An Open-Label Phase I Dose Escalation Trial To Evaluate The Safety And Pharmacokinetics Of Motexafin Gadolinium And Doxorubicin Chemotherapy In The Treatment Of Advanced Malignancies
18 Years
N/A
Both
Breast Cancer, Chronic Myeloproliferative Disorders, Colorectal Cancer, Head and Neck Cancer, Leukemia, Lung Cancer, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic/Myeloproliferative Diseases, Prostate Cancer, Small Intestine Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
An Open-Label Phase I Dose Escalation Trial To Evaluate The Safety And Pharmacokinetics Of Motexafin Gadolinium And Doxorubicin Chemotherapy In The Treatment Of Advanced Malignancies
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Markus Renschler, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Pharmacyclics
Authority:
United States: Federal Government
Study ID:
CDR0000069322
NCT ID:
NCT00036790
Start Date:
February 2002
Completion Date:
Related Keywords:
- Breast Cancer
- Chronic Myeloproliferative Disorders
- Colorectal Cancer
- Head and Neck Cancer
- Leukemia
- Lung Cancer
- Lymphoma
- Multiple Myeloma and Plasma Cell Neoplasm
- Myelodysplastic/Myeloproliferative Diseases
- Prostate Cancer
- Small Intestine Cancer
- Unspecified Adult Solid Tumor, Protocol Specific
- stage III adult Hodgkin lymphoma
- stage IV adult Hodgkin lymphoma
- recurrent adult Hodgkin lymphoma
- stage III cutaneous T-cell non-Hodgkin lymphoma
- stage IV cutaneous T-cell non-Hodgkin lymphoma
- recurrent cutaneous T-cell non-Hodgkin lymphoma
- isolated plasmacytoma of bone
- extramedullary plasmacytoma
- refractory multiple myeloma
- Waldenstrom macroglobulinemia
- stage III multiple myeloma
- stage III chronic lymphocytic leukemia
- stage IV chronic lymphocytic leukemia
- recurrent adult acute myeloid leukemia
- recurrent adult acute lymphoblastic leukemia
- relapsing chronic myelogenous leukemia
- refractory chronic lymphocytic leukemia
- small intestine lymphoma
- unspecified adult solid tumor, protocol specific
- chronic phase chronic myelogenous leukemia
- accelerated phase chronic myelogenous leukemia
- blastic phase chronic myelogenous leukemia
- meningeal chronic myelogenous leukemia
- untreated adult acute lymphoblastic leukemia
- untreated adult acute myeloid leukemia
- refractory hairy cell leukemia
- chronic myelomonocytic leukemia
- T-cell large granular lymphocyte leukemia
- acute undifferentiated leukemia
- stage III grade 1 follicular lymphoma
- stage III grade 2 follicular lymphoma
- stage III grade 3 follicular lymphoma
- stage III adult diffuse small cleaved cell lymphoma
- stage III adult diffuse mixed cell lymphoma
- stage III adult diffuse large cell lymphoma
- stage III adult immunoblastic large cell lymphoma
- stage III adult lymphoblastic lymphoma
- stage III adult Burkitt lymphoma
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage IV grade 3 follicular lymphoma
- stage IV adult diffuse small cleaved cell lymphoma
- stage IV adult diffuse mixed cell lymphoma
- stage IV adult diffuse large cell lymphoma
- stage IV adult immunoblastic large cell lymphoma
- stage IV adult lymphoblastic lymphoma
- stage IV adult Burkitt lymphoma
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent adult Burkitt lymphoma
- stage III adult T-cell leukemia/lymphoma
- stage IV adult T-cell leukemia/lymphoma
- recurrent adult T-cell leukemia/lymphoma
- secondary acute myeloid leukemia
- prolymphocytic leukemia
- stage III mantle cell lymphoma
- stage IV mantle cell lymphoma
- recurrent mantle cell lymphoma
- angioimmunoblastic T-cell lymphoma
- anaplastic large cell lymphoma
- stage III mycosis fungoides/Sezary syndrome
- stage IV mycosis fungoides/Sezary syndrome
- recurrent mycosis fungoides/Sezary syndrome
- chronic eosinophilic leukemia
- chronic neutrophilic leukemia
- recurrent non-small cell lung cancer
- recurrent small cell lung cancer
- stage IIIA non-small cell lung cancer
- stage IIIB non-small cell lung cancer
- stage IV non-small cell lung cancer
- extensive stage small cell lung cancer
- limited stage small cell lung cancer
- recurrent breast cancer
- stage IIIA breast cancer
- stage IIIB breast cancer
- stage IIIC breast cancer
- stage IV breast cancer
- recurrent colon cancer
- stage III colon cancer
- stage IV colon cancer
- recurrent prostate cancer
- stage III prostate cancer
- stage IV prostate cancer
- recurrent lip and oral cavity cancer
- stage III lip and oral cavity cancer
- stage IV lip and oral cavity cancer
- recurrent paranasal sinus and nasal cavity cancer
- stage III paranasal sinus and nasal cavity cancer
- stage IV paranasal sinus and nasal cavity cancer
- recurrent metastatic squamous neck cancer with occult primary
- recurrent hypopharyngeal cancer
- stage III hypopharyngeal cancer
- stage IV hypopharyngeal cancer
- recurrent laryngeal cancer
- stage III laryngeal cancer
- stage IV laryngeal cancer
- recurrent oropharyngeal cancer
- stage III oropharyngeal cancer
- stage IV oropharyngeal cancer
- recurrent nasopharyngeal cancer
- stage III nasopharyngeal cancer
- stage IV nasopharyngeal cancer
- atypical chronic myeloid leukemia
- myelodysplastic/myeloproliferative disease, unclassifiable
- recurrent marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- stage III small lymphocytic lymphoma
- stage III marginal zone lymphoma
- stage IV small lymphocytic lymphoma
- stage IV marginal zone lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- splenic marginal zone lymphoma
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- Breast Neoplasms
- Neoplasms
- Colorectal Neoplasms
- Head and Neck Neoplasms
- Leukemia
- Lung Neoplasms
- Lymphoma
- Lymphoma, Non-Hodgkin
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Myeloproliferative Disorders
- Prostatic Neoplasms
- Lymphoma, Large-Cell, Immunoblastic
- Duodenal Neoplasms
- Ileal Neoplasms
- Jejunal Neoplasms
- Intestinal Neoplasms
- Myelodysplastic-Myeloproliferative Diseases
Name | Location |
|---|---|
| University of Wisconsin Comprehensive Cancer Center | Madison, Wisconsin 53792 |
| Hillman Cancer Center at University of Pittsburgh Cancer Institute | Pittsburgh, Pennsylvania 15236 |
