Sulindac and Tamoxifen in Treating Patients With Desmoid Tumor

Children's Oncology Group

Status and phase: Completed; Phase 2

Conditions: Desmoid Tumor

Treatments: Other: laboratory biomarker analysis; Drug: sulindac; Drug: tamoxifen citrate

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00068419

CDR0000322260 (Other Identifier)

U10CA098543 (U.S. NIH Grant/Contract)

COG-ARST0321 (Other Identifier)

ARST0321

NCI-2009-00424 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 70 patients

Sex: All

Ages: Under 18 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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70 participants in 1 patient group

Treatment (enzyme inhibitor therapy, anti-estrogen therapy)

Experimental group

Description:

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:

Drug: tamoxifen citrate

Drug: sulindac

Other: laboratory biomarker analysis