A Trial of Perifosine in Patients With Chemo-Insensitive Sarcomas

Sarcoma Alliance for Research Through Collaboration (SARC) Multicenter Trial: A Phase II Trial of Perifosine in Patients With Chemo-Insensitive Sarcomas

This is a phase II study of perifosine in patients with chondrosarcomas, alveolar soft part sarcomas and extra-skeletal myxoid chondrosarcomas. Patients will receive perifosine 100 mg orally qhs with food until disease progression. The goals of this study include:

• In this study a daily dose of perifosine previously determined to be relatively non-toxic will be evaluated in patients with chondrosarcomas, alveolar soft part sarcomas and extra-skeletal myxoid chondrosarcomas.
• Response to therapy will be based on regression of measurable disease according to Choi criteria. Time to progression and duration of stable disease will be measured as secondary endpoints of the study.

Study Overview

• Status: Completed
• Conditions: Chondrosarcomas; Alveolar Soft Part Sarcomas; Extra Skeletal Myxoid Chondrosarcomas
• Intervention / Treatment: Drug: Perifosine; Other: Loperamide; Other: Allopurinol; Other: Antiemetics

Detailed Description

This is a phase II study of perifosine in patients with chondrosarcomas, alveolar soft part sarcomas and extra-skeletal myxoid chondrosarcomas. Patients will receive perifosine 100 mg orally qhs with food until disease progression.

Perifosine is available in 50 mg tablets. Patients will take two perifosine 50 mg tablets orally once a day at bedtime with food. Administering the drug qhs has been shown to decrease gastrointestinal toxicity in some patients. Patients may need anti-emetics and/or anti-diarrheals. All patients may continue therapy unless disease progression is documented on two occasions at least 4 weeks apart. Patients who experience toxicity may continue on treatment with doses delayed or reduced. Evaluation of all lesions for progression or response will be made at 3-month intervals.

STUDY KEY POINTS

• Treatment will be administered on an outpatient basis in 28-day cycles.
• Growth factors should not be needed, however, use by patients on this trial is NOT prohibited.
• A favorable outcome will be defined as a complete or partial response according to the Choi criteria or stable disease by the Choi criteria for 6 months or longer.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed diagnosis of chondrosarcoma, extra-skeletal myxoid chondrosarcoma or alveolar soft part sarcoma.
• Patients may have had prior chemotherapy, but if the patient has had three or more forms of prior chemotherapy for metastases, the patient's clinical course should be discussed with the study chairman before the patient is enrolled on study
• Patients must have progression of disease by Choi criteria.
• ECOG performance status 0-1. Patients with ECOG PS of 2 may be admitted with approval from the study chairman.
• At least 13 years of age.
• Patients must have measurable disease.
• Patients who have brain metastases that have not progressed for at least 2 months following surgery or radiotherapy will be considered after discussion with the study chairman.
• Patients must have a life expectancy of more than 3 months.

• Patients must have normal organ and marrow function, unless in the opinion of the treating investigator, the abnormality is related to tumor, and the study chairman agree the abnormality is unlikely to affect the safety of perifosine use. Normal organ and marrow function is described below:

