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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01189643
First received: August 25, 2010
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention
Sarcoma
Desmoplastic Small Round Cell Tumor (DSRCT)
Drug: irinotecan, temozolomide, and bevacizumab incorporated into an existing schedule of high dose alkylator

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To define the tolerability [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    of irinotecan, temozolomide and bevacizumab in patients with newly diagnosed DSRCT

  • To define adverse event profile [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    In patients with measurable disease. added to the initial treatment of patients with Desmoplastic small round cell tumor (DSRCT)

  • To estimate survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    with the addition of irinotecan, temozolomide and bevacizumab to the initial treatment of patients with DSRCT

  • To estimate time to progression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    with the addition of irinotecan, temozolomide and bevacizumab to the initial treatment of patients with DSRCT

  • To assess use of 18FDG PET-CT [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    as an early indicator of response in those patients with measurable or evaluable disease


Estimated Enrollment: 15
Study Start Date: August 2010
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chemotherapy
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
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.

  Eligibility

Ages Eligible for Study:   1 Year to 29 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01189643

Contacts
Contact: Heather Magnan, MD 212-639-7937
Contact: Paul Meyers, MD 212-639-5952

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Heather Magnan, MD    212-639-7937      
Contact: Paul Meyers, MD    212-639-5952      
Principal Investigator: Heather Magnan, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Genentech
Investigators
Principal Investigator: Heather Magnan, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01189643     History of Changes
Other Study ID Numbers: 10-091
Study First Received: August 25, 2010
Last Updated: June 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
BEVACIZUMAB (AVASTIN)
IRINOTECAN (CPT-11) CAMPTOSAR
TEMOZOLOMIDE
DSRCT
10-091

Additional relevant MeSH terms:
Desmoplastic Small Round Cell Tumor
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Alkylating Agents
Temozolomide
Dacarbazine
Irinotecan
Bevacizumab
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014