Sulindac and Tamoxifen in Treating Patients With Desmoid Tumor

Phase 2

Completed

Conditions: Desmoid Tumor

Interventions: Drug: tamoxifen citrate
Drug: sulindac
Other: laboratory biomarker analysis

Registration Number: NCT00068419

Lead Sponsor: Children's Oncology Group

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 70

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (enzyme inhibitor therapy, anti-estrogen therapy)	tamoxifen citrate	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.
Treatment (enzyme inhibitor therapy, anti-estrogen therapy)	sulindac	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.
Treatment (enzyme inhibitor therapy, anti-estrogen therapy)	laboratory biomarker analysis	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Patients Failure Free at 2 Years Following Study Entry	Up to 2 years	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.
Percentage of Patients Experiencing a Grade 3 or Higher Adverse Event During Therapy.	Up to 12 months	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

Secondary Outcome Measures

Name	Time	Method
Percentage of Patients With Tumor Response From Imaging	Baseline up to 5 years	Percentage of patients with a tumor response where tumor response is assessed according to Response Evaluation Criteria in Solid Tumors (RECIST)
Mean Change in Response Measured by MRI	From baseline to up to 5 years	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.
Percentage of Patients Failure Free at 2 Years by Pathological Response	From enrollment to up to 2 years	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
Percentage of Patients Experiencing Short-term Endocrine Toxicity	At study entry	The percentage of patients experiencing short-term endocrine toxicity between treatment groups is compared using the chi-square test