  • ANC >1.5 x 109 /L
  • Platelets >75,000/ mm3
  • HCT > 28% (with or without growth factor support)
  • Creatinine <= 2.5 mg/dl
  • Total bilirubin < 1.5 x upper limit of normal
  • Transaminase <= 2.5 x upper limit of normal
• Patients must have recovered from acute toxicity related to prior therapy, including surgery or radiotherapy to grade <= 1 (excluding alopecia) at the time of enrollment.
• Patients must be able to ingest oral medications or to obtain them through a gastrostomy tube.
• Female patients who are pregnant or lactating are ineligible. All females of childbearing potential must have a negative urine or 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 the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patients receiving investigational or commercial agents or therapies administered with the intent to treat the patient's malignancy, except bisphosphonates.
• 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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: chondrosarcoma; Patients with sarcoma subtype: histologically or cytologically confirmed diagnosis of chondrosarcoma. Supportive Care Guidelines for perifosine include antiemetic prophylaxis (antiemetics will be administered at the treating investigator's discretion), diarrhea management (loperamide), and hyperuricemia prophylaxis (allopurinol).	Drug: Perifosine; Perifosine is available in 50 mg tablets. Patients will take two perifosine 50 mg tablets orally once a day at bedtime with food.; Other Names: D-21266; KRX-0401; Other: Loperamide; All patients should be instructed to take loperamide at the earliest signs of diarrhea and/or abdominal cramping after beginning perifosine.; Other: Allopurinol; Patients with a known history of hyperuricemia and/or gout should receive prophylactic treatment with allopurinol 300 mg po daily.; Other: Antiemetics; Antiemetic prophylaxis will be administered at the treating investigator's discretion.
Experimental: Group B: alveolar soft part sarcoma; Patients with sarcoma subtype: histologically or cytologically confirmed diagnosis of alveolar soft part sarcoma. Supportive Care Guidelines for perifosine include antiemetic prophylaxis (antiemetics will be administered at the treating investigator's discretion), diarrhea management (loperamide), and hyperuricemia prophylaxis (allopurinol).	Drug: Perifosine; Perifosine is available in 50 mg tablets. Patients will take two perifosine 50 mg tablets orally once a day at bedtime with food.; Other Names: D-21266; KRX-0401; Other: Loperamide; All patients should be instructed to take loperamide at the earliest signs of diarrhea and/or abdominal cramping after beginning perifosine.; Other: Allopurinol; Patients with a known history of hyperuricemia and/or gout should receive prophylactic treatment with allopurinol 300 mg po daily.; Other: Antiemetics; Antiemetic prophylaxis will be administered at the treating investigator's discretion.
Experimental: Group C: extra-skeletal myxoid; Patients with sarcoma subtype: histologically or cytologically confirmed diagnosis of extra-skeletal myxoid chondrosarcoma. Supportive Care Guidelines for perifosine include antiemetic prophylaxis (antiemetics will be administered at the treating investigator's discretion), diarrhea management (loperamide), and hyperuricemia prophylaxis (allopurinol).	Drug: Perifosine; Perifosine is available in 50 mg tablets. Patients will take two perifosine 50 mg tablets orally once a day at bedtime with food.; Other Names: D-21266; KRX-0401; Other: Loperamide; All patients should be instructed to take loperamide at the earliest signs of diarrhea and/or abdominal cramping after beginning perifosine.; Other: Allopurinol; Patients with a known history of hyperuricemia and/or gout should receive prophylactic treatment with allopurinol 300 mg po daily.; Other: Antiemetics; Antiemetic prophylaxis will be administered at the treating investigator's discretion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	To investigate whether perifosine has a response rate of > 20% in this group of patients with chemo-insensitive sarcomas.	>= 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best overall response	Best response recorded from the start of the treatment until disease progression/recurrence.	>= 6 months
Stable disease of six months or greater	Stable disease is measured from the start of treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started.	>= 6 months

Collaborators and Investigators

• Sponsor: AEterna Zentaris
• Collaborators: Sarcoma Alliance for Research through Collaboration
• Investigators: Study Chair: Dejka Araujo, MD, MD Anderson Cancer Center, Dept of Sarcoma

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: November 17, 2006
• First Submitted That Met QC Criteria: November 17, 2006
• First Posted (Estimate): November 20, 2006

Study Record Updates

• Last Update Posted (Actual): March 7, 2018
• Last Update Submitted That Met QC Criteria: March 6, 2018
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: Perifosine; Chemo Insensitive Sarcomas; Chondrosarcomas; Alveolar soft part sarcomas; Extra skeletal myxoid chondrosarcomas
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Sarcoma; Chondrosarcoma; Sarcoma, Alveolar Soft Part; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Gastrointestinal Agents; Protective Agents; Antioxidants; Free Radical Scavengers; Gout Suppressants; Allopurinol; Loperamide; Antidiarrheals; Antiemetics
• Other Study ID Numbers: Perifosine 214