CC-4047 in Treating Patients With Advanced Solid Tumors That Did Not Respond to Treatment

Study Overview
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Brief Summary
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RATIONALE: CC-4047 may stop the growth of tumor cells by blocking blood flow to the tumor. PURPOSE: This phase I trial is studying the side effects and best dose of CC-4047 in treating patients with advanced solid tumors that did not respond to treatment.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose of CC-4047 in patients with advanced refractory solid tumors. Secondary Assess the safety of this drug in these patients. Assess the antitumor activity of this drug in these patients. Determine the effect of this drug on fetal hemoglobin levels in these patients. OUTLINE: This is a open-label, uncontrolled, nonrandomized, dose-escalation, multicenter study. Treatment phase (course 1): Patients receive oral CC-4047 once daily on days 1-21 followed by a 7-day recovery period. Cohorts of 3-6 patients receive escalating doses of CC-4047 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 (DLT). Patients with no clinical evidence of progressive disease or DLT after course 1 continue study treatment during the extension phase. Patients who develop a DLT during course 1 may continue study treatment at the discretion of the investigator. Extension phase: Patients continue taking CC-4047 at their assigned cohort dose as in course 1. Patients who tolerate a treatment-phase dose higher than the MTD continue treatment at the MTD. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients undergo blood collection at baseline and periodically during study to evaluate fetal hemoglobin levels. After completion of study treatment, patients are followed at 28 days.

Official Title
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A Phase I, Open-Label Study to Determine the Maximum Tolerated Dose (MTD) and to Evaluate the Safety Profile of CC-4047 in Subjects With Advanced Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: CC-4047


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed advanced solid tumor Refractory disease Patients must have been offered and refused OR received and failed prior treatment with all standard or approved therapies for the malignancy Measurable or evaluable disease as confirmed by radiographic or clinical evidence No curative therapy available PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy ≥ 3 months ANC > 1,500/mm³ Platelet count > 75,000/mm³ Hemoglobin ≥ 9.0 g/dL Creatinine ≤ 2.0 mg/dL AST and ALT < 3 times upper limit of normal Not pregnant No nursing during and for ≥ 28 days after completion of study treatment Two negative pregnancy tests required Fertile women must use effective double-method contraception for ≥ 28 days before, during, and for ≥ 28 days after completion of study treatment Men must use a latex condom during sexual contact with fertile females during and for ≥ 28 days after completion of study treatment, even if a prior successful vasectomy was performed Stable neurological exam No serious medical condition or psychiatric illness that would preclude study participation No prior desquamating rash or allergic reaction ≥ grade 2 while taking thalidomide, lenalidomide, or structurally related compounds No peripheral neuropathy ≥ grade 2 No active infection No uncontrolled hyper- or hypocalcemia, glycosemia, or thyroidism PRIOR CONCURRENT THERAPY: No prior CC-4047 More than 28 days since prior cytotoxic chemotherapy (42 days for nitrosoureas) At least 14 days since prior therapeutic radiotherapy More than 14 days since prior thalidomide, lenalidomide, or structurally related compounds More than 14 days since prior biological response modifier therapy Concurrent radiotherapy to treat pain associated with existing bone lesions during the extension phase of the study allowed provided < 10% of bone marrow is irradiated Concurrent systemic steroids for control of CNS primary tumor and/or metastases symptoms allowed provided dose is stable or decreasing AND patient is also taking low-dose aspirin and/or other platelet-active, anti-thrombotic medication during and for 30 days after completion of study treatment No other concurrent chemotherapy or immunotherapy No other concurrent investigational agents No concurrent hematopoietic growth factors during the treatment phase of the study No other concurrent anticancer agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CC-4047<br> | Drug: CC-4047<br>* Oral CC-4047 once daily on days 1-21 followed by a 7-day recovery period. Cohorts of 3-6 patients receive escalating doses of CC-4047 until the maximum tolerated dose (MTD) is determined.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose | To determine the maximum tolerated dose (MTD) of daily CC-4047 in an initial 28-day cycle (21 days of CC-4047 followed by 7 days of no therapy) in subjects with advanced solid tumors (Cohort A). | after initial 28 day cycle | 
| Dose-limiting toxicity |  | Courses repeat every 28 days for up to 24 months in the absence of unacceptable toxicity. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response as assessed by RECIST criteria |  | after every 2 courses (28 days/ course) | 
| Duration of response |  | Courses repeat every 28 days for up to 24 months in the absence of disease progression. | 
| Fetal hemoglobin levels as assessed thereafter |  | at baseline and every 28 days thereafter | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific