Safety and Efficacy Study of Lucanthone When Used in Combination With Temozolomide(TMZ) and Radiation to Treat Glioblastoma Multiforme(GBM)

This study has been terminated.
(Sponsor's decision)
Sponsor:
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01587144
First received: April 11, 2012
Last updated: October 30, 2013
Last verified: October 2013
  Purpose

The purpose of the study is to determine the effectiveness of an investigational drug called lucanthone, when combined with temozolomide (TMZ) and radiation in the treatment of Glioblastoma Multiforme (GBM).


Condition Intervention Phase
Glioblastoma Multiforme
Drug: Lucanthone
Drug: Temozolomide (TMZ)
Radiation: Radiation
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: An International, Multi-Center, Randomized, Double Blind Placebo Controlled Phase II Study to Evaluate the Safety and Efficacy of Lucanthone Administered as an Adjunct to Radiation and Temozolomide for Primary Therapy of Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by Spectrum Pharmaceuticals, Inc:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    Progression Free Survival: defined as the time from randomization until objective tumor progression or death


Secondary Outcome Measures:
  • Objective response rate (ORR) [ Time Frame: one year ] [ Designated as safety issue: No ]
    Fraction of patients with a CR or PR at anytime through the 12 months visit.

  • Overall Survival [ Time Frame: one year ] [ Designated as safety issue: No ]
    Overal Survivial: The time from randomization until death.

  • Safety Profile of Lucanthone [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    Safety Profile of Lucanthone at 10-15 mg/kg/day.


Enrollment: 18
Study Start Date: March 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: TMZ + Radiation + Placebo
Subjects will be randomly assigned to Lucanthone or Placebo arm in ratio of 1:1. The treatment period will be in two phases: an initial six weeks of concomitant therapy with TMZ and radiation, followed by a maintenance phase of six cycles of TMZ given on Days 1 to 5 of a 28-day cycle (+/- 3 days). Lucanthone/placebo will be given as an adjunct to TMZ in both phases.
Drug: Temozolomide (TMZ)
TMZ is administered at 75mg/m2 daily for 42 days during the concomitant phase. TMZ is administered for an additional 6 cycles of maintenance treatment. Dosage in Cycle 1 (maintenance) is 150 mg/m2 once daily for 5 days followed by 23 days without treatment. Cycles 2-6: At the start of Cycle 2, the dose can be escalated to 200 mg/m2, if the CTC nonhematologic toxicity for Cycle 1 is Grade ≤2 (except for alopecia, nausea, and vomiting), absolute neutrophil count (ANC) is ≥1.5 x 109/L, and the platelet count is ≥100 x 109/L. The dose remains at 200 mg/m2 per day for the first 5 days of each subsequent cycle except if toxicity occurs.
Radiation: Radiation
60 Gy administered in 30 fractions for 42 days in the concomitant phase.
Drug: Placebo
Lucanthone or Placebo will be given as an oral at 10-15 mg/kg/day for 6 weeks along with radiation and TMZ during the concomitant phase. In the maintenance phase, lucanthone/placebo will be administered along with TMZ on days 1-5 of a 28-day cycle for 6 cycles.
Active Comparator: Lucanthone + TMZ + Radiation
Subjects will be randomly assigned to Lucanthone or Placebo arm in ratio of 1:1. The treatment period will be in two phases: an initial six weeks of concomitant therapy with TMZ and radiation, followed by a maintenance phase of six cycles of TMZ given on Days 1 to 5 of a 28-day cycle (+/- 3 days). Lucanthone/placebo will be given as an adjunct to TMZ in both phases.
Drug: Lucanthone
Lucanthone or Placebo will be given as an oral at 10-15 mg/kg/day for 6 weeks along with radiation and TMZ during the concomitant phase. In the maintenance phase, lucanthone/placebo will be administered along with TMZ on days 1-5 of a 28-day cycle for 6 cycles.
Drug: Temozolomide (TMZ)
TMZ is administered at 75mg/m2 daily for 42 days during the concomitant phase. TMZ is administered for an additional 6 cycles of maintenance treatment. Dosage in Cycle 1 (maintenance) is 150 mg/m2 once daily for 5 days followed by 23 days without treatment. Cycles 2-6: At the start of Cycle 2, the dose can be escalated to 200 mg/m2, if the CTC nonhematologic toxicity for Cycle 1 is Grade ≤2 (except for alopecia, nausea, and vomiting), absolute neutrophil count (ANC) is ≥1.5 x 109/L, and the platelet count is ≥100 x 109/L. The dose remains at 200 mg/m2 per day for the first 5 days of each subsequent cycle except if toxicity occurs.
Radiation: Radiation
60 Gy administered in 30 fractions for 42 days in the concomitant phase.

