Irinotecan and Temozolomide in Combination With Existing High Dose Alkylator Based Chemotherapy for Treatment of Patients With Newly Diagnosed Ewing Sarcoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01864109
First received: May 23, 2013
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to find out what effects, good and/or bad, the combination of irinotecan and temozolomide has on Ewing sarcoma.

Irinotecan and temozolomide are chemotherapy drugs that are used very often to treat pediatric patients at MSKCC. The investigators have used these two drugs for many years to treat patients with Ewing sarcoma whose cancer has relapsed.

For patients with newly diagnosed Ewing sarcoma the current standard of care at MSKCC is a five drug chemotherapy regimen in combination with surgery and/or radiation therapy. This standard regimen is called the EFT regimen. . Some patients with Ewing sarcoma do not have their cancer cured by the chemotherapy and surgery/radiation therapy.

This study adds the chemotherapy drugs called irinotecan and temozolomide to the standard EFT regimen. The investigators are trying to improve the success of standard therapy by adding these drugs. The use of irinotecan and temozolomide in this study is experimental because they have not been used before in patients with newly diagnosed Ewing sarcoma. However the investigators have found these drugs to be effective in patients with relapsed Ewing sarcoma. It is not known if adding these two drugs will improve the outcomes of patients treated for Ewing sarcoma.


Condition Intervention Phase
Newly Diagnosed Ewing Sarcoma
Drug: Cyclophosphamide
Device: Doxorubicin
Drug: Vincristine
Device: Ifosfamide
Drug: Etoposide
Procedure: Surgery
Radiation: Radiation Therapy*
Drug: Temozolomide
Drug: Irinotecan
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Irinotecan and Temozolomide in Combination With Existing High Dose Alkylator Based Chemotherapy for Treatment of Patients With Newly Diagnosed Ewing Sarcoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • event free survival of patients with localized disease [ Time Frame: 4 years ] [ Designated as safety issue: No ]

    We will determine event free survival from the time of study entry for all patients. An event would include death from any cause, progression of tumor, recurrence of tumor, or second malignancy.

    Progressive disease (PD) will be defined according to RECIST 1.1.



Secondary Outcome Measures:
  • event free survival of patients with metastatic disease [ Time Frame: 4 years ] [ Designated as safety issue: No ]

    We will determine event free survival from the time of study entry for all patients. An event would include death from any cause, progression of tumor, recurrence of tumor, or second malignancy.

    Progressive disease (PD) will be defined according to RECIST 1.1.


  • adverse event profile [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Toxicities are graded by the Common Toxicity Criteria (Version 4.0) developed by the National Cancer Institute (NCI) of the USA.


Estimated Enrollment: 83
Study Start Date: May 2013
Estimated Study Completion Date: May 2019
Estimated Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Patients with localized disease

Patients with localized disease will receive six cycles of the combination as "maintenance" therapy following standard chemotherapy.

  • Cycles 4-6 will include:

    • Ifosfamide 2,800 mg/m2/day on days 1-5
    • Etoposide 100 mg/m2/day on days 1-5
  • Cycle 7 will include :

    • Cyclophosphamide will be given on days 1 and 2 at a dose of 2,100 mg/m2/day, or for patients < 10 years of age at a dose of 70 mg/kg/day
    • Doxorubicin will be given on days 1 and 2 at a dose of 37.5 mg/m2/day
    • Vincristine will be given on day 1 at a dose of 2 mg/m2 or 0.067 mg/kg (whichever is lower, to a max dose of 2 mg)
  • Cycles 8-13 will include:

    • Irinotecan will be given on 10 days over weeks 1 and 2 of a cycle at a dose of 20 mg/m2/day intravenously
    • Temozolomide will be given daily on the first 5 days of irinotecan administration at a dose of 100 mg/m2/day orally or intravenously
Drug: Cyclophosphamide Device: Doxorubicin Drug: Vincristine Device: Ifosfamide Drug: Etoposide Procedure: Surgery Radiation: Radiation Therapy*
If local control includes RT, RT should be given concurrently with chemotherapy cycles
Drug: Temozolomide Drug: Irinotecan
Experimental: Patients with metastatic disease

Patients with metastatic disease will receive ten cycles of the combination intercalated between the final 4 cycles of standard chemotherapy.

  • Cycles 4, 5, 7, 8, 10, 11, 13, 14, 16, and 17 will include:

    • Irinotecan will be given on 10 days over weeks 1 and 2 of a cycle at a dose of 20 mg/m2/day intravenously
    • Temozolomide will be given daily on the first 5 days of irinotecan administration at a dose of 100 mg/m2/day orally or intravenously
  • Cycles 6, 9, and 12 will include:

    • Ifosfamide 2,800 mg/m2/day on days 1-5
    • Etoposide 100 mg/m2/day on days 1-5
  • Cycle 15 will include:

    • Cyclophosphamide will be given on days 1 and 2 at a dose of 2,100 mg/m2/day, or for patients < 10 years of age at a dose of 70 mg/kg/day
    • Doxorubicin will be given on days 1 and 2 at a dose of 37.5 mg/m2/day
    • Vincristine will be given on day 1 at a dose of 2 mg/m2 or 0.067 mg/kg (whichever is lower, to a max dose of 2 mg)
Drug: Cyclophosphamide Device: Doxorubicin Drug: Vincristine Device: Ifosfamide Drug: Etoposide Procedure: Surgery Radiation: Radiation Therapy*
If local control includes RT, RT should be given concurrently with chemotherapy cycles
Drug: Temozolomide Drug: Irinotecan

  Eligibility

Ages Eligible for Study:   1 Year to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age greater than or equal to one year and less than or equal to 40 years at the time of diagnosis
  • Newly diagnosed, previously untreated patients with histologically or molecularly confirmed Ewing sarcoma
  • Adequate hematologic function:

    • Absolute neutrophil count ≥ 1,000/μL
    • Platelet count ≥ 100,000/μL
  • Adequate renal function:

    • Normal creatinine for age (See table below) OR
    • Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 Age(Years) Maximum Serum Creatinine (mg/dL) ≤ 5 0.8 6 to ≤ 10 1 11 to ≤ 15 1.2 ≥ 16 1.5

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]
  • ALT ≤ 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

    • 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 (other than limited, emergent radiotherapy for treatment of eg. spinal cord compromise or threatened airway)
  • Pregnant or breastfeeding females
  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: NCT01864109

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
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: NCT01864109     History of Changes
Other Study ID Numbers: 13-068
Study First Received: May 23, 2013
Last Updated: June 19, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
CYCLOPHOSPHAMIDE (CYTOXAN)
DOXORUBICIN/ADRIAMYCIN
ETOPOSIDE (VP-16)
IFOSFAMIDE
IRINOTECAN (CPT-11) CAMPTOSAR
TEMOZOLOMIDE
VINCRISTINE
13-068

Additional relevant MeSH terms:
Sarcoma, Ewing's
Sarcoma
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Alkylating Agents
Cyclophosphamide
Ifosfamide
Isophosphamide mustard
Temozolomide
Dacarbazine
Etoposide phosphate
Irinotecan
Doxorubicin
Etoposide
Vincristine
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on July 22, 2014