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

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 15

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Chemotherapy	irinotecan, temozolomide, and bevacizumab incorporated into an existing schedule of high dose alkylator	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.

Primary Outcome Measures

Name	Time	Method
To define the tolerability	2 years	of irinotecan, temozolomide and bevacizumab in patients with newly diagnosed DSRCT
To define adverse event profile	2 years	of irinotecan, temozolomide and bevacizumab in patients with newly diagnosed DSRCT

Secondary Outcome Measures

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

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

Recruitment & Eligibility

Study & Design

Trial Locations

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