Sulindac and Tamoxifen in Treating Patients With Desmoid Tumor

NCT ID: NCT00068419

Last Updated: 2020-02-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-02-29
• Study Completion Date: 2010-04-26

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.

Conditions

Desmoid Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (enzyme inhibitor therapy, anti-estrogen therapy)

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.

Group Type: EXPERIMENTAL

tamoxifen citrate

Intervention Type: DRUG

Given orally

sulindac

Intervention Type: DRUG

Given orally

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

tamoxifen citrate

Given orally

Intervention Type: DRUG

sulindac

Given orally

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

Nolvadex; TAM; tamoxifen; TMX; Aflodac; Algocetil; Clinoril; SULIN

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

• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Children's Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen Skapek, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

Children's Oncology Group

Monrovia, California, United States

Countries

United States

Other Identifiers

NCI-2009-00424

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000322260

Identifier Type: OTHER

Identifier Source: secondary_id

COG-ARST0321

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ARST0321

Identifier Type: -

Identifier Source: org_study_id