SU5416 and Irinotecan in Treating Patients With Advanced Colorectal Cancer

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

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

Study Overview

• Status: Completed
• Conditions: Stage IV Colon Cancer; Stage IV Rectal Cancer; Recurrent Colon Cancer; Recurrent Rectal Cancer; Adenocarcinoma of the Rectum; Stage III Colon Cancer; Stage III Rectal Cancer; Adenocarcinoma of the Colon
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: irinotecan hydrochloride; Drug: semaxanib

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.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Other: laboratory biomarker analysis; Correlative studies; Drug: irinotecan hydrochloride; Given IV; Other Names: irinotecan; Campto; Camptosar; U-101440E; CPT-11; Drug: semaxanib; Given IV; Other Names: SU5416; semoxind; Sugen 5416

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to disease progression (TTP)	Estimated using the Kaplan-Meier method. Associated 95% confidence intervals will be computed.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall tumor response rate (CR + PR)	Associated 95% confidence intervals.	Up to 3 years
Overall survival	Estimated using the Kaplan-Meier method.	From date of entry on study to the date of death of the patients; assessed up to 3 years
Toxicity graded using the NCI CTC version 2.0		Up to 3 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: James Abbruzzese, M.D. Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start: March 1, 2000
• Primary Completion (Actual): March 1, 2003

Study Registration Dates

• First Submitted: June 2, 2000
• First Submitted That Met QC Criteria: May 2, 2003
• First Posted (Estimate): May 5, 2003

Study Record Updates

• Last Update Posted (Estimate): January 23, 2013
• Last Update Submitted That Met QC Criteria: January 22, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Recurrence; Adenocarcinoma; Rectal Neoplasms; Colonic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: NCI-2012-02330; N01CM17003 (U.S. NIH Grant/Contract); ID-99-243; CDR0000067823 (Registry Identifier: PDQ (Physician Data Query))