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

Sponsor

Spectrum Pharmaceuticals, Inc (Industry)

Overall Status

Terminated

CT.gov ID

NCT01587144

Collaborator

(none)

Enrollment

Locations

Arms

9.9

Actual Duration (Months)

1.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Glioblastoma Multiforme	Drug: Lucanthone Drug: Temozolomide (TMZ) Radiation: Radiation Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, 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

Actual Study Start Date :

Jun 19, 2012

Actual Primary Completion Date :

Apr 15, 2013

Actual Study Completion Date :

Apr 15, 2013

Arms and Interventions

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: 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. 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.

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: 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.

Drug: Temozolomide (TMZ)

Radiation: Radiation

60 Gy administered in 30 fractions for 42 days in the concomitant phase.

Outcome Measures

Primary Outcome Measures

Progression Free Survival [9 months]
Progression Free Survival: defined as the time from randomization until objective tumor progression or death

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Main Inclusion Criteria:

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

May or may not have undergone surgery
Is scheduled to receive treatment with temozolomide and radiation.

Karnofsky score ≥ 70%.

Main Exclusion Criteria:

Diagnosis of recurrent brain tumor.
Received temozolomide previously.
Absolute neutrophil count ≤ 1.5 X 109/L.
Screening platelet count < 100 K/uL.
Screening bilirubin > 1.6 mg/dL.
Screening creatinine > 2.25 mg/dL in men and 1.8 mg/dL in women.
Screening ALT or AST > 2.5 times the upper limit of the laboratory reference range.
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.
Enrolled, or plans to enroll, in a concurrent treatment protocol with another investigational product.
Receiving, or plans to receive, an anti-cancer therapy other than temozolomide during the study.
Received prior chemotherapy or radiation therapy within four weeks of enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSD Moores Cancer Center	La Jolla	California	United States	92093
2	UCI Medical Center	Orange	California	United States	92868
3	Dent Neurologic Institute	Amherst	New York	United States	14226
4	Fairview Hospital Moll Cancer Center/Cleveland Clinic	Cleveland	Ohio	United States	44111
5	Cleveland Clinic	Cleveland	Ohio	United States	44195
6	Hillcrest Hospital Hirsh Cancer Center/Cleveland Clinic	Mayfield	Ohio	United States	44124
7	Gujarat Cancer Research Institute	Ahmedabad	Gujarat	India	380016
8	Jaslok Hospital & Research Centre	Mumbai	Maharashtra	India	400062
9	Bhagwan Mahaveer Cancer Hospital & Reseach Centre	Jaipur	Rajasthan	India	302017
10	Chittaranjan National Cancer Institute	Kolkata	West Bengal	India	700026

Sponsors and Collaborators

Spectrum Pharmaceuticals, Inc

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Spectrum Pharmaceuticals, Inc

ClinicalTrials.gov Identifier:

NCT01587144

Other Study ID Numbers:

SPI-LUC-11-01

First Posted:

Apr 30, 2012

Last Update Posted:

Oct 19, 2021

Last Verified:

Oct 1, 2021

Keywords provided by Spectrum Pharmaceuticals, Inc

GBM

Additional relevant MeSH terms:

Glioblastoma

Lucanthone

Temozolomide

Study Results

No Results Posted as of Oct 19, 2021