Surgery With or Without Thalidomide in Treating Patients With Recurrent or Metastatic Colorectal Cancer

This study has been terminated.
(DSMB recommended closure of the protocol due to slow accrual.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Steven Rosenberg, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00019747
First received: July 11, 2001
Last updated: November 7, 2012
Last verified: November 2012
  Purpose

RATIONALE: Thalidomide may stop the growth of colorectal cancer by stopping blood flow to the tumor. Giving thalidomide after surgery may kill any remaining tumor cells.

PURPOSE: This randomized phase II trial is studying surgery and thalidomide to see how well they work compared to surgery alone in treating patients with recurrent or metastatic colorectal cancer.


Condition Intervention Phase
Colorectal Cancer
Drug: thalidomide
Procedure: adjuvant therapy
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Oral Thalidomide as an Adjuvant Agent Following Metastasectomy in Patients With Recurrent Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Time to Progression [ Time Frame: 62 months ] [ Designated as safety issue: No ]
    Time to progression was measured from the on study date until the date of progression or last follow up. Progression was assessed by the Response Evaluation Criteria for Solid Tumors (RECIST).Progressive Disease (PD)is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions


Enrollment: 39
Study Start Date: August 1999
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 - Thalidomide once daily
Patients receive oral thalidomide 100 mg at bedtime once daily for 4 weeks, then progresses to 200 mg at bedtime for 4 weeks, then progresses to 300 mg at bedtime (maintenance dose).
Drug: thalidomide
oral thalidomide 100 mg at bedtime once daily for 4 weeks, then progresses to 200 mg at bedtime for 4 weeks, then progresses to 300 mg at bedtime (maintenance dose).
Other Name: Thalomid
Procedure: adjuvant therapy
Initial dose: 100 mg by mouth (po) every bedtime ( Q hs) for four weeks, then progress to 200 mg po Q hs for four weeks, then progress to maintenance dose: 300 mg po Q hs.
Placebo Comparator: Arm 2 - Placebo once daily
Patients receive oral placebo once daily.
Procedure: adjuvant therapy
Initial dose: 100 mg by mouth (po) every bedtime ( Q hs) for four weeks, then progress to 200 mg po Q hs for four weeks, then progress to maintenance dose: 300 mg po Q hs.
Other: Placebo
oral placebo once daily

Detailed Description:

OBJECTIVES:

  • Compare the disease-free survival probability in patients with previously resected recurrent or metastatic colorectal carcinoma treated with adjuvant thalidomide vs placebo.
  • Compare the time to recurrence in patients treated with these regimens.
  • Determine whether serum/plasma levels of vascular endothelial growth factor and basic fibroblast growth factor preresection and postresection correlate with tumor recurrence and determine if these levels, as well as carcinoembryonic antigen (CEA) measurements, aid in predicting time to recurrence in these patients.
  • Determine the pharmacokinetics and toxicity of long-term thalidomide therapy in these patients.
  • Determine whether patients receiving thalidomide develop measurable antiangiogenic activity.
  • Measure the presence of circulating tumor cells preresection and postresection and determine if this type of analysis can be used to predict recurrence in this patient population.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to site of most recent lesion resection that rendered no evidence of disease (lung vs liver with no more than 3 lesions vs liver with more than 3 lesions vs lung and liver vs all other sites[including sites that were both resected and ablated]). Patients without evidence of residual disease are randomized to one of two treatment arms.

  • Arm I: Patients receive oral thalidomide once daily.
  • Arm II: Patients receive an oral placebo once daily. Treatment continues in both arms for 2 years in the absence of unacceptable toxicity or disease progression.

Patients are followed every 3 months for up to 3 years.

PROJECTED ACCRUAL: A total of 94 patients (47 per treatment arm) will be accrued for this study within 3 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Diagnosis of recurrent or metastatic colorectal carcinoma previously resected within 12 weeks of study entry

    • Surgical resection combined with radiofrequency ablation allowed

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Hemoglobin at least 8.0 g/dL
  • Absolute neutrophil count at least 1,000/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

  • Partial thromboplastin time (PTT)/prothrombin time (PT) no greater than 120% of control (except in therapeutically anticoagulated nonrelated medical conditions [e.g., atrial fibrillation])
  • Total bilirubin no greater than 2.0 mg/dL (direct bilirubin no greater than 1.0 mg/dL for patients with Gilbert's syndrome)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than 2.5 times normal
  • No history of hepatic cirrhosis
  • No concurrent hepatic dysfunction

Renal:

  • Creatinine no greater than 2.0 mg/dL

Cardiovascular:

  • No severe congestive heart failure or active ischemic heart disease
  • No active clots within 1 year before diagnosis OR must be receiving concurrent treatment with anticoagulant (e.g., low molecular weight heparin or equivalent agent)

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use 1 highly effective method of contraception AND 1 additional effective method of contraception for least 4 weeks before, during, and for at least 4 weeks after study participation
  • No history of severe hypothyroidism
  • No history of seizures
  • No significant history of other medical problems that would preclude surgery
  • No peripheral neuropathy greater than grade 1, except localized neuropathy due to a mechanical cause or trauma

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 4 weeks since prior biologic therapy

Chemotherapy:

  • At least 4 weeks since prior chemotherapy

Endocrine therapy:

  • Not specified

Radiotherapy:

  • At least 4 weeks since prior radiotherapy

Surgery:

  • See Disease Characteristics

Other:

  • See Cardiovascular
  • No concurrent sedating drugs that cannot be reduced to a minimal level
  • No concurrent sedating recreational drugs or alcohol
  • No concurrent antiseizure medications
  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: NCT00019747

Locations
United States, Indiana
Center for Cancer Care at Goshen Health System
Goshen, Indiana, United States, 46526
United States, Maryland
Suburban Hospital Cancer Program
Bethesda, Maryland, United States, 20817
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
United States, North Carolina
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
United States, Ohio
Charles M. Barrett Cancer Center at University Hospital
Cincinnati, Ohio, United States, 45267-0558
United States, Pennsylvania
UPMC Cancer Center at UPMC Presbyterian
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Investigators
Study Chair: Steven K. Libutti, MD NCI - Surgery Branch
  More Information

Additional Information:
No publications provided

Responsible Party: Steven Rosenberg, Dr. Steven Rosenberg, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00019747     History of Changes
Other Study ID Numbers: 990102, 99-C-0102, CDR0000067098
Study First Received: July 11, 2001
Results First Received: September 25, 2012
Last Updated: November 7, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Thalidomide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 18, 2014