Sulindac and Tamoxifen in Treating Patients With Desmoid Tumor

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Desmoid Tumor

Intervention / Treatment
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* Drug: tamoxifen citrate
* Drug: sulindac
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (enzyme inhibitor therapy, anti-estrogen therapy)<br>Patients receive oral sulindac and oral tamoxifen citrate 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. | Drug: tamoxifen citrate<br>* Given orally<br>* Other names: TMX;Drug: sulindac<br>* Given orally<br>* Other names: SULIN;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Failure Free at 2 Years Following Study Entry | Kaplan Meier estimate of failure free survival at 2 years, where failure free survival is defined as the time to relapse, progression, second malignancy, and death whichever occurs first. | Up to 2 years | 
| Percentage of Patients Experiencing a Grade 3 or Higher Adverse Event During Therapy. | The percentage of patients experiencing a grade 3 or higher adverse event as assessed by the National Cancer Institute Common Toxicity Terminology for Adverse Events v3.0 | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Tumor Response From Imaging | Percentage of patients with a tumor response where tumor response is assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) | Baseline up to 5 years | 
| Mean Change in Response Measured by MRI | The mean change in response measured by MRI. Response is assessed by the lesion size which is derived from the sum of the longest of the three orthogonal diameters (from MRI) of each target lesion. | From baseline to up to 5 years | 
| Percentage of Patients Failure Free at 2 Years by Pathological Response | The failure free survival is compared by the log-rank test between patient subgroups defined by pathological response of cyclooxygenase-2 (COX-2) and estrogen/progesterone receptor expression | From enrollment to up to 2 years | 
| Percentage of Patients Experiencing Short-term Endocrine Toxicity | The percentage of patients experiencing short-term endocrine toxicity between treatment groups is compared using the chi-square test | At study entry |