Detailed Description:

This is an international, multicenter, randomized, double blind placebo controlled phase II study to evaluate the safety and efficacy of lucanthone administered as an adjunct to patients receiving primary treatment of GBM with temozolomide and radiation. Eligible patients will be randomized to lucanthone or placebo arm in ratio of 1:1. The treatment period will be in two phases ; an initial six weeks of concomitant therapy with temozolomide and radiation, followed by a maintenance phase of six cycles of temozolomide given on Days 1 to 5 of a 28- day cycle (+/- 3 days). Lucanthone / placebo will be given as an add on in both concomitant and maintenance phases.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  1. 18 and 70 years of age in India, 18 years and above in US
  2. Histologically proven GBM who

    • May or may not have undergone surgery
    • Is scheduled to receive treatment with temozolomide and radiation.
  3. Karnofsky score ≥ 70%.

Main Exclusion Criteria:

  1. Diagnosis of recurrent brain tumor.
  2. Received temozolomide previously.
  3. Absolute neutrophil count ≤ 1.5 X 109/L.
  4. Screening platelet count < 100 K/uL.
  5. Screening bilirubin > 1.6 mg/dL.
  6. Screening creatinine > 2.25 mg/dL in men and 1.8 mg/dL in women.
  7. Screening ALT or AST > 2.5 times the upper limit of the laboratory reference range.
  8. Unstable medical condition or significant comorbid pathophysiology (e.g. active infection, poorly controlled diabetes, unstable angina, severe heart failure) that would interfere with his/her participation in the study.
  9. Enrolled, or plans to enroll, in a concurrent treatment protocol with another investigational product.
  10. Receiving, or plans to receive, an anti-cancer therapy other than temozolomide during the study.
  11. Received prior chemotherapy or radiation therapy within four weeks of enrollment.
  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: NCT01587144

Locations
United States, California
UCSD Moores Cancer Center
La Jolla, California, United States, 92093
UCI Medical Center
Orange, California, United States, 92868
United States, New York
Dent Neurologic Institute
Amherst, New York, United States, 14226
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Fairview Hospital Moll Cancer Center/Cleveland Clinic
Cleveland, Ohio, United States, 44111
Hillcrest Hospital Hirsh Cancer Center/Cleveland Clinic
Mayfield, Ohio, United States, 44124
India
Gujarat Cancer Research Institute
Ahmedabad, Gujarat, India, 380016
Jaslok Hospital & Research Centre
Mumbai, Maharashtra, India, 400062
Bhagwan Mahaveer Cancer Hospital & Reseach Centre
Jaipur, Rajasthan, India, 302017
Chittaranjan National Cancer Institute
Kolkata, West Bengal, India, 700026
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
Investigators
Principal Investigator: Lazlo Mechtler, MD Dent Neurologic Institute
Principal Investigator: Manmeet Ahluwalia, MD The Cleveland Clinic
Principal Investigator: Santosh Kesari, MD University of California, San Diego
Principal Investigator: Jose Carrillo, MD UCI Medical Center
Principal Investigator: Rakeshkumar Vyas Gujarat Cancer & Research Institute
Principal Investigator: Suresh Advani Jaslok Hospital & Research Centre
Principal Investigator: Naresh Somani Bhagwan Mahaveer Cancer Hosptial & Research Centre
Principal Investigator: Jaydip Biswas Chittaranjan National Cancer Institute
  More Information

No publications provided

Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT01587144     History of Changes
Other Study ID Numbers: SPI-LUC-11-01
Study First Received: April 11, 2012
Last Updated: October 30, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Spectrum Pharmaceuticals, Inc:
GBM

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Lucanthone
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Schistosomicides
Antiplatyhelmintic Agents
Anthelmintics
Antiparasitic Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on October 19, 2014