Know Cancer

or
forgot password

A Phase II, Open-Label, Multicenter Study of the GARFT Inhibitor AG2037 in Patients With Metastatic Colorectal Cancer Who Failed Treatment With a 5-Fluorouracil/Leucovorin Regimen


Phase 2
18 Years
N/A
Not Enrolling
Both
Colorectal Cancer

Thank you

Trial Information

A Phase II, Open-Label, Multicenter Study of the GARFT Inhibitor AG2037 in Patients With Metastatic Colorectal Cancer Who Failed Treatment With a 5-Fluorouracil/Leucovorin Regimen


OBJECTIVES:

Primary

- Determine the overall objective response rate (complete and partial response) in
patients with metastatic adenocarcinoma of the colon or rectum that failed prior
fluorouracil and leucovorin calcium therapy and up to 1 other chemotherapy regimen (not
including adjuvant chemotherapy) when treated with AG2037.

Secondary

- Determine time to progression in patients treated with this drug.

- Determine the safety of this drug in these patients.

- Determine the 1-year and overall survival of patients treated with this drug.

- Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.

- Determine changes in patient outcomes (e.g., symptoms, functioning, and quality of
life) in patients treated with this drug.

- Correlate various genetic markers of methylthioadenosine phosphorylase (MTAP), folate,
and purine metabolism with clinical response in patients treated with this drug.

OUTLINE: This is an open-label, multicenter study.

Patients receive AG2037 IV over 15-30 minutes on days 1, 8, and 15. Courses repeat every 28
days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, on day 1 of every course (beginning with course 2),
upon exit from the study, and then 30 days after the last treatment dose.

Patients are followed every 3 months for up to 1 year.

PROJECTED ACCRUAL: A total of 23-56 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or
rectum

- Stage IV or recurrent disease

- Measurable disease

- Disease progression or recurrence during or after completion of prior first-line
chemotherapy with fluorouracil and leucovorin calcium (5-FU/LV)

- Prior irinotecan or oxaliplatin as part of the 5-FU/LV regimen or as subsequent
therapy allowed

- Only 2 prior regimens for metastatic disease allowed

- One additional regimen as adjuvant therapy allowed provided patient remained
disease-free for > 6 months after completion of therapy*

- Newer, targeted investigational agents (e.g., cetuximab or bevacizumab) are not
counted as a chemotherapeutic regimen unless used in combination with a
cytotoxic regimen NOTE: *If evidence of failure occurred within < 6 months after
completion of adjuvant therapy, patients may have received only 1 additional
regimen for metastatic disease

- No active brain metastases (requiring treatment or progressing)

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- More than 12 weeks

Hematopoietic

- Absolute granulocyte count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9 g/dL

Hepatic

- AST and ALT ≤ 2 times upper limit of normal (ULN) (5 times ULN if liver involvement
is present)

- Bilirubin ≤ 1.5 mg/dL (3.0 mg/dL for patients with Gilbert's syndrome)

Renal

- Creatinine ≤ 1.5 mg/dL

- Creatinine clearance ≥ 60 mL/min

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 1 month after study
participation

- No concurrent unstable or severe medical condition that would preclude study
participation

- No psychological or sociological condition, addictive disorder, or family problem
that would preclude study compliance

- No other malignancy within the past 5 years except curatively treated nonmelanoma
skin cancer or carcinoma in situ of the cervix or breast

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Disease Characteristics

- More than 14 days since prior blood transfusion

Chemotherapy

- See Disease Characteristics

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
and recovered

Endocrine therapy

- Not specified

Radiotherapy

- More than 4 weeks since prior radiotherapy and recovered

- No prior radiotherapy to > 40% of bone marrow space

Surgery

- Not specified

Other

- No prior glycinamide ribonucleotide formyltransferase (GARFT) inhibitors

- More than 28 days since prior investigational agent and recovered

- No concurrent allopurinol

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Leonard B. Saltz, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000370828

NCT ID:

NCT00085592

Start Date:

March 2004

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • recurrent colon cancer
  • stage IV colon cancer
  • recurrent rectal cancer
  • stage IV rectal cancer
  • adenocarcinoma of the colon
  • adenocarcinoma of the rectum
  • Colonic Neoplasms
  • Colorectal Neoplasms

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve UniversityCleveland, Ohio  44106
Lombardi Cancer Center at Georgetown University Medical CenterWashington, District of Columbia  20007
H. Lee Moffitt Cancer Center and Research Institute at University of South FloridaTampa, Florida  33612
Southwest Cancer Care - PowayPoway, California  92064