Sulindac and Tamoxifen in Treating Patients With Desmoid Tumor

• ClinicalTrials.gov Identifier: NCT00068419
• Recruitment Status: Completed
• First Posted: September 11, 2003
• Results First Posted: December 4, 2013
• Last Update Posted: February 19, 2020
• Sponsor: Children's Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Children's Oncology Group

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Desmoid Tumor	Drug: tamoxifen citrate; Drug: sulindac; Other: laboratory biomarker analysis	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 70 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Sulindac and Tamoxifen in Patients With Desmoid Tumors That Are Recurrent or Not Amenable to Standard Therapy
• Study Start Date: February 2004
• Actual Primary Completion Date: April 26, 2010
• Actual Study Completion Date: April 26, 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: tamoxifen citrate; Given orally; Other Names: Nolvadex; TAM; tamoxifen; TMX; Drug: sulindac; Given orally; Other Names: Aflodac; Algocetil; Clinoril; SULIN; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures :

1. Percentage of Patients Failure Free at 2 Years Following Study Entry [ Time Frame: 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.
2. Percentage of Patients Experiencing a Grade 3 or Higher Adverse Event During Therapy. [ Time Frame: 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 :

1. Percentage of Patients With Tumor Response From Imaging [ Time Frame: 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)
2. Mean Change in Response Measured by MRI [ Time Frame: 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.
3. Percentage of Patients Failure Free at 2 Years by Pathological Response [ Time Frame: 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
4. Percentage of Patients Experiencing Short-term Endocrine Toxicity [ Time Frame: At study entry ]
   The percentage of patients experiencing short-term endocrine toxicity between treatment groups is compared using the chi-square test

Eligibility Criteria

• Ages Eligible for Study: up to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

Children's Oncology Group

Monrovia, California, United States, 91016

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Stephen Skapek, MD; Children's Oncology Group

More Information

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT00068419
• Other Study ID Numbers: ARST0321; NCI-2009-00424 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); CDR0000322260 ( Other Identifier: PDQ (Physician Data Query) ); COG-ARST0321 ( Other Identifier: Children's Oncology Group ); U10CA098543 ( U.S. NIH Grant/Contract )
• First Posted: September 11, 2003
• Results First Posted: December 4, 2013
• Last Update Posted: February 19, 2020
• Last Verified: February 2019

Additional relevant MeSH terms:

Fibromatosis, Aggressive; Fibroma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Tamoxifen; Sulindac; Molecular Mechanisms of Pharmacological Action; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Bone Density Conservation Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Enzyme Inhibitors