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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

Primary Purpose

Sarcoma, Desmoplastic Small Round Cell Tumor (DSRCT)

Status
Active
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
irinotecan, temozolomide, and bevacizumab incorporated into an existing schedule of high dose alkylator
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sarcoma focused on measuring BEVACIZUMAB (AVASTIN), IRINOTECAN (CPT-11) CAMPTOSAR, TEMOZOLOMIDE, DSRCT, 10-091

Eligibility Criteria

1 Year - 29 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Chemotherapy

Arm Description

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.

Outcomes

Primary Outcome Measures

To define the tolerability
of irinotecan, temozolomide and bevacizumab in patients with newly diagnosed DSRCT
To define adverse event profile
of irinotecan, temozolomide and bevacizumab in patients with newly diagnosed DSRCT

Secondary Outcome Measures

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)
To estimate survival
with the addition of irinotecan, temozolomide and bevacizumab to the initial treatment of patients with DSRCT
To estimate time to progression
with the addition of irinotecan, temozolomide and bevacizumab to the initial treatment of patients with DSRCT
To assess use of 18FDG PET-CT
as an early indicator of response in those patients with measurable or evaluable disease

Full Information

First Posted
August 25, 2010
Last Updated
September 1, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01189643
Brief Title
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
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 2010 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Genentech, Inc.

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoma, Desmoplastic Small Round Cell Tumor (DSRCT)
Keywords
BEVACIZUMAB (AVASTIN), IRINOTECAN (CPT-11) CAMPTOSAR, TEMOZOLOMIDE, DSRCT, 10-091

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Chemotherapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
irinotecan, temozolomide, and bevacizumab incorporated into an existing schedule of high dose alkylator
Intervention Description
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.
Primary Outcome Measure Information:
Title
To define the tolerability
Description
of irinotecan, temozolomide and bevacizumab in patients with newly diagnosed DSRCT
Time Frame
2 years
Title
To define adverse event profile
Description
of irinotecan, temozolomide and bevacizumab in patients with newly diagnosed DSRCT
Time Frame
2 years
Secondary Outcome Measure Information:
Title
To estimate the response rate of two cycles of irinotecan, temozolomide and bevacizumab
Description
In patients with measurable disease. added to the initial treatment of patients with Desmoplastic small round cell tumor (DSRCT)
Time Frame
2 years
Title
To estimate survival
Description
with the addition of irinotecan, temozolomide and bevacizumab to the initial treatment of patients with DSRCT
Time Frame
2 years
Title
To estimate time to progression
Description
with the addition of irinotecan, temozolomide and bevacizumab to the initial treatment of patients with DSRCT
Time Frame
2 years
Title
To assess use of 18FDG PET-CT
Description
as an early indicator of response in those patients with measurable or evaluable disease
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
29 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emily Slotkin, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mskcc.org/mskcc/html/44.cfm
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

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

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