Clinical trial NCT00016172: ZD0473 and Doxorubicin in Treating Patients With Advanced Solid Tumors or Lymphoma
Official title: A Phase I Study of ZD0473 and Doxil in Patients With Advanced Refractory Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma
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
small intestine lymphoma
unspecified adult solid tumor, protocol specific
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
primary central nervous system non-Hodgkin lymphoma
AIDS-related peripheral/systemic lymphoma
AIDS-related primary CNS lymphoma
intraocular lymphoma
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
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
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-02-16
Sex: ALL
Minimum age (years): 18
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. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of combining ZD0473 and doxorubicin in treating patients who have advanced solid tumors or lymphoma.

Detailed description: OBJECTIVES: I. Determine the maximum tolerated dose of ZD0473 and doxorubicin HCl liposome in patients with advanced or metastatic solid tumors or lymphoma. II. Determine the qualitative and quantitative toxic effects of this regimen in this patient population. III. Determine the pharmacokinetics of these drugs in this patient population. IV. Determine the antitumor activity of this regimen in this patient population.

OUTLINE: This is a dose-escalation study. Patients receive doxorubicin HCl liposome IV over 60 minutes followed by ZD0473 IV over 60 minutes on day 1. Treatment repeats every 28 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. Patients with partial response (PR) or complete response (CR) may continue treatment until disease progression or until 2 courses after maximum response. Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome and ZD0473 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity. Patients are followed at 4 weeks and 3 months. Patients with PR or CR ongoing continue follow-up every 3 months until relapse.

PROJECTED ACCRUAL: Approximately 24 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically confirmed advanced or metastatic solid tumors or lymphoma Refractory to standard curative therapy OR No curative therapy exists Serologically, clinically, and/or radiographically assessable disease No newly diagnosed brain metastases Intracranial disease that is stable for at least 6 months allowed

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Absolute granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than upper limit of normal (ULN) AST or ALT no greater than 2.0 times ULN Alkaline phosphatase no greater than 2.0 times ULN Renal: Creatinine no greater than ULN Creatinine clearance at least 60 mL/min Cardiovascular: Ejection fraction at least 50% Other: No underlying medical condition that would preclude study or that is uncontrolled No active serious infection No neurotoxicity or preexisting grade 3 or higher neuropathy Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 5 days since prior immunotherapy Chemotherapy: At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas and similar compounds) No more than 3 prior chemotherapy regimens for metastatic disease No prior anthracycline exposure exceeding 300 mg/m2 doxorubicin No prior doxorubicin HCl liposome Endocrine therapy: At least 5 days since prior hormonal therapy Radiotherapy: At least 3 weeks since prior radiotherapy and recovered No prior radiotherapy to more than 30% of functioning bone marrow Surgery: At least 3 weeks since prior major surgery Other: No other concurrent experimental drugs No other concurrent anticancer therapy

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: David R. Spriggs, MD
role: STUDY_CHAIR
References: