A Phase 1 Trial of the Combination of Perifosine and Paclitaxel Given Either Weekly or Every 3 Weeks
18 Years
N/A
Both
Neoplasms
Trial Information
A Phase 1 Trial of the Combination of Perifosine and Paclitaxel Given Either Weekly or Every 3 Weeks
This is a phase 1, open-label trial of perifosine and paclitaxel administered either weekly
or every 3 weeks in patients with malignancies for whom single agent paclitaxel is a
reasonable treatment option. All patients will receive paclitaxel either at a dose of 80
mg/m2 on days 1, 8 and 15 of a 28-day cycle (Arm A) or at 175 mg/m2 administered on day 8 of
a 21 day cycle (Arm B). Patients on both arm A and arm B will receive premedication with
diphenhydramine 50 mg IV 30 minutes prior to treatment; ranitidine 50 mg IV 30 minutes prior
to treatment and dexamethasone 20 mg IV at 30 minutes prior to treatment. The 1st cohort of
patients on Arm A will receive perifosine orally at a dose of 50 mg per day for the first 21
days of the 28-day cycle and on Arm B will receive perifosine orally at a dose of 50 mg per
day for the first 14 days of the 21-day cycle. On each arm, the perifosine dose will be
escalated in subsequent groups to 50 mg bid and then 50 mg tid as tolerated. (See below)
Alternating cohorts of 3 patients will be entered first to Arm A and then to Arm B. The
perifosine dose escalation for Arm A and Arm B will be performed separately according to the
following algorithm. For each arm, a maximum tolerated dose (MTD) will be defined as a dose
that can be given without grade 3/4 non-hematologic toxicity in more than 1/3 patients. If
2/3 patients in any cohort encounter a grade 3/4 non-hematologic toxicity, an additional 3
patients will be added. If the dose is intolerable for >3/6 patients then the previous dose
level will be declared the MTD for that arm.
Inclusion Criteria:
- Histologically or cytologically confirmed diagnosis of cancer for which treatment
with single agent paclitaxel would be an appropriate treatment option.
- At least 18 years of age.
- Patients can have received no more than two prior chemotherapy regimens for
metastatic disease. Patients may be currently receiving paclitaxel using one of the
schedules in the protocol, as long as the treating investigator has reasonable
expectation that the patient will continue to receive paclitaxel for 2 or more
additional cycles. The current regimen does not count towards the 2 regimens as long
as the patient is not progressing on therapy.
- Patients must have a life expectancy of more than 3 months.
- Patients must have a performance status of 0 to 2 according to the ECOG criteria.
- Patients must have normal organ and marrow function as defined below: leukocytes >=
4,000/microL, absolute neutrophil count >= 1,500/microL, platelets >= 100,000/microL,
HCT > 28%, total bilirubin < 2 x upper limit of normal, AST (SGOT)/ALT (SGPT) <= 2.5
X institutional upper limit of normal, creatinine <= 2.5 mg/dl transaminase < 2.5
times institution's upper normal limits
- Patients must have recovered from acute toxicity related to prior therapy, excluding
alopecia, including surgery or radiotherapy.
- Patients must be able to ingest oral medications.
- Female patients who are pregnant or lactating are ineligible. All females of
childbearing potential must have a negative serum pregnancy test within 72 hours of
treatment. Men and women of childbearing potential must agree to employ adequate
contraception to prevent pregnancy while on therapy and for four weeks after the
completion of treatment.
- Patients must have ability to understand and the willingness to sign a written
informed consent document.
Exclusion Criteria:
- Patients may not be 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).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection and psychiatric illness/social situations that would limit compliance with
study requirements.
- HIV-positive patients receiving combination anti-retroviral therapy are excluded from
the study because of possible pharmacokinetic interactions with perifosine.
- 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.
- Patients with a history of hypersensitivity reaction to products containing a
Chremophor EL.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
GI Toxicities
Outcome Time Frame:
3 months
Safety Issue:
Yes
Authority:
United States: Food and Drug Administration
Study ID:
Perifosine 104
NCT ID:
NCT00399126
Start Date:
November 2004
Completion Date:
October 2011
Related Keywords:
- Neoplasms
- Neoplasms
Name | Location |
|---|---|
| AOI Pharmaceuticals Investigative Site | Chattanooga, Tennessee 37404 |
