Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

ZD0473 and Doxorubicin in Treating Patients With Advanced Solid Tumors or Lymphoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over NCI MSKCC-00044 NCI-G01-1942, NCT00016172

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.

Entry 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

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

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

Expected Enrollment

Approximately 24 patients will be accrued for this study.

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.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

David R. Spriggs, MD, Protocol chair		Ph: 212-639-2203; 800-525-2225

Registry Information
Official Title		A Phase I Study of ZD0473 and Doxil in Patients with Advanced Refractory Cancer
Trial Start Date		2000-11-13
Registered in ClinicalTrials.gov		NCT00016172
Date Submitted to PDQ		2001-03-13
Information Last Verified		2002-04-01
NCI Grant/Contract Number		P30-CA08748