Desmoid Tumor
Conditions
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.
Interventions
DRUGtamoxifen citrate
Given orally
DRUGsulindac
Given orally
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Children's Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 70 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Ineligible | 11 |
| Overall Study | Lack of Efficacy | 24 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Physician Decision | 7 |
| Overall Study | Withdrawal by Subject | 14 |
Baseline characteristics
| Characteristic | Treatment (Enzyme Inhibitor Therapy, Anti-estrogen Therapy) |
|---|---|
| Age, Categorical <=18 years | 62 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) White | 51 Participants |
| Region of Enrollment Canada | 7 participants |
| Region of Enrollment United States | 63 participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 42 / 59 |
| serious Total, serious adverse events | 2 / 59 |
Outcome results
Primary
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
Time frame: Up to 12 months
Population: All eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Enzyme Inhibitor Therapy, Anti-estrogen Therapy) | Percentage of Patients Experiencing a Grade 3 or Higher Adverse Event During Therapy. | 3.4 Percentage of participants |
Primary
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.
Time frame: Up to 2 years
Population: All eligible patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Enzyme Inhibitor Therapy, Anti-estrogen Therapy) | Percentage of Patients Failure Free at 2 Years Following Study Entry | 36 percentage of participants |
Secondary
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.
Time frame: From baseline to up to 5 years
Population: Outcome not reported because the required data were not recorded.
Secondary
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
Time frame: At study entry
Population: Data not available for analysis due to no data were collected.
Secondary
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
Time frame: From enrollment to up to 2 years
Population: Data not available for analysis due to no data were collected
Secondary
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)
Time frame: Baseline up to 5 years
Population: All eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Enzyme Inhibitor Therapy, Anti-estrogen Therapy) | Percentage of Patients With Tumor Response From Imaging | 8.0 Percentage of participants |