Colorectal Cancer
Conditions
Keywords
stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer
Brief summary
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.
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.
Interventions
DRUGthalidomide
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).
PROCEDUREadjuvant 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.
OTHERPlacebo
oral placebo once daily
Sponsors
National Cancer Institute (NCI)
National Institutes of Health Clinical Center (CC)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression | 62 months | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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). | 23 |
| Arm 2 - Placebo Once Daily Patients receive oral placebo once daily. | 16 |
| Total | 39 |
Baseline characteristics
| Characteristic | Arm 1 - Thalidomide Once Daily | Arm 2 - Placebo Once Daily | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 9 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 7 Participants | 19 Participants |
| Age, Continuous | 64.89 years STANDARD_DEVIATION 8.7 | 71.19 years STANDARD_DEVIATION 11.76 | 67.47 years STANDARD_DEVIATION 10.54 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 16 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 17 Participants | 13 Participants | 30 Participants |
| Region of Enrollment United States | 23 participants | 16 participants | 39 participants |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Male | 15 Participants | 9 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 23 | 6 / 16 |
| serious Total, serious adverse events | 5 / 23 | 4 / 16 |
Outcome results
Primary
Time to Progression
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
Time frame: 62 months
Population: The analysis was not done because there were not enough subjects to do any of the statistical analyses.