Phase I Trial of Docetaxel With Perifosine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00399087
Recruitment Status : Completed
First Posted : November 14, 2006
Last Update Posted : February 13, 2014
Information provided by (Responsible Party):
AEterna Zentaris

Brief Summary:
This is a study of the drug perifosine given in combination with docetaxel. Perifosine is an oral anti-cancer agent that has been used in more than 140 people. Docetaxel is a standard chemotherapy agent used in many types of cancer. This study is designed to determine the highest dose of perifosine that can be administered to people every day while they are receiving docetaxel with or without a steroid called prednisone, without severe or prolonged nausea, vomiting and diarrhea. This study starts with patients taking 50 mg/day and goes up to 150 mg/day.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: Perifosine Drug: Docetaxel Drug: Prednisone Phase 1

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 39 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Trial of the Combination of Perifosine and Docetaxel With or Without Prednisone
Study Start Date : November 2004
Actual Primary Completion Date : January 2010
Actual Study Completion Date : January 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Steroids
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Perifosine D1 + Docetaxel Drug: Perifosine
Perifosine oral administration
Drug: Docetaxel
IV administration
Experimental: Perifosine D1+ Docexatel+Prednisone Drug: Perifosine
Perifosine oral administration
Drug: Docetaxel
IV administration
Drug: Prednisone
Oral administration
Experimental: Perifosine+ D1,8 and 15+Docetaxel+Prednisone Drug: Perifosine
Perifosine oral administration
Drug: Docetaxel
IV administration
Drug: Prednisone
Oral administration

Primary Outcome Measures :
  1. Safety [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. Disease progression [ Time Frame: 3 years ]

Information from the National Library of Medicine

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

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00399087

United States, Tennessee
Investigative Site
Johnson City, Tennessee, United States, 37604
Sponsors and Collaborators
AEterna Zentaris

Publications of Results:
Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 24, No 18S (June 20 Supplement), 2006: 13066

Responsible Party: AEterna Zentaris Identifier: NCT00399087     History of Changes
Other Study ID Numbers: Perifosine 105
First Posted: November 14, 2006    Key Record Dates
Last Update Posted: February 13, 2014
Last Verified: February 2013

Additional relevant MeSH terms:
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal