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
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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
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 Adjuvants, Immunologic Thalidomide |
Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Immunosuppressive Agents 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 May 19, 2013