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Study to Evaluate the Efficacy and Safety of Temozolomide in Subjects With Brain Metastases of Either Malignant Melanoma, Breast, or Non-small Cell Lung Cancer (P02064)

Primary Purpose

Metastases of Central Nervous System, Melanoma, Breast Neoplasm

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Temozolomide
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastases of Central Nervous System

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Cytological/histological diagnosis of either melanoma, non-small cell lung cancer and breast;
  • Brain metastases >=1 cm presenting or in progression following >=4 weeks time interval free from previous malignancy-specific chemotherapy, hormone therapy, or other medical therapies;
  • Magnetic resonance imaging suspected brain metastases; patients with brain lesion(s) not univocal as brain metastases must have negative radiolabeled leukocyte brain scan to rule out infectious non-malignant disease; all neuroradiological studies (baseline and treatment outcome evaluation), except for emergency exams must be performed after 10 days of unchanged schedule of dexamethasone, and obtained in the axial-coronal-sagittal planes in T1 and T2 before and after gadolinium enhancement.
  • Presence of al least one bidimensionally measurable and not previously irradiated metastasis.
  • Age <=70 years.
  • Performance status 0-2 (ECOG-WHO scale).
  • Blood leukocytes >=3.5 x 10^9/L and platelets >=100 x 10^9/L.
  • Bilirubin <=25 M/L.
  • Seric transaminases <=2 x upper limit of normal values.
  • Creatinine <=150 M/L, creatinine clearance >=60 mL/min.
  • Signed written informed consent.

Exclusion Criteria:

  • Diabetes not allowing administration of adequate doses of dexamethasone at least during the first 2 months of treatment.
  • Previous whole brain irradiation.
  • Brain metastases eligible to neurosurgery or stereotactic radiation therapy.
  • Previous or current malignancies at other sites with the exception of adequately treated in situ carcinoma of the cervix or basal and squamous carcinoma of the skin.
  • Pregnant or nursing women.
  • Acute infection requiring intravenous antibiotics.
  • Severe vomiting or medical condition which could interfere with oral medication intake.
  • Anticonvulsant chronic therapy.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    Subjects with melanoma

    Subjects with breast cancer

    Subjects with non-small cell lung cancer

    Arm Description

    Outcomes

    Primary Outcome Measures

    Best response related to brain metastases observed during the study period.

    Secondary Outcome Measures

    Progression-free survival, brain progression-free survival, and overall survival.
    Adverse events according to NCI CTC grading system of toxicity.

    Full Information

    First Posted
    January 15, 2009
    Last Updated
    May 8, 2017
    Sponsor
    Merck Sharp & Dohme LLC
    Collaborators
    Quintiles, Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00831545
    Brief Title
    Study to Evaluate the Efficacy and Safety of Temozolomide in Subjects With Brain Metastases of Either Malignant Melanoma, Breast, or Non-small Cell Lung Cancer (P02064)
    Official Title
    Multicenter Phase 2 Evaluation of Temozolomide for Treatment of Brain Metastases of Either Malignant Melanoma, Breast and Non-small Cell Lung Cancer.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    December 1, 2000 (Actual)
    Primary Completion Date
    October 20, 2006 (Actual)
    Study Completion Date
    October 20, 2006 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC
    Collaborators
    Quintiles, Inc.

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The study implies a 2 step study design. Patients are enrolled into 3 separate groups for melanoma, breast, and non-small cell lung cancer. In the first step, 21 patients per disease group are enrolled. If >=2 objective responses (SD, PR, or CR) out of 21 evaluable patients are observed, enrollment continues for other 45 patients as a whole, where response will be positively evaluated if >=10 patients will respond. If <2 objective responses out of 21 evaluable patients per disease group are observed, this(ese) group(s) will no longer be treated with temozolomide.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Metastases of Central Nervous System, Melanoma, Breast Neoplasm, Carcinoma, Non-Small-Cell Lung

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    162 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Subjects with melanoma
    Arm Type
    Experimental
    Arm Title
    Subjects with breast cancer
    Arm Type
    Experimental
    Arm Title
    Subjects with non-small cell lung cancer
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    Temozolomide
    Other Intervention Name(s)
    SCH 52365
    Intervention Description
    150 mg/m2 given once a day for 7 consecutive days (Days 1 through 7) repeated every other week until disease progression or toxicity or for a maximum of one year. After amendment, schedule was modified: a second rest week was added after the second wash-out week (Days 1 through 7, 15 through 21 every 35).
    Primary Outcome Measure Information:
    Title
    Best response related to brain metastases observed during the study period.
    Time Frame
    After 2 months of initial treatment. If response or stable disease evaluations were performed every 3 months. Subsequently, an additional check up was added by amendment: a follow up check was performed after 4 weeks.
    Secondary Outcome Measure Information:
    Title
    Progression-free survival, brain progression-free survival, and overall survival.
    Time Frame
    After 2 months of initial treatment. If response or stable disease evaluations were performed every 3 months. Subsequently, an additional check up was added by amendment: a follow up check was performed after 4 weeks.
    Title
    Adverse events according to NCI CTC grading system of toxicity.
    Time Frame
    Throughout the study.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Cytological/histological diagnosis of either melanoma, non-small cell lung cancer and breast; Brain metastases >=1 cm presenting or in progression following >=4 weeks time interval free from previous malignancy-specific chemotherapy, hormone therapy, or other medical therapies; Magnetic resonance imaging suspected brain metastases; patients with brain lesion(s) not univocal as brain metastases must have negative radiolabeled leukocyte brain scan to rule out infectious non-malignant disease; all neuroradiological studies (baseline and treatment outcome evaluation), except for emergency exams must be performed after 10 days of unchanged schedule of dexamethasone, and obtained in the axial-coronal-sagittal planes in T1 and T2 before and after gadolinium enhancement. Presence of al least one bidimensionally measurable and not previously irradiated metastasis. Age <=70 years. Performance status 0-2 (ECOG-WHO scale). Blood leukocytes >=3.5 x 10^9/L and platelets >=100 x 10^9/L. Bilirubin <=25 M/L. Seric transaminases <=2 x upper limit of normal values. Creatinine <=150 M/L, creatinine clearance >=60 mL/min. Signed written informed consent. Exclusion Criteria: Diabetes not allowing administration of adequate doses of dexamethasone at least during the first 2 months of treatment. Previous whole brain irradiation. Brain metastases eligible to neurosurgery or stereotactic radiation therapy. Previous or current malignancies at other sites with the exception of adequately treated in situ carcinoma of the cervix or basal and squamous carcinoma of the skin. Pregnant or nursing women. Acute infection requiring intravenous antibiotics. Severe vomiting or medical condition which could interfere with oral medication intake. Anticonvulsant chronic therapy.

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    19767314
    Citation
    Siena S, Crino L, Danova M, Del Prete S, Cascinu S, Salvagni S, Schiavetto I, Vitali M, Bajetta E. Dose-dense temozolomide regimen for the treatment of brain metastases from melanoma, breast cancer, or lung cancer not amenable to surgery or radiosurgery: a multicenter phase II study. Ann Oncol. 2010 Mar;21(3):655-661. doi: 10.1093/annonc/mdp343. Epub 2009 Sep 18.
    Results Reference
    result
    Available IPD and Supporting Information:
    Available IPD/Information Type
    CSR Synopsis Links
    Available IPD/Information URL
    http://www.merck.com/clinical-trials/policies-perspectives.html

    Learn more about this trial

    Study to Evaluate the Efficacy and Safety of Temozolomide in Subjects With Brain Metastases of Either Malignant Melanoma, Breast, or Non-small Cell Lung Cancer (P02064)

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