SU5416 and Irinotecan in Treating Patients With Advanced Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00005818
First received: June 2, 2000
Last updated: January 22, 2013
Last verified: January 2013
  Purpose

Phase I/II trial to study the effectiveness of combining SU5416 and irinotecan in treating patients who have advanced colorectal cancer. SU5416 may stop the growth of colorectal cancer by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die


Condition Intervention Phase
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
Drug: irinotecan hydrochloride
Drug: semaxanib
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Escalating Doses of SU5416 (NSC 696819) in Combination With CPT-11 in Patients With Advanced Colorectal Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Time to disease progression (TTP) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method. Associated 95% confidence intervals will be computed.


Secondary Outcome Measures:
  • Overall tumor response rate (CR + PR) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Associated 95% confidence intervals.

  • Overall survival [ Time Frame: From date of entry on study to the date of death of the patients; assessed up to 3 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.

  • Toxicity graded using the NCI CTC version 2.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 68
Study Start Date: March 2000
Primary Completion Date: March 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (irinotecan hydrochloride, semaxanib)
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.
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Drug: semaxanib
Given IV
Other Names:
  • semoxind
  • SU5416
  • Sugen 5416
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005818

Locations
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: James Abbruzzese M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005818     History of Changes
Other Study ID Numbers: NCI-2012-02330, ID-99-243, N01CM17003, CDR0000067823
Study First Received: June 2, 2000
Last Updated: January 22, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Rectal Neoplasms
Colonic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Irinotecan
Camptothecin
Semaxinib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors

ClinicalTrials.gov processed this record on October 19, 2014