Carboplatin and Temozolomide (Temodar) for Recurrent and Symptomatic Residual Brain Metastases

• Sponsor: Ohio State University Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00362817
• Collaborator: (none)
• Enrollment: 17
• Location: 1
• Arm: 1
• Actual Duration (Months): 40
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Purpose: The primary objective of this study is to determine if chemotherapy with carboplatin and temozolomide significantly affects the response rates, or size of disease, in patients with brain metastases, originating from cancer in other parts of the body, compared to patients who have already been treated with radiation. Survival, causes of death, recurrence of disease in the central nervous system, toxicity, and quality of life will all be measured as secondary objective in this study.

Condition or Disease	Intervention/Treatment	Phase
Brain Tumor; Brain Metastases	Drug: carboplatin; Drug: temozolomide	Phase 1/Phase 2

Detailed Description

Rationale: Surgery and radiation are often used as treatments for brain metastases, or tumors in the brain that originate from other parts of the body. It is currently unknown whether patient survival or time to progression would experience additional benefits through the addition of chemotherapy. Previous research does appear to suggest that a chemotherapy regimen may improve outcomes of patients with brain metastases previously treated with radiation. The current study further evaluates this research question by providing patients with recurrent or symptomatic residual brain metastases with carboplatin and temozolomide, two chemotherapy agents. Temozolomide has demonstrated clinical antitumor efficacy against malignant gliomas and has been tested with some efficacy against several other types of cancer. This drug appears to have less adverse effects compared to other commonly used cancer drugs. Recent research indicates that temozolomide also has some efficacy against brain metastases. In addition, previous research indicates carboplatin's lack of severe toxicity in patients with this disease.

Treatment: Study participants will be treated with carboplatin and temozolomide. Carboplatin will be administered through intravenous infusions. Temozolomide will be given through oral pills. Before these drugs are administered, study participants will undergo a pre-treatment evaluation with physical and neuropsychological examinations, neuro-imaging, laboratory tests, quality of life assessment, and other procedures. Carboplatin will be given for two consecutive days. Temozolomide will be taken by study participants daily for five consecutive days. Both of these treatment schedules will be repeated every 28 days. Several tests and exams will be given throughout the study to closely monitor patients. Study treatments will be discontinued due to disease growth or unacceptable adverse events.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Multicenter Trial of Intra-Arterial Carboplatin and Oral Temozolomide for the Treatment of Recurrent and Symptomatic Residual Brain Metastases.
• Actual Study Start Date: Oct 1, 2004
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Temozolomide & Intra-Arterial (IA) carboplatin Patients will be administered Temozolomide orally once a day for 5 consecutive days and and will receive Intra Arterial Carboplatin	Drug: carboplatin; IA carboplatin 200 mg/m2/day for each arterial injection on days 1 and 2.; Other Names: Paraplatin CBDCA ; Drug: temozolomide; 150 mg/m2/day orally Days 1-5. Treatment cycles to be repeated every 4 weeks.; Other Names: Temodar

Outcome Measures

Primary Outcome Measures

1. Affects of Response Rate of Chemotherapy With Intra-arterial Carboplatin and Oral Temozolomide [up to 1 year]

   Response was evaluated by MRI Criteria (MacDonald Criteria). The MacDonald criteria for determining tumor progression is determined through assessing the increase in size of an enhancing tumor on consecutive MRI scans and clinical assessment. Complete response occurs when there is a disappearance of all enhancing tumor on consecutive MRI scans at least one month apart. Partial response occurs at a >50% reduction in size of enhancing tumor on consecutive MRI scans at least one month apart. Progressive disease occurs when there is a >25% increase in size of enhancing tumor on consecutive MRI scans. Stable disease occurs in all remaining situations.

Secondary Outcome Measures

1. Analyze Patients Time to Progression [up to 60 weeks]

   Responses to treatment was determined by comparing new enhanced MRI scans with those obtained at the previous evaluation (i.e., 2 treatment cycles ago) or with the pre-IA chemotherapy baseline scan, if it is the first follow-up MRI scan during treatment. MRI is the neuro-imaging modality of choice, since it is more accurate than CT for small tumors, multiple tumors, and tumors in the posterior fossa.58 The methodology used (techniques and equipment) must be identical for all scans. Lesions should be measured as the largest diameter seen on scan and the largest diameter perpendicular to that dimension.

