
Results Reference
result
Learn more about this trial
Study of Perifosine + Capecitabine for Colon Cancer Patients
We'll reach out to this number within 24 hrs