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

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

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).

Study Overview

• Status: Terminated
• Conditions: Glioblastoma Multiforme
• Intervention / Treatment: Drug: Temozolomide (TMZ); Radiation: Radiation; Drug: Placebo; Drug: Lucanthone

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • Gujarat
    • Ahmedabad, Gujarat, India, 380016
      • Gujarat Cancer Research Institute
  • Maharashtra
    • Mumbai, Maharashtra, India, 400062
      • Jaslok Hospital & Research Centre
  • Rajasthan
    • Jaipur, Rajasthan, India, 302017
      • Bhagwan Mahaveer Cancer Hospital & Reseach Centre
  • West Bengal
    • Kolkata, West Bengal, India, 700026
      • Chittaranjan National Cancer Institute
• United States
  • California
    • La Jolla, California, United States, 92093
      • UCSD Moores Cancer Center
    • Orange, California, United States, 92868
      • UCI Medical Center
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurologic Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44111
      • Fairview Hospital Moll Cancer Center/Cleveland Clinic
    • Mayfield, Ohio, United States, 44124
      • Hillcrest Hospital Hirsh Cancer Center/Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will receive a matching placebo as an adjunct in 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).	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 common terminology criteria (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; Placebo will be given as an oral at 10-15 mg/kg/day for 6 weeks during the concomitant phase. In the maintenance phase, placebo will be administered on days 1-5 of a 28-day cycle for 6 cycles.
Active Comparator: Lucanthone; Participants will receive Lucanthone as an adjunct in 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).	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 common terminology criteria (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: Lucanthone; Lucanthone will be given as an oral at 10-15 mg/kg/day for 6 weeks during the concomitant phase. In the maintenance phase, placebo will be administered on days 1-5 of a 28-day cycle for 6 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Progression Free Survival: defined as the time from randomization until objective tumor progression or death	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Fraction of patients with a Complete Response (CR) or Partial Response (PR) at anytime through the 12 months visit.	one year
Overall Survival	Overall Survival: The time from randomization until death.	one year
Safety Profile of Lucanthone	Safety Profile of Lucanthone at 10-15 mg/kg/day.	one year

Collaborators and Investigators

• Sponsor: Spectrum Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2012
• Primary Completion (Actual): April 15, 2013
• Study Completion (Actual): April 15, 2013

Study Registration Dates

• First Submitted: April 11, 2012
• First Submitted That Met QC Criteria: April 27, 2012
• First Posted (Estimate): April 30, 2012

Study Record Updates

• Last Update Posted (Actual): October 19, 2021
• Last Update Submitted That Met QC Criteria: October 18, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: GBM
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Antiparasitic Agents; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Temozolomide; Lucanthone
• Other Study ID Numbers: SPI-LUC-11-01