2. Determine the Overall Survival of Patients [up to 64 weeks]

   From the time of protocol initiation

3. Determine the Cause of Death of Patients After Treatment [up to 1 year]

   To determine the cause of death (i.e., CNS tumor versus systemic disease progression) in patients after treatment.

4. The Incidence and Severity of Centeral Nervous System (CNS) Toxicities [up to 24 weeks]

   To determine the incidence and severity of CNS toxicity in patients treated with intra-arterial carboplatin and oral temozolomide.

5. Quality of Life Assessment [up to 2 years]

   To determine the impact of treatment on quality of life.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Pathologically confirmed systemic cancer

Exclusion Criteria:

• Pregnant

• Known CNS meningeal involvement with cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ohio State University	Columbus	Ohio	United States	43210

Sponsors and Collaborators

• Ohio State University Comprehensive Cancer Center

Investigators

• Principal Investigator: Herbert Newton, MD, Ohio State University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Jamesline

Publications

None provided.

• Responsible Party: Ohio State University Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00362817
• Other Study ID Numbers: OSU-0428
• First Posted: Aug 10, 2006
• Last Update Posted: Jun 1, 2017
• Last Verified: May 1, 2017

• Keywords provided by Ohio State University Comprehensive Cancer Center: Recurrent; Symptomatic
• Additional relevant MeSH terms: Neoplasm Metastasis; Brain Neoplasms; Carboplatin; Temozolomide

Study Results

Participant Flow

Pre-assignment Detail	All patients had received prior systemic chemotherapy for the primary tumor

Arm/Group Title	Temozolomide & Intra-Arterial (IA) Carboplatin
Arm/Group Description	Patients will be administered Temozolomide orally once a day for 5 consecutive days and and will receive Intra Arterial Carboplatin temozolomide : 150 mg/m2/day orally Days 1-5. Treatment cycles to be repeated every 4 weeks. carboplatin : IA carboplatin 200 mg/m2/day for each arterial injection on days 1 and 2.
Period Title: Overall Study
STARTED	17
COMPLETED	17
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Temozolomide & Intra-Arterial (IA) Carboplatin
Arm/Group Description	Patients will be administered Temozolomide orally once a day for 5 consecutive days and and will receive Intra Arterial Carboplatin temozolomide : 150 mg/m2/day orally Days 1-5. Treatment cycles to be repeated every 4 weeks. carboplatin : IA carboplatin 200 mg/m2/day for each arterial injection on days 1 and 2.
Overall Participants	17
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	52
Sex: Female, Male (Count of Participants)
Female	10 58.8%
Male	7 41.2%
Region of Enrollment (participants) [Number]
United States	17 100%

Outcome Measures

1. Primary Outcome

Title	Affects of Response Rate of Chemotherapy With Intra-arterial Carboplatin and Oral Temozolomide
Description	Response was evaluated by MRI Criteria (MacDonald Criteria). The MacDonald criteria for determining tumor progression is determined through assessing the increase in size of an enhancing tumor on consecutive MRI scans and clinical assessment. Complete response occurs when there is a disappearance of all enhancing tumor on consecutive MRI scans at least one month apart. Partial response occurs at a >50% reduction in size of enhancing tumor on consecutive MRI scans at least one month apart. Progressive disease occurs when there is a >25% increase in size of enhancing tumor on consecutive MRI scans. Stable disease occurs in all remaining situations.
Time Frame	up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Temozolomide & Intra-Arterial (IA) Carboplatin
Arm/Group Description	Patients will be administered Temozolomide orally once a day for 5 consecutive days and and will receive Intra Arterial Carboplatin temozolomide : 150 mg/m2/day orally Days 1-5. Treatment cycles to be repeated every 4 weeks. carboplatin : IA carboplatin 200 mg/m2/day for each arterial injection on days 1 and 2.
Measure Participants	14
Number [percentage of patients with response]	42.8

