Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	MSKCC-94106 NCI-T94-0126D, T94-0126

Objectives

I.  Evaluate the efficacy of aminocamptothecin (9-AC) in patients with 
fluorouracil-resistant colorectal cancer.

II.  Describe the acute and chronic toxicities associated with this treatment.

III.  Compare pharmacokinetic data from this study with previously obtained 
pharmacokinetic data for 9-AC given as a 72-hour infusion.

IV.  Correlate the response and toxicities of 9-AC with peak concentrations, 
steady-state levels, and/or area under the curve of total drug or lactone 
plasma concentrations.

V.  Correlate pre- and post-treatment tissue levels of topoisomerase in biopsy 
specimens from consenting patients with sensitivity or resistance to 9-AC.

Entry Criteria

Disease Characteristics:

Histologically diagnosed, metastatic colorectal cancer not curable by surgery,
radiotherapy, or standard chemotherapy
  Confirmation of pathology by MSKCC required

Bidimensionally measurable disease outside any prior radiotherapy field
required

Disease progression despite 1 prior fluorouracil (5-FU) regimen required,
i.e.:
  During or within 6 months of completing adjuvant 5-FU

  During an additional 5-FU regimen for metastatic disease following a
  disease-free interval greater than 6 months after adjuvant 5-FU

No CNS metastases

No carcinomatous meningitis

Prior/Concurrent Therapy:

Biologic therapy:
  Not specified

Chemotherapy:
  At least 4 weeks since myelosuppressive chemotherapy and recovered
  No more than 1 prior chemotherapy regimen except 5-FU in the adjuvant and
  metastatic setting
     5-FU given on 2 different schedules counts as 2 treatment regimens
  No prior aminocamptothecin or other camptothecins

Endocrine therapy:
  Not specified

Radiotherapy:
  At least 4 weeks since radiotherapy to major bone marrow sites

Surgery:
  Not specified

Patient Characteristics:

Age:
  18 and over

Performance status:
  Karnofsky 70-100%

Hematopoietic:
  WBC at least 4,000
  AGC at least 1,500
  Platelets at least 150,000

Hepatic:
  Bilirubin no greater than 1.5 mg/dl
  SGOT less than 5 x ULN

Renal:
  Creatinine no greater than 1.5 mg/dl

Cardiovascular:
  No MI within the past 6 months
  No current or prior NYHA class III/IV status

Other:
  No active uncontrolled infection
  No medical or psychiatric condition incompatible with study
  No history of second malignancy except curatively treated:
     Basal cell carcinoma
     Cervical carcinoma in situ
  No pregnant or nursing women
  Effective contraception required of fertile patients

Blood/body fluid analyses and physical exams to determine eligibility
completed within 14 days prior to registration; imaging studies and other
screening exams completed within 21 days prior to registration

Expected Enrollment

Up to 30 patients will be entered over 1 year.  If no CR or PR occurs in the 
first 14 patients, the study will close.

Outline

Single-Agent Chemotherapy.  Aminocamptothecin, 9-AC, NSC-603071.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Leonard Saltz, MD, Protocol chair		Ph: 212-639-2501; 800-525-2225