Official Title: “A Phase II Study of Sulindac and Tamoxifen in Patients With Desmoid Tumors That Are Recurrent or Not Amenable to Standard Therapy”

RATIONALE: 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.

PURPOSE: This phase II trial is studying how well giving sulindac together with tamoxifen works in treating patients with desmoid tumor.

Study Type: Interventional

Study Design: Treatment, Open Label

Study Primary Completion Date: October 2009

OBJECTIVES:

Primary - Determine the progression-free survival of patients with desmoid tumor that is recurrent or not amenable to standard therapy treated with sulindac and tamoxifen. - Determine the safety and efficacy of this regimen, in terms of event-free survival, of these patients.

Secondary - Determine the tumor response rate in patients treated with this regimen. - Correlate changes in MRI signal features of the tumor with clinical outcome in patients treated with this regimen. - 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. - Collect information about clinical factors that make a tumor unresectable at diagnosis and resectable during the four courses of study treatment. - 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.

PROJECTED ACCRUAL: A total of 68 patients will be accrued for this study within 4.8 years.

Intervention(s) in this Clinical Trial

• Drug: sulindac
• Drug: tamoxifen citrate

Primary Measures

• Event-free survival
  • Safety Issue?: No

Secondary Measures

• Tumor response rate
  • Safety Issue?: No
• Changes in MRI signal features of tumor with clinical outcomes
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

• Age
• 18 and under at original diagnosis
• Performance status
• Karnofsky 50-100% (patients over age 16) OR
• Lansky 50-100% (patients age 16 and under)
• Life expectancy
• At least 8 weeks
• Hematopoietic
• 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
• Hepatic
• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• ALT less than 2.5 times ULN
• Renal
• 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]) OR
• Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
• Cardiovascular
• No prior deep venous thrombosis
• EKG normal
• Pulmonary
• Chest x-ray normal
• Gastrointestinal
• No prior significant gastrointestinal hemorrhage
• No prior peptic ulcer disease
• Other
• Not pregnant or nursing
• Fertile patients must use effective nonhormonal contraception
• No evidence of active graft-versus-host disease
• No allergy to aspirin

PRIOR CONCURRENT THERAPY:

• Biologic therapy
• 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
• Chemotherapy
• See Disease Characteristics
• More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
• No concurrent anticancer chemotherapy
• Endocrine therapy
• No prior estrogen antagonists for desmoid tumor
• No concurrent hormonal contraceptives
• No concurrent steroids except for nontumor indications (e.g., asthma or severe allergic reactions)
• Radiotherapy
• See Disease Characteristics
• Recovered from prior radiotherapy
• No concurrent adjuvant radiotherapy
• Surgery
• See Disease Characteristics
• Other
• No prior nonsteroidal anti-inflammatory drugs (NSAIDs) for desmoid tumor
• No concurrent NSAIDs for desmoid tumor
• Occasional NSAIDs for musculoskeletal or other pain are allowed
• No concurrent participation in another COG therapeutic study

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 18 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Children's Oncology Group

Overall Clinical Trial Officials and Contacts

Steve Skapek, MD Study Chair University of Chicago Comer Children's Hospital  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00068419

Study ID Number: CDR0000322260

ClinicalTrials.gov Identifier: NCT00068419

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database