A Phase 1 Trial of the Combination of Perifosine and Docetaxel With or Without Prednisone
18 Years
N/A
Both
Neoplasms
Trial Information
A Phase 1 Trial of the Combination of Perifosine and Docetaxel With or Without Prednisone
This is a phase 1, open-label trial of perifosine and docetaxel with or without prednisone
in patients with malignancies for whom single agent docetaxel is a reasonable treatment
option. All patients will receive docetaxel at a dose of 75 mg/m2 on day 8 of a 21-day cycle
either without (Arm A) or with prednisone 5 mg bid on days 1 - 21 (Arms B and C). (Patients
on all arms will receive premedication with dexamethasone around the time of docetaxel
administration either as described in the product insert for arm A or as used in prior
prostate cancer phase III studies for arm B and C. The 1st cohort of patients on Arm A and
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. Alternating cohorts of 3 patients will be entered
first to Arm A and then to Arm B. At the completion of arms A and B, 3 cohorts of patients
will be entered who will receive perifosine weekly at doses of 900, 1200 and 1500 mg. The
total dose will be divided into 300 mg doses which will be delivered at least 4 hours apart.
The perifosine dose escalation for each arm 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
Inclusion Criteria
- Patients must have histologically or cytologically confirmed diagnosis of cancer for
which treatment with single agent docetaxel would be an appropriate treatment option.
- At least 18 years of age.
- Patients may be currently receiving docetaxel using the schedule in the protocol, as
long as the treating investigator has reasonable expectation that the patient will
continue to receive docetaxel 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 in the protocol:
leukocytes >=4,000/microL, absolute neutrophil count >=1,500/microL, platelets
>=100,000/microL, HCT > 28%, total bilirubin < 1.5 x upper limit of normal, AST
(SGOT)/ALT (SGPT) <=2.5 X institutional upper limit of normal, creatinine <= 2.5
mg/dl
- 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
Polysorbate 80 (Tween 80).
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Safety
Outcome Time Frame:
3 years
Safety Issue:
No
Authority:
United States: Food and Drug Administration
Study ID:
Perifosine 105
NCT ID:
NCT00399087
Start Date:
November 2004
Completion Date:
January 2011
Related Keywords:
- Neoplasms
- Neoplasms
Name | Location |
|---|---|
| Investigative Site | Johnson City, Tennessee 37604 |
