Study of Tarceva and Targretin Oral Capsules in Patients With Advanced Lung Cancer

• Sponsor: Konstantin Dragnev (Other)
• Overall Status: Completed
• CT.gov ID: NCT00125359
• Collaborator: Ligand Pharmaceuticals (Industry), Genentech, Inc. (Industry)
• Enrollment: 42
• Locations: 2
• Arm: 1
• Duration (Months): 103
• Patients Per Site: 21
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to learn about the effects of two new anticancer drugs, erlotinib (Tarceva) and bexarotene (Targretin), when treating patients with advanced lung cancer.

Erlotinib is approved by the Food and Drug Administration (FDA) for the treatment of non-small-cell lung cancer (NSCLC). Bexarotene is approved by the FDA for the treatment of cutaneous T-cell lymphoma. This combination of drugs is experimental.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-small-cell Lung	Drug: erlotinib and bexarotene	Phase 2

Detailed Description

This is a single institution open label phase II trial. Consecutive, eligible patients presenting with the diagnosis of advanced NSCLC are to be enrolled in this study. All eligible patients will receive continuous daily oral erlotinib 150 mg (Tarceva™) with daily bexarotene oral capsules 400 mg/m2 (Targretin®). The two agents will be taken at the same time. We anticipate the maximum accrual of 40 patients to this trial.

Patients will be evaluated by history, physical examination, and laboratory assessment every 4 weeks. Radiographic disease assessments by chest radiograph will be obtained every 4 weeks and computer tomography every 8 weeks or longer if clinically indicated. Whole body PET scan will be obtained at 10 days and 8 weeks. All radiographic studies will be sent to Medical Metrix Solutions (MMS) for an independent radiographic review of tumor response.

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Clinical Study of Erlotinib (Tarceva) and Bexarotene (Targretin) Oral Capsules in Patients With Advanced Non-small Cell Lung Cancer
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 All eligible patients will receive continuous daily oral erlotinib 150mg with daily bexarotene oral capsules 400mg.	Drug: erlotinib and bexarotene; Daily Erlotinib 150mg and daily bexarotene oral capsules 400mg.

Outcome Measures

Primary Outcome Measures

1. Radiographic Response Rates [Through study completion, an average of 1 year]

   Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Secondary Outcome Measures

1. Correlation of Early PET Responses With Objective Radiographic Responses. [Through study completion, an average of 1 year]

   PET response is assessed based on the guidelines of the European Organization for Research and Treatment of Cancer (EORTC) PET Study Group (Eur J Cancer 1999; 35(13):1773-82). PET response refers to the presence and measurement of the most current PET scan imaging when compared to baseline imaging. The amount of reduction in the disease from baseline to current imaging determines the extent to which the cancer has responded to treatment. Radiographic response is per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

2. Progression-free Survival and Overall Survival [Through study completion, an average of 1 year]

3. Evaluation of EGFR Mutations in Tumor Biopsies and Correlation of EGFR Mutations With Objective Radiographic Responses. [Through study completion, an average of 1 year]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Advanced NSCLC

• Prior chemotherapy or radiotherapy is allowed.

Exclusion Criteria:

• Hepatic or renal dysfunction

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Norris Cotton Cancer Center	Lebanon	New Hampshire	United States	03756
2	Mount Sinai School of Medicine	New York	New York	United States	10029

Sponsors and Collaborators

• Konstantin Dragnev
• Ligand Pharmaceuticals
• Genentech, Inc.

Investigators

• Principal Investigator: Konstantin H Dragnev, MD, Norris Cotton Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Konstantin Dragnev, Associate Professor of Medicine, Dartmouth-Hitchcock Medical Center
• ClinicalTrials.gov Identifier: NCT00125359
• Other Study ID Numbers: D-0440
• First Posted: Aug 1, 2005
• Last Update Posted: Jan 8, 2019
• Last Verified: Dec 1, 2018

• Keywords provided by Konstantin Dragnev, Associate Professor of Medicine, Dartmouth-Hitchcock Medical Center: tarceva; targretin; non-small cell lung cancer; Carcinoma, non-small cell lung cancer; NSCLC
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Erlotinib Hydrochloride; Bexarotene

Study Results

Participant Flow

Arm/Group Title	Single Arm Erlotinib + Bexarotene
Arm/Group Description	All eligible patients will receive continuous daily oral erlotinib 150mg with daily bexarotene oral capsules 400mg. erlotinib and bexarotene: Daily Erlotinib 150mg and daily bexarotene oral capsules 400mg.
Period Title: Overall Study
STARTED	42
COMPLETED	19
NOT COMPLETED	23

Baseline Characteristics

Arm/Group Title	Single Arm Erlotinib + Bexarotene
Arm/Group Description	All eligible patients will receive continuous daily oral erlotinib 150mg with daily bexarotene oral capsules 400mg. erlotinib and bexarotene: Daily Erlotinib 150mg and daily bexarotene oral capsules 400mg.
Overall Participants	42
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67
Sex: Female, Male (Count of Participants)
Female	22 52.4%
Male	20 47.6%
Region of Enrollment (participants) [Number]
United States	42 100%
Disease Stage IV (Count of Participants)
Count of Participants [Participants]	42 100%
Histopathology (participants) [Number]
Adenocarcinomas	28 66.7%
Bronchioloalveolar type	5 11.9%
Squamous cell carcinoma	2 4.8%
Non-small cell carcinomas not otherwise specified	10 23.8%
Prior anti-EGFR therapy (Count of Participants)
Received prior anti-EGFR therapy	9 21.4%
Did not receive prior anti-EGFR therapy	33 78.6%
Number of prior chemotherapies (chemotherapies) [Median (Full Range) ]
Median (Full Range) [chemotherapies]	2
Smoking status (Count of Participants)
Never smoker	7 16.7%
Current smoker	6 14.3%
Former smoker	29 69%

Outcome Measures

1. Primary Outcome

Title	Radiographic Response Rates
Description	Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time Frame	Through study completion, an average of 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm Erlotinib + Bexarotene
Arm/Group Description	All eligible patients will receive continuous daily oral erlotinib 150mg with daily bexarotene oral capsules 400mg. erlotinib and bexarotene: Daily Erlotinib 150mg and daily bexarotene oral capsules 400mg.
Measure Participants	19
Count of Participants [Participants]	19 45.2%

2. Secondary Outcome

Title	Correlation of Early PET Responses With Objective Radiographic Responses.
Description	PET response is assessed based on the guidelines of the European Organization for Research and Treatment of Cancer (EORTC) PET Study Group (Eur J Cancer 1999; 35(13):1773-82). PET response refers to the presence and measurement of the most current PET scan imaging when compared to baseline imaging. The amount of reduction in the disease from baseline to current imaging determines the extent to which the cancer has responded to treatment. Radiographic response is per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time Frame	Through study completion, an average of 1 year

Outcome Measure Data

Analysis Population Description

Number of participants analyzed is reported per achieved disease response noted in individual rows.

Arm/Group Title	Single Arm Erlotinib + Bexarