Clinical trial NCT00068419: Sulindac and Tamoxifen in Treating Patients With Desmoid Tumor
Official title: A Phase II Study of Sulindac and Tamoxifen in Patients With Desmoid Tumors That Are Recurrent or Not Amenable to Standard Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Desmoid Tumor
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-09-11
Enrollment: 70
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial is studying how well giving sulindac together with tamoxifen works in treating patients with desmoid tumor. Sulindac may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Hormone therapy using tamoxifen may fight cancer by blocking the use of estrogen. Combining sulindac with tamoxifen may kill more cancer cells.

Detailed description: PRIMARY OBJECTIVES:

I. To estimate the safety and efficacy of sulindac and tamoxifen in patients with recurrent desmoid tumor (DT) and primary DT that is not readily amenable to surgery or radiation therapy.

SECONDARY OBJECTIVES:

I. Determine the tumor response rate in patients treated with this regimen.

II. Correlate changes in Magnetic Resonance Imaging (MRI) signal features of the tumor with clinical outcome in patients treated with this regimen.

III. Correlate pathological studies of cyclooxygenase-2 (COX-2) and estrogen/progesterone receptor expression in the tumor with clinical outcome in patients treated with this regimen.

IV. Collect information about clinical factors that make a tumor unresectable at diagnosis and resectable during the four courses of study treatment.

V. Determine whether short-term endocrine toxicity is associated with treatment with this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral sulindac and oral tamoxifen twice daily for up to 12 months (four 3-month courses) in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) receive 1 additional month of treatment beyond documentation of CR.

After completion of study treatment, patients are followed for 5 years.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed desmoid tumor, meeting 1 of the following criteria:

  * Newly diagnosed disease

    * Not previously treated
    * Not amenable to complete surgical resection and/or radiotherapy

      * If surgical resection was attempted, there must be gross residual disease measurable by MRI
  * Radiographically documented recurrent or progressive disease

    * No prior chemotherapy or radiotherapy for the present recurrence

      * Tumors that progressed on prior chemotherapy are allowed provided patients have not received chemotherapy for this recurrence
* Measurable disease by gadolinium-enhanced MRI
* No other fibroblastic lesions or fibromatoses

  * Lipofibromatosis or desmoplastic fibroma of the bone allowed
* Performance status - Karnofsky Score 50-100% (patients over age 16)
* Performance status - Lansky Score 50-100% (patients age 16 and under)
* At least 8 weeks
* Absolute neutrophil count at least 1,000/mm\^3
* Platelet count at least 100,000/mm\^3 (transfusion independent)
* Hemoglobin at least 10.0 g/dL (transfusion allowed)
* No hemophilia
* No von Willebrand disease
* No other clinically significant bleeding diathesis
* Bilirubin no greater than 1.5 times upper limit of normal (ULN)
* Alanine aminotransferase (ALT) less than 2.5 times ULN
* Creatinine adjusted according to age as follows:

  * No greater than 0.4 mg/dL (≤ 5 months)
  * No greater than 0.5 mg/dL (6 months -11 months)
  * No greater than 0.6 mg/dL (1 year-23 months)
  * No greater than 0.8 mg/dL (2 years-5 years)
  * No greater than 1.0 mg/dL (6 years-9 years)
  * No greater than 1.2 mg/dL (10 years-12 years)
  * No greater than 1.4 mg/dL (13 years and over \[female\])
  * No greater than 1.5 mg/dL (13 years to 15 years \[male\])
  * No greater than 1.7 mg/dL (16 years and over \[male\])
* Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
* No prior deep venous thrombosis
* Electrocardiogram (EKG) normal
* Chest x-ray normal
* No prior significant gastrointestinal hemorrhage
* No prior peptic ulcer disease
* Not pregnant or nursing
* Fertile patients must use effective nonhormonal contraception
* No evidence of active graft-versus-host disease
* No allergy to aspirin
* Recovered from prior immunotherapy
* At least 7 days since prior anticancer biologic agents
* At least 6 months since prior allogeneic stem cell transplantation
* More than 1 week since prior growth factors
* No concurrent immunomodulating agents
* No prior nonsteroidal anti-inflammatory drugs (NSAIDs) for desmoid tumor
* More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
* No concurrent anticancer chemotherapy
* No prior estrogen antagonists for desmoid tumor
* No concurrent hormonal contraceptives
* No concurrent steroids except for non tumor indications (e.g., asthma or severe allergic reactions)
* No concurrent NSAIDs for desmoid tumor

  * Occasional NSAIDs for musculoskeletal or other pain are allowed
* Recovered from prior radiotherapy
* No concurrent adjuvant radiotherapy
* No concurrent participation in another COG therapeutic study

Primary outcomes:
measure: Percentage of Patients Failure Free at 2 Years Following Study Entry
timeFrame: Up to 2 years
measure: Percentage of Patients Experiencing a Grade 3 or Higher Adverse Event During Therapy.
timeFrame: Up to 12 months
Secondary outcomes:
measure: Percentage of Patients With Tumor Response From Imaging
timeFrame: Baseline up to 5 years
measure: Mean Change in Response Measured by MRI
timeFrame: From baseline to up to 5 years
measure: Percentage of Patients Failure Free at 2 Years by Pathological Response
timeFrame: From enrollment to up to 2 years
measure: Percentage of Patients Experiencing Short-term Endocrine Toxicity
timeFrame: At study entry
Other outcomes:
Locations:
city: Monrovia
country: United States
facility: Children's Oncology Group
state: California
Study officials:
affiliation: Children's Oncology Group
name: Stephen Skapek, MD
role: PRINCIPAL_INVESTIGATOR
References: