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Sulindac and Tamoxifen in Treating Patients With Desmoid Tumor

Primary Purpose

Desmoid Tumor

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
tamoxifen citrate
sulindac
laboratory biomarker analysis
Sponsored by
Children's Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Desmoid Tumor

Eligibility Criteria

undefined - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Oncology Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (enzyme inhibitor therapy, anti-estrogen therapy)

Arm 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.

Outcomes

Primary Outcome Measures

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.
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

Secondary Outcome Measures

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)
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.
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
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

Full Information

First Posted
September 10, 2003
Last Updated
February 7, 2020
Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00068419
Brief Title
Sulindac and Tamoxifen in Treating Patients With Desmoid Tumor
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 Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
February 2004 (undefined)
Primary Completion Date
April 26, 2010 (Actual)
Study Completion Date
April 26, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Desmoid Tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (enzyme inhibitor therapy, anti-estrogen therapy)
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
tamoxifen citrate
Other Intervention Name(s)
Nolvadex, TAM, tamoxifen, TMX
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
sulindac
Other Intervention Name(s)
Aflodac, Algocetil, Clinoril, SULIN
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Percentage of Patients Failure Free at 2 Years Following Study Entry
Description
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.
Time Frame
Up to 2 years
Title
Percentage of Patients Experiencing a Grade 3 or Higher Adverse Event During Therapy.
Description
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
Time Frame
Up to 12 months
Secondary Outcome Measure Information:
Title
Percentage of Patients With Tumor Response From Imaging
Description
Percentage of patients with a tumor response where tumor response is assessed according to Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame
Baseline up to 5 years
Title
Mean Change in Response Measured by MRI
Description
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.
Time Frame
From baseline to up to 5 years
Title
Percentage of Patients Failure Free at 2 Years by Pathological Response
Description
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
Time Frame
From enrollment to up to 2 years
Title
Percentage of Patients Experiencing Short-term Endocrine Toxicity
Description
The percentage of patients experiencing short-term endocrine toxicity between treatment groups is compared using the chi-square test
Time Frame
At study entry

10. Eligibility

Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen Skapek, MD
Organizational Affiliation
Children's Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Oncology Group
City
Monrovia
State/Province
California
ZIP/Postal Code
91016
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Sulindac and Tamoxifen in Treating Patients With Desmoid Tumor

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