Carcinoma, Non-small-cell Lung
Conditions
Keywords
NSCLC, Bexarotene, Targretin
Brief summary
The primary aim is to evaluate the safety (Phase I components) of administering bexarotene (Targretin®, LGD1069) oral capsules in combination with two Taxol® and carboplatin (Paraplatin®) schedules to patients with stage IIIB and IV non-small cell lung cancer. This study will also evaluate the preliminary efficacy (Phase II component) of bexarotene oral capsules in combination with the weekly Taxol® schedule and carboplatin in these patients.
Detailed description
The phase I portion of the study will evaluate the safety of administering bexarotene oral capsules daily at two dose levels (300 mg/m2 and 400 mg/m2) in combination with carboplatin and Taxol®. At least 6 patients will be entered onto each dose level. Doses will not be escalated over the course of treatment of an individual patient. The recommended Phase II dose is defined as the highest dose of bexarotene oral capsules (300 mg/m2 or 400 mg/m2) in combination with carboplatin and Taxol® that induces DLT in fewer than or equal to 33% of patients. The sequential phase II portion of the study will evaluate the efficacy of bexarotene oral capsules in combination with carboplatin and weekly Taxol® in patients with advanced non-small cell lung cancer. The efficacy will be gauged according to the rate of major response where, by definition, a major response occurs if a patient achieves either complete remission (CR) or partial remission (PR). For these patients a true response rate of 20% or greater is sufficiently large to warrant further investigation. A true response rate of 10% or less indicates that the combination is less active.
Interventions
Bexarotene oral capsules will be administered daily beginning on the initial day of chemotherapy (day 1). Level 1: 300 mg
Sponsors
Bristol-Myers Squibb
Ligand Pharmaceuticals
Dartmouth-Hitchcock Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* unresectable stage IIIB or IV NSCLC * adequate bone marrow, hepatic, thyroid and renal function
Exclusion criteria
* peripheral neuropathy \>= grade 2 * gastrointestinal abnormalities * known hypersensitivity to retinoids
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bexarotene Oral Capsules Safety at Two Dose Levels (300 mg/m2 and 400 mg/m2) in Combination With Carboplatin and Taxol®. | 36 months | At least 6 patients will be entered onto each dose level. Doses will not be escalated over the course of treatment of an individual patient. For the purpose of this protocol, an initial-dose-limiting toxicity (IDLT) is defined as a clinical observation that is, in the judgment of the Investigator, both attributable to the administration of bexarotene and necessitates a reduction in dose, suspension or discontinuation of study drug because of a NCI CTC Grade 3 or 4 level toxicity (with the exception of elevated lipids). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase IB Bexarotene 300mg vs 400mg administered with paclitaxel and carboplatin | 26 |
| Phase II Bexarotene 400mg in combination with Paraplatin and weekly Taxol. | 7 |
| Total | 33 |
Baseline characteristics
| Characteristic | Phase II | Phase IB | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 7 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 19 Participants | 25 Participants |
| Age, Continuous | 57 years STANDARD_DEVIATION 13.99 | 59.35 years STANDARD_DEVIATION 9.79 | 58.85 years STANDARD_DEVIATION 10.61 |
| Region of Enrollment United States | 7 participants | 26 participants | 33 participants |
| Sex: Female, Male Female | 2 Participants | 11 Participants | 13 Participants |
| Sex: Female, Male Male | 5 Participants | 15 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 12 | 0 / 7 |
| other Total, other adverse events | 0 / 14 | 0 / 12 | 0 / 7 |
| serious Total, serious adverse events | 1 / 14 | 0 / 12 | 2 / 7 |
Outcome results
Primary
Bexarotene Oral Capsules Safety at Two Dose Levels (300 mg/m2 and 400 mg/m2) in Combination With Carboplatin and Taxol®.
At least 6 patients will be entered onto each dose level. Doses will not be escalated over the course of treatment of an individual patient. For the purpose of this protocol, an initial-dose-limiting toxicity (IDLT) is defined as a clinical observation that is, in the judgment of the Investigator, both attributable to the administration of bexarotene and necessitates a reduction in dose, suspension or discontinuation of study drug because of a NCI CTC Grade 3 or 4 level toxicity (with the exception of elevated lipids).
Time frame: 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase IB: Bexarotene 300mg, Paclitaxel and Carboplatin | Bexarotene Oral Capsules Safety at Two Dose Levels (300 mg/m2 and 400 mg/m2) in Combination With Carboplatin and Taxol®. | 1 participants experiencing IDLT |
| Phase IB: Bexarotene 400mg, Paclitaxel and Carboplatin | Bexarotene Oral Capsules Safety at Two Dose Levels (300 mg/m2 and 400 mg/m2) in Combination With Carboplatin and Taxol®. | 1 participants experiencing IDLT |
| Phase II | Bexarotene Oral Capsules Safety at Two Dose Levels (300 mg/m2 and 400 mg/m2) in Combination With Carboplatin and Taxol®. | 0 participants experiencing IDLT |