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A Phase I/II Study of Escalating Doses of SU5416 (NSC 696819) in Combination With CPT-11 in Patients With Advanced Colorectal Carcinoma


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum, Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage III Colon Cancer, Stage III Rectal Cancer, Stage IV Colon Cancer, Stage IV Rectal Cancer

Thank you

Trial Information

A Phase I/II Study of Escalating Doses of SU5416 (NSC 696819) in Combination With CPT-11 in Patients With Advanced Colorectal Carcinoma


OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) and dose-limiting toxicity of SU5416 in
combination with irinotecan in patients with advanced colorectal cancer.

II. Determine time to disease progression, objective response rate, and survival time in
these patients receiving this regimen at the MTD.

III. Evaluate the safety and tolerance of this regimen in these patients.

OUTLINE: This is a dose-escalation study of SU5416.

Patients receive irinotecan IV over 90 minutes on day 1 of weeks 1-4 and SU5416 IV over 60
minutes on days 1 and 4 of weeks 1-6. Treatment continues every 6 weeks in the absence of
unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of SU5416 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of
6 patients experience dose-limiting toxicity. Once the MTD is determined, additional
patients are accrued to receive treatment with SU5416 and irinotecan at the recommended
phase II dose.

Patients are followed every 3 months.


Inclusion Criteria:



- Patients must have histologically confirmed adenocarcinoma of the colon or rectum

- Patients must have locally advanced or metastatic disease not amendable to
potentially curative treatment

- Patients must have an ECOG performance status of 0-2

- Men and women of any racial and ethnic group

- Absolute neutrophil count (neutrophils + bands) of >= 1,500/ul

- Platelet count of >= 100,000/ul

- Patients must have a serum creatinine of =< 1.5 mg/dL or a calculated creatinine
clearance >= 60 mL/min

- Serum bilirubin =< 1.5 mg/dL, regardless of whether patients have liver involvement
secondary to tumor

- SGOT must be =< 3 times institutional upper limit of normal

- Patients must be fully recovered from any previous surgery (at least 4 weeks from
major surgery)

- Patients must have recovered from prior radiation therapy (at least 4 weeks from
radiation)

- Fertile patients (male and female) must agree to use a medically effective
contraceptive method throughout the treatment period and for 3 months following
cessation of treatment

- Patients must provide written informed consent

- Patients must have either measurable or evaluable disease; measurable disease is
defined as at least one bidimensionally measurable lesion >= 1 x 1 cm that is outside
the field of any prior radiation therapy

- In Phase I: Patients with a history of a prior malignancy are eligible for treatment

- In Phase II: Patients who have undergone potentially curative therapy for a prior
malignancy and who have had no evidence of that disease for > 5 years are eligible
for treatment; adequately treated basal cell or squamous cell skin cancer does not
apply

- In the Phase I portion of the study the following eligibility criteria must be met:

- Patients must have received no more than two prior chemotherapy regimens (one of
which must have contained a fluorinated pyrimidine) for locally advanced or
metastatic disease; if a patient progressed while on or within 6 months of
adjuvant therapy, the adjuvant regimen will be considered as treatment for
metastatic disease

- In the Phase II portion of the study the following eligibility criteria must be met:

- Patients must have received one and only one prior chemotherapy regimen, which
must have contained a fluorinated pyrimidine, for treatment of locally advanced
or metastatic disease; if a patient progressed while on or within 6 months of
adjuvant therapy, the adjuvant regimen will be considered as treatment for
metastatic disease

Exclusion Criteria:

- Patients who have previously received SU5416, CPT-11, or any topoisomerase I
inhibitor

- Patients with uncompensated coronary artery disease on electrocardiogram or physical
examination, or with a history of myocardial infarction, or severe/unstable angina in
the past 6 months are not eligible

- Patients with diabetes mellitus with severe peripheral vascular disease and patients
who have had a deep venous or arterial thrombosis (including pulmonary embolism)
within 3 months of entry are not eligible

- Patients with known allergy to Cremaphor, or Cremophor-based drug products

- Patients with any active or uncontrolled infection

- Patients with psychiatric disorders that would interfere with consent or follow-up

- CPT-11 is known to have teratogenic potential and may be excreted in milk; the
current SU5416 Investigator's Brocure indicates that teratogenicity studies have not
yet been performed; however, other antiangiogenesis drugs, such as thalidomide, are
known to have teratogenic potential; based on the available data, there is potential
for significant risk to a developing fetus or breast-feeding child; therefore,
pregnant women, women who are breast-feeding, and fertile men and women, unless
utilizing birth control are excluded from this study; a negative pregnancy test must
be documented during the screening period for women of childbearing potential

- Patients with either a prior history of or clinically apparent central nervous system
metastases or leptomeningeal carcinomatosis disease

- Patients with a history of seizures or who are receiving phenytoin, phenobarbital, or
other antipileptic prophylaxis

- Patients with uncontrolled diabetes mellitus

- Patients with known Gilbert's Disease (may have excessive CPT-11-induced toxicity)

- Patients with any other severe concurrent disease which in the judgement of the
investigator would make the patient inappropriate for the study

- Patients who have received any investigational drug =< 30 days prior to enrollment

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Time to disease progression (TTP)

Outcome Description:

Estimated using the Kaplan-Meier method. Associated 95% confidence intervals will be computed.

Outcome Time Frame:

6 months

Safety Issue:

No

Principal Investigator

James Abbruzzese

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02330

NCT ID:

NCT00005818

Start Date:

March 2000

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Colon
  • Adenocarcinoma of the Rectum
  • Recurrent Colon Cancer
  • Recurrent Rectal Cancer
  • Stage III Colon Cancer
  • Stage III Rectal Cancer
  • Stage IV Colon Cancer
  • Stage IV Rectal Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Colonic Neoplasms
  • Rectal Neoplasms
  • Colorectal Neoplasms

Name

Location

M D Anderson Cancer CenterHouston, Texas  77030