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

Phase I/II Multicenter Trial of Intra-Arterial Carboplatin and Oral Temozolomide for the Treatment of Recurrent and Symptomatic Residual Brain Metastases.

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.

Study Overview

• Status: Completed
• Conditions: Brain Tumor; Brain Metastases
• Intervention / Treatment: Drug: carboplatin; Drug: temozolomide

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 Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University

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

Inclusion Criteria:

• Pathologically confirmed systemic cancer

Exclusion Criteria:

• Pregnant
• Known CNS meningeal involvement with cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: CBDCA; Paraplatin; Drug: temozolomide; 150 mg/m2/day orally Days 1-5. Treatment cycles to be repeated every 4 weeks.; Other Names: Temodar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Affects of Response Rate of Chemotherapy With Intra-arterial Carboplatin and Oral Temozolomide	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.	up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analyze Patients Time to Progression	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.	up to 60 weeks
Determine the Overall Survival of Patients	From the time of protocol initiation	up to 64 weeks
Determine the Cause of Death of Patients After Treatment	To determine the cause of death (i.e., CNS tumor versus systemic disease progression) in patients after treatment.	up to 1 year
The Incidence and Severity of Centeral Nervous System (CNS) Toxicities	To determine the incidence and severity of CNS toxicity in patients treated with intra-arterial carboplatin and oral temozolomide.	up to 24 weeks
Quality of Life Assessment	To determine the impact of treatment on quality of life.	up to 2 years

Collaborators and Investigators

• Sponsor: Ohio State University Comprehensive Cancer Center
• Investigators: Principal Investigator: Herbert Newton, MD, Ohio State University

Publications and helpful links

Helpful Links

• Jamesline

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2004
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: August 8, 2006
• First Submitted That Met QC Criteria: August 9, 2006
• First Posted (Estimate): August 10, 2006

Study Record Updates

• Last Update Posted (Actual): June 1, 2017
• Last Update Submitted That Met QC Criteria: May 1, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Recurrent; Symptomatic
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Carboplatin; Temozolomide
• Other Study ID Numbers: OSU-0428