Clinical trial NCT00036790: Motexafin Gadolinium and Doxorubicin in Treating Patients With Advanced Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Keywords: 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)
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Hillman Cancer Center at University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
Study officials:
affiliation: Pharmacyclics LLC.
name: Markus Renschler, MD
role: STUDY_CHAIR
References: