A Study of Paclitaxel and Carboplatin in Combination With Bexarotene Oral Capsules in Patients With Advanced Lung Cancer

• Sponsor: Dartmouth-Hitchcock Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00153842
• Collaborator: Bristol-Myers Squibb (Industry), Ligand Pharmaceuticals (Industry)
• Enrollment: 33
• Location: 1
• Arm: 1
• Duration (Months): 91
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-small-cell Lung	Drug: Bexarotene (targretin); Drug: Bexarotene (targretin)	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I and II Clinical Studies of Paclitaxel and Carboplatin in Combination With Bexarotene Oral Capsules for the Treatment of Patients With Advanced Non-Small Cell Lung Cancer
• Study Start Date: Aug 1, 2001
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bexarotene Bexarotene oral capsules will be administered daily beginning on the initial day of chemotherapy (day 1).	Drug: Bexarotene (targretin); Bexarotene oral capsules will be administered daily beginning on the initial day of chemotherapy (day 1). Level 1: 300 mg; Other Names: Targretin, LGD1069 ; Drug: Bexarotene (targretin); Bexarotene oral capsules will be administered daily beginning on the intitial day of chemotherapy (Day 1). Level 2: 400 mg; Other Names: Targretin, LGD1069

Outcome Measures

Primary Outcome Measures

1. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Norris Cotton Cancer Center	Lebanon	New Hampshire	United States	03756

Sponsors and Collaborators

• Dartmouth-Hitchcock Medical Center
• Bristol-Myers Squibb
• Ligand Pharmaceuticals

Investigators

• Principal Investigator: James R Rigas, MD, Norris Cotton Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dartmouth-Hitchcock Medical Center
• ClinicalTrials.gov Identifier: NCT00153842
• Other Study ID Numbers: D-0109
• First Posted: Sep 12, 2005
• Last Update Posted: Mar 6, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by Dartmouth-Hitchcock Medical Center: NSCLC; Bexarotene; Targretin
• Additional relevant MeSH terms: Carcinoma, Non-Small-Cell Lung; Bexarotene

Study Results

Participant Flow

Arm/Group Title	Phase IB	Phase II
Arm/Group Description	Bexarotene 300mg vs 400mg administered with paclitaxel and carboplatin	Bexarotene 400mg in combination with Paraplatin and weekly Taxol.
Period Title: Overall Study
STARTED	26	7
COMPLETED	26	7
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Phase IB	Phase II	Total
Arm/Group Description	Bexarotene 300mg vs 400mg administered with paclitaxel and carboplatin	Bexarotene 400mg in combination with Paraplatin and weekly Taxol.	Total of all reporting groups
Overall Participants	26	7	33
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	19 73.1%	6 85.7%	25 75.8%
>=65 years	7 26.9%	1 14.3%	8 24.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.35 (9.79)	57 (13.99)	58.85 (10.61)
Sex: Female, Male (Count of Participants)
Female	11 42.3%	2 28.6%	13 39.4%
Male	15 57.7%	5 71.4%	20 60.6%
Region of Enrollment (participants) [Number]
United States	26 100%	7 100%	33 100%

Outcome Measures

1. Primary Outcome

Title	Bexarotene Oral Capsules Safety at Two Dose Levels (300 mg/m2 and 400 mg/m2) in Combination With Carboplatin and Taxol®.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase IB: Bexarotene 300mg, Paclitaxel and Carboplatin	Phase IB: Bexarotene 400mg, Paclitaxel and Carboplatin	Phase II
Arm/Group Description	Bexarotene 300mg administered with paclitaxel and carboplatin	Bexarotene 400mg administered with paclitaxel and carboplatin	Bexarotene 400mg administered with paclitaxel and carboplatin (Paraplatin and weekly Taxol)
Measure Participants	14	12	7
Number [participants experiencing IDLT]	1 3.8%	1 14.3%	0 0%

Adverse Events

Arm/Group Title	Phase IB - Bexarotene 300mg, Paclitaxel and Carboplatin		Phase IB - Bexarotene 400mg, Paclitaxel and Carboplatin		Phase II
Arm/Group Description	Bexarotene 300mg administered with paclitaxel and carboplatin		Bexarotene 400mg administered with paclitaxel and carboplatin		Bexarotene 400mg in combination with Paraplatin and weekly Taxol.
All Cause Mortality
	Phase IB - Bexarotene 300mg, Paclitaxel and Carboplatin		Phase IB - Bexarotene 400mg, Paclitaxel and Carboplatin		Phase II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/12 (0%)		0/7 (0%)
Serious Adverse Events
	Phase IB - Bexarotene 300mg, Paclitaxel and Carboplatin		Phase IB - Bexarotene 400mg, Paclitaxel and Carboplatin		Phase II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/14 (7.1%)		0/12 (0%)		2/7 (28.6%)
Blood and lymphatic system disorders
Myelosuppression	1/14 (7.1%)	1	0/12 (0%)	0	0/7 (0%)	0
Hypertriglyceridemia	0/14 (0%)	0	0/12 (0%)	0	2/7 (28.6%)	2
Other (Not Including Serious) Adverse Events
	Phase IB - Bexarotene 300mg, Paclitaxel and Carboplatin		Phase IB - Bexarotene 400mg, Paclitaxel and Carboplatin		Phase II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/12 (0%)		0/7 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.