Liposomal SN-38 in Treating Patients With Metastatic Colorectal Cancer

Phase II Trial of LE SN38 in Patients With Metastatic Colorectal Cancer After Progression on Oxaliplatin

RATIONALE: Drugs used in chemotherapy, such as liposomal SN-38, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well liposomal SN-38 works in treating patients with metastatic colorectal cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: SN-38 liposome

Detailed Description

OBJECTIVES:

Primary

• Determine the objective response rate following treatment with SN-38 liposome as a second-line treatment in patients with metastatic colorectal cancer.

Secondary

• Determine the toxicity profile of this drug in these patients.
• Determine the proportion of patients treated with this drug who experience any grade 3 or greater toxicity.
• Determine progression-free survival and overall survival for patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive SN-38 liposome IV over 90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for up to 3 years.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92120
      • Kaiser Permanente Medical Office -Vandever Medical Office
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Tunnell Cancer Center at Beebe Medical Center
    • Newark, Delaware, United States, 19713
      • CCOP - Christiana Care Health Services
  • Maryland
    • Elkton MD, Maryland, United States, 21921
      • Union Hospital Cancer Program at Union Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Nevada Cancer Research Foundation
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Cancer Institute of New Jersey at Cooper - Voorhees
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
    • Kinston, North Carolina, United States, 28501
      • Kinston Medical Specialists
  • Ohio
    • Columbus, Ohio, United States, 43210-1240
      • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically determined metastatic colorectal cancer*

  • Primary lesion confirmed endoscopically, surgically, or radiologically NOTE: * Patients with a history of colorectal cancer treated by surgical resection who develop radiological or clinical evidence of metastatic cancer do not require separate histological or cytological confirmation of metastatic disease, unless more than 5 years between primary surgery and development of metastatic disease OR primary cancer was stage I

• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

  • Nonmeasurable lesions include the following:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Lymphangitis cutis/pulmonis
    • Abdominal masses not confirmed and followed by imaging techniques
    • Cystic lesions

• UGT1A1*1 homozygous or UGT1A1*28 heterozygous genotype status

  • Patients with homozygous UGT1A1*28 genotype not eligible
• Received at least 1 prior regimen with oxaliplatin for metastatic disease
• Recurrent disease following prior adjuvant therapy allowed

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Creatinine normal
• Bilirubin normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception duration and for 3 months after completion of study treatment
• No known Gilbert's disease or other chronic liver disease
• No colonic or small bowel disorders (e.g., inflammatory bowel disease, Crohn's disease, or ulcerative colitis) that predispose the patients to uncontrolled diarrhea (i.e., > 3 watery or soft stools daily at baseline in patients without a colostomy or ileostomy)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy
• No prior irinotecan
• Prior pelvic radiotherapy allowed as long as measurable lesion is outside irradiated field
• No concurrent palliative radiotherapy
• No other concurrent chemotherapy
• No concurrent steroids except those given for adrenal failure, hormones for non-disease-related conditions (e.g., insulin for diabetes), or intermittent dexamethasone as an antiemetic or for prevention of infusion reaction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SN-38 liposome; Patients receive SN-38 liposome IV over 90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for up to 3 years.	Drug: SN-38 liposome; 38 mg/sq m IV infusion over 30 min q 21 days (1 cycle) until progression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective response rate	q 2 cycles during tx

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	3 years
Progression-free survival	3 years
Toxicity	q cycle during tx

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Allyson Ocean, MD, Weill Medical College of Cornell University

Publications and helpful links

General Publications

• Ocean AJ, Niedzwiecki D, Atkins JN, et al.: LE-SN38 for metastatic colorectal cancer after progression on oxaliplatin: results of CALGB 80402. [Abstract] J Clin Oncol 26 (Suppl 15): A-4109, 2008.

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (ACTUAL): January 1, 2007
• Study Completion (ACTUAL): June 1, 2010

Study Registration Dates

• First Submitted: April 5, 2006
• First Submitted That Met QC Criteria: April 5, 2006
• First Posted (ESTIMATE): April 6, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): June 29, 2016
• Last Update Submitted That Met QC Criteria: June 28, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; recurrent colon cancer; recurrent rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: CALGB-80402; U10CA031946 (U.S. NIH Grant/Contract); CDR0000467234 (REGISTRY: NCI Physician Data Query)