Irinotecan, Temozolomide and Bevacizumab in Combination With Existing High Dose Alkylator Based Chemotherapy for Treatment of Newly Diagnosed Patients With Desmoplastic Small Round Cell Tumor

Study Overview
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Brief Summary
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This study adds irinotecan, temozolomide and bevacizumab to the chemotherapy regimen currently used to treat Desmoplastic small round cell tumor (DSRCT). The investigators are doing this study to find out what effects, good and/or bad, the combination of irinotecan, temozolomide and bevacizumab has on the patient and the DSRCT cancer.

Official Title
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A Pilot Trial of Irinotecan, Temozolomide and Bevacizumab in Combination With Existing High Dose Alkylator Based Chemotherapy for Treatment of Newly Diagnosed Patients With Desmoplastic Small Round Cell Tumor

Conditions
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Sarcoma, Desmoplastic Small Round Cell Tumor (DSRCT)

Intervention / Treatment
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* Drug: irinotecan, temozolomide, and bevacizumab incorporated into an existing schedule of high dose alkylator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than or equal to 1 year, less than 30 years Newly diagnosed, previously untreated patients with histologically or molecularly confirmed DSRCT Adequate hematologic function: Absolute neutrophil count ≥ 1,000/mm3 Platelet count ≥ 100,000/mytm3 Adequate renal function: Normal creatinine for age OR Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 Adequate hepatic function: Total bilirubin ≤ 1.5 x the ULN for age AST ≤ 2.5 x the ULN for age [in the absence of hepatic involvement of tumor] Normal cardiac function Shortening fraction greater than or equal to 28% by echocardiogram OR Left ventricular ejection fraction (LVEF) greater than or equal to 50% on technetium-99m pertechnetate radionuclide cineangiography (MUGA) or echocardiogram Hypertension must be well controlled on stable doses of medication for at least two weeks prior to enrollment. Patients must consent to an indwelling central venous catheter. Sexually active patients of reproductive potential must be willing to use an effective method of contraception. Exclusion Criteria: Prior chemotherapy or radiotherapy Pregnant or breastfeeding females Patients with documented chronic non-healing wound, ulcer or bone fracture. Incomplete healing from previous oncologic or other major surgery. Surgical procedures: Patients who have undergone major surgery (including open biopsy, thoracotomy, organ resection, exploratory laparotomy, arteriovenous grafts) <28 days prior to enrollment will have bevacizumab dosing delayed as outlined in section 9.1 Patients must be at least 48 hours from placement of central catheter before receiving first dose of bevacizumab Minor surgical procedures (needle/laparoscopic core biopsies) for limited purposes of tissue retrieval will be allowed. Patients should not receive the first planned dose of bevacizumab until the wound is healed and 7 days have elapsed since the procedure. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation). Thrombosis: Patients must not have had a deep venous or arterial thrombosis (non-central venous catheter related) within the last three months prior to study entry. Patients with cerebrovascular accident or transient ischemic attack within 6 months of therapy are excluded History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study entry. CNS status: Patients must not have known CNS metastases or leptomeningeal disease. Screening with brain imaging is not required for asymptomatic patients. Proteinuria: Urine protein: creatinine ratio greater than or equal to 1.0 Uncontrolled hypertension (defined as SBP and/or DBP > 95th percentile for age) Prior history of hypertensive crisis or hypertensive encephalopathy NYHA Grade II or greater congestive heart failure History of myocardial infarction or unstable angina within 12 months prior to Day 1 History of stroke or transient ischemic attack Significant vascular (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1 History of hemoptysis (greater than or equal to 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1 Known hypersensitivity to any component of bevacizumab

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 29 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy<br>This is a pilot study to evaluate the acute toxicities and activity of irinotecan, temozolomide, and bevacizumab incorporated into an existing schedule of high dose alkylator based therapy in newly diagnosed patients with DSRCT. | Drug: irinotecan, temozolomide, and bevacizumab incorporated into an existing schedule of high dose alkylator<br>* Two cycles of the investigational combination irinotecan, temozolomide and bevacizumab- will be given followed by conventional chemotherapy with a modified P6 approach and surgical local control. Completion of modified P6 chemotherapy will be followed by a second-look surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To define the tolerability | of irinotecan, temozolomide and bevacizumab in patients with newly diagnosed DSRCT | 2 years | 
| To define adverse event profile | of irinotecan, temozolomide and bevacizumab in patients with newly diagnosed DSRCT | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To estimate the response rate of two cycles of irinotecan, temozolomide and bevacizumab | In patients with measurable disease. added to the initial treatment of patients with Desmoplastic small round cell tumor (DSRCT) | 2 years | 
| To estimate survival | with the addition of irinotecan, temozolomide and bevacizumab to the initial treatment of patients with DSRCT | 2 years | 
| To estimate time to progression | with the addition of irinotecan, temozolomide and bevacizumab to the initial treatment of patients with DSRCT | 2 years | 
| To assess use of 18FDG PET-CT | as an early indicator of response in those patients with measurable or evaluable disease | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BEVACIZUMAB (AVASTIN), IRINOTECAN (CPT-11) CAMPTOSAR, TEMOZOLOMIDE, DSRCT, 10-091