Clinical trial NCT00053794: Perifosine in Treating Patients With Metastatic or Locally Advanced Soft Tissue Sarcoma
Official title: A Phase II Study Of Perifosine (D-21266) In Patients With Previously Untreated Metastatic Or Locally Advanced Soft Tissue Sarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Endometrial Cancer
Sarcoma
Keywords: adult alveolar soft-part sarcoma
adult angiosarcoma
adult fibrosarcoma
adult leiomyosarcoma
adult liposarcoma
adult synovial sarcoma
endometrial stromal sarcoma
uterine leiomyosarcoma
adult malignant hemangiopericytoma
stage III adult soft tissue sarcoma
stage III uterine sarcoma
stage IV uterine sarcoma
recurrent adult soft tissue sarcoma
recurrent uterine sarcoma
adult malignant fibrous histiocytoma
adult neurofibrosarcoma
adult rhabdomyosarcoma
stage IV adult soft tissue sarcoma
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-02-06
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of perifosine in treating patients who have metastatic or locally advanced soft tissue sarcoma.

Detailed description: OBJECTIVES:

* Determine the efficacy of perifosine, in terms of response rate and duration of response, in patients with untreated metastatic or locally advanced soft tissue sarcoma.
* Determine the toxicity of this drug in these patients.
* Determine the early progression rate in patients treated with this drug.

OUTLINE: This is a non-randomized, non-blinded, multicenter study.

Patients receive a loading dose of oral perifosine twice on day 1 and then once daily on days 2-21 for the first course. For all subsequent courses, patients receive a loading dose of oral perifosine once on day 1 and then once daily on days 2-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed for 1 month. Patients with stable or responsive disease are followed every 3 months thereafter.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 12-18 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed metastatic or locally advanced soft tissue sarcoma that is incurable by standard therapies, including any of the following types:

  * Uterine sarcomas

    * Mixed mesodermal
    * Leiomyosarcoma
    * Endometrial stromal sarcoma
  * Alveolar soft part sarcoma
  * Angiosarcoma/lymphangiosarcoma
  * Fibrosarcoma
  * Hemangiopericytoma
  * Leiomyosarcoma
  * Liposarcoma
  * Malignant fibrous histiocytoma
  * Neurogenic sarcoma
  * Pleomorphic rhabdomyosarcoma
  * Synovial sarcoma
  * Unclassifiable sarcoma
  * Undifferentiated sarcoma
* Excluded diseases include the following:

  * Bone sarcomas (e.g., osteosarcoma, Ewing's sarcoma, chondrosarcoma)
  * Embryonal rhabdomyosarcoma
  * Carcinosarcoma
  * Kaposi's sarcoma
  * Malignant mesothelioma
  * Neuroblastoma
  * Gastrointestinal stromal tumor
* At least 1 unidimensionally measurable site of disease (outside the previously irradiated area) defined as:

  * At least 20 mm by x-ray or physical exam
  * At least 10 mm by spiral CT scan
  * At least 20 mm by non-spiral CT scan NOTE: Bone lesions are not considered measurable

NOTE: Patients whose sole site of disease is within a previously irradiated area are allowed if there is evidence of progression or new lesions in the irradiated field

* No known brain metastases

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* ECOG 0-2

Life expectancy

* At least 12 weeks

Hematopoietic

* Absolute granulocyte count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic

* Bilirubin no greater than upper limit of normal (ULN)
* AST no greater than 2.5 times ULN

Renal

* Creatinine no greater than ULN

Cardiovascular

* No symptomatic congestive heart failure
* No unstable angina pectoris
* No cardiac arrhythmia

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No prior allergic reactions attributed to compounds of similar chemical or biological composition to perifosine
* No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix
* No active or ongoing infection
* No psychiatric illness or social situation that would limit compliance with study requirements
* No other concurrent uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* No prior systemic chemotherapy for metastatic or locally advanced disease
* At least 6 months since prior adjuvant chemotherapy
* No other concurrent cytotoxic chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* See Disease Characteristics
* At least 4 weeks since prior radiotherapy (except low-dose, non-myelosuppressive radiotherapy)
* No concurrent radiotherapy to the sole site of measurable disease or for progressively symptomatic disease

Surgery

* At least 4 weeks since prior major surgery

Other

* No other concurrent anticancer therapy or investigational agents

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Center - Calgary
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency - Vancouver Island Cancer Centre
state: British Columbia
city: Hamilton
country: Canada
facility: Margaret and Charles Juravinski Cancer Centre
state: Ontario
city: London
country: Canada
facility: Cancer Care Ontario-London Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital - Toronto
state: Ontario
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
Study officials:
affiliation: Cancer Centre of Southeastern Ontario at Kingston General Hospital
name: Elizabeth A. Eisenhauer, MD
role: STUDY_CHAIR
References:
citation: Knowling M, Blackstein M, Tozer R, Bramwell V, Dancey J, Dore N, Matthews S, Eisenhauer E. A phase II study of perifosine (D-21226) in patients with previously untreated metastatic or locally advanced soft tissue sarcoma: A National Cancer Institute of Canada Clinical Trials Group trial. Invest New Drugs. 2006 Sep;24(5):435-9. doi: 10.1007/s10637-006-6406-7.