2. Secondary Outcome

Title	Analyze Patients Time to Progression
Description	Responses to treatment was determined by comparing new enhanced MRI scans with those obtained at the previous evaluation (i.e., 2 treatment cycles ago) or with the pre-IA chemotherapy baseline scan, if it is the first follow-up MRI scan during treatment. MRI is the neuro-imaging modality of choice, since it is more accurate than CT for small tumors, multiple tumors, and tumors in the posterior fossa.58 The methodology used (techniques and equipment) must be identical for all scans. Lesions should be measured as the largest diameter seen on scan and the largest diameter perpendicular to that dimension.
Time Frame	up to 60 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Temozolomide & Intra-Arterial (IA) Carboplatin
Arm/Group Description	Patients will be administered Temozolomide orally once a day for 5 consecutive days and and will receive Intra Arterial Carboplatin temozolomide : 150 mg/m2/day orally Days 1-5. Treatment cycles to be repeated every 4 weeks. carboplatin : IA carboplatin 200 mg/m2/day for each arterial injection on days 1 and 2.
Measure Participants	14
Mean (Full Range) [weeks]	22.6

3. Secondary Outcome

Title	Determine the Overall Survival of Patients
Description	From the time of protocol initiation
Time Frame	up to 64 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Temozolomide & Intra-Arterial (IA) Carboplatin
Arm/Group Description	Patients will be administered Temozolomide orally once a day for 5 consecutive days and and will receive Intra Arterial Carboplatin carboplatin: IA carboplatin 200 mg/m2/day for each arterial injection on days 1 and 2. temozolomide: 150 mg/m2/day orally Days 1-5. Treatment cycles to be repeated every 4 weeks.
Measure Participants	14
Mean (Full Range) [weeks]	25.2

4. Secondary Outcome

Title	Determine the Cause of Death of Patients After Treatment
Description	To determine the cause of death (i.e., CNS tumor versus systemic disease progression) in patients after treatment.
Time Frame	up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Temozolomide & Intra-Arterial (IA) Carboplatin
Arm/Group Description	Patients will be administered Temozolomide orally once a day for 5 consecutive days and and will receive Intra Arterial Carboplatin temozolomide : 150 mg/m2/day orally Days 1-5. Treatment cycles to be repeated every 4 weeks. carboplatin : IA carboplatin 200 mg/m2/day for each arterial injection on days 1 and 2.
Measure Participants	14
CNS tumor	0
Systemic disease progression	7

5. Secondary Outcome

Title	The Incidence and Severity of Centeral Nervous System (CNS) Toxicities
Description	To determine the incidence and severity of CNS toxicity in patients treated with intra-arterial carboplatin and oral temozolomide.
Time Frame	up to 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Temozolomide & Intra-Arterial (IA) Carboplatin
Arm/Group Description	Patients will be administered Temozolomide orally once a day for 5 consecutive days and and will receive Intra Arterial Carboplatin temozolomide : 150 mg/m2/day orally Days 1-5. Treatment cycles to be repeated every 4 weeks. carboplatin : IA carboplatin 200 mg/m2/day for each arterial injection on days 1 and 2.
Measure Participants	14
Number [patients]	0

6. Secondary Outcome

Title	Quality of Life Assessment
Description	To determine the impact of treatment on quality of life.
Time Frame	up to 2 years

Outcome Measure Data

Analysis Population Description

Quality of Life Assessment was not done.

Arm/Group Title	Temozolomide & Intra-Arterial (IA) Carboplatin
Arm/Group Description	Patients will be administered Temozolomide orally once a day for 5 consecutive days and and will receive Intra Arterial Carboplatin temozolomide : 150 mg/m2/day orally Days 1-5. Treatment cycles to be repeated every 4 weeks. carboplatin : IA carboplatin 200 mg/m2/day for each arterial injection on days 1 and 2.
Measure Participants	0

Adverse Events

Arm/Group Title	Temozolomide & Intra-Arterial (IA) Carboplatin
Arm/Group Description	Patients will be administered Temozolomide orally once a day for 5 consecutive days and and will receive Intra Arterial Carboplatin temozolomide : 150 mg/m2/day orally Days 1-5. Treatment cycles to be repeated every 4 weeks. carboplatin : IA carboplatin 200 mg/m2/day for each arterial injection on days 1 and 2.
All Cause Mortality
	Temozolomide & Intra-Arterial (IA) Carboplatin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Temozolomide & Intra-Arterial (IA) Carboplatin
	Affected / at Risk (%)	# Events
Total	0/17 (0%)
Other (Not Including Serious) Adverse Events
	Temozolomide & Intra-Arterial (IA) Carboplatin
	Affected / at Risk (%)	# Events
Total	0/17 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.