Motexafin Gadolinium and Doxorubicin in Treating Patients With Advanced Cancer
Study Details
Study Description
Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Motexafin gadolinium may increase the effectiveness of doxorubicin by making tumor cells more sensitive to the drug.
PURPOSE: Phase I trial to study the effectiveness of combining motexafin gadolinium with doxorubicin in treating patients who have recurrent or metastatic cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
OBJECTIVES:
-
Determine the maximum tolerated dose of motexafin gadolinium and doxorubicin in patients with advanced malignancies.
-
Determine the dose-limiting toxicity of this regimen in these patients.
-
Determine the safety and tolerability of this regimen in these patients.
-
Determine the pharmacokinetics of this regimen in these patients.
-
Evaluate the tumor response in patients treated with this regimen.
OUTLINE: This is a dose-escalation, multicenter study. Patients are assigned to 1 of 2 groups.
Group A:
-
Course 1: Patients receive motexafin gadolinium IV over 30 minutes on days 1, 8, 9, and 10 and doxorubicin IV over 15 minutes on day 8.
-
Course 2: 28 days after the beginning of course 1, patients receive doxorubicin IV over 15 minutes.
-
Courses 3-6: Beginning 21 days after course 2, patients receive doxorubicin IV over 15 minutes on day 1 and motexafin gadolinium IV over 30 minutes on days 1-3. Treatment repeats every 21 days.
Group B:
-
Course 1: Patients receive motexafin gadolinium IV over 30 minutes on day 1 and doxorubicin IV over 15 minutes on day 8.
-
Course 2: 28 days after the beginning of course 1, patients receive doxorubicin IV over 15 minutes on day 1 and motexafin gadolinium IV over 30 minutes on days 1-3.
-
Courses 3-6: Beginning 21 days after course 2, patients receive doxorubicin and motexafin gadolinium as in group A.
Treatment in both groups continues for up to 6 courses in the absence of disease progression, unacceptable toxicity, or a cumulative doxorubicin dose of 450 mg/m^2.
Cohorts of 3-6 patients receive escalating doses of doxorubicin and motexafin gadolinium until the maximum tolerated dose (MTD) is determined. The MTD is defined as the highest dose at which no more than 0 of 3 or 1 of 6 patients experience dose-limiting toxicity.
Patients are followed at 1 and 2 months.
PROJECTED ACCRUAL: A total of 3-48 patients will be accrued for this study.
Study Design
Outcome Measures
Primary Outcome Measures
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
-
Histologically confirmed advanced malignancy that is considered incurable
-
Recurrent or metastatic disease
-
Relapsed solid tumors include, but are not limited to the following sites:
-
Lung
-
Breast
-
Colon
-
Prostate
-
Head and neck
-
Hormone receptor status:
-
Not specified
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Sex
- Not specified
Menopausal status
- Not specified
Performance status:
- ECOG 0-2
Life expectancy:
- Not specified
Hematopoietic:
-
Absolute neutrophil count at least 1,500/mm^3
-
Platelet count at least 100,000/mm^3
Hepatic:
-
Bilirubin no greater than 1.5 mg/dL
-
AST and ALT no greater than 2 times upper limit of normal
Renal:
- Creatinine no greater than 2.0 mg/dL
Cardiovascular:
-
LVEF greater than 45% at rest
-
No prior myocardial infarction
-
No congestive heart failure
-
No clinically significant ventricular arrhythmias
Other:
-
No history of HIV infection
-
No history of porphyria
-
No glucose-6-phosphate dehydrogenase deficiency
-
Not pregnant or nursing
-
Negative pregnancy test
-
Fertile patients must use effective contraception during and for at least 6 months after study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
-
At least 28 days since prior chemotherapy
-
No prior lifetime cumulative doxorubicin exposure of more than 300 mg/m^2
-
No other concurrent cytotoxic chemotherapy
Endocrine therapy:
- Not specified
Radiotherapy:
-
At least 28 days since prior radiotherapy
-
No concurrent radiotherapy
Surgery:
- No concurrent surgery
Other:
-
At least 14 days since prior multidrug resistance-modulating drugs (e.g., PSC833 or cyclosporine)
-
No other concurrent antineoplastic or investigational agents
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hillman Cancer Center at University of Pittsburgh Cancer Institute | Pittsburgh | Pennsylvania | United States | 15232 |
| 2 | University of Wisconsin Comprehensive Cancer Center | Madison | Wisconsin | United States | 53792 |
Sponsors and Collaborators
- University of Wisconsin, Madison
- National Cancer Institute (NCI)
Investigators
- Study Chair: Markus Renschler, MD, Pharmacyclics LLC.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CDR0000069322
- P30CA014520
- WCCC-CO-01910
- PCI-PCYC-0207
- NCI-G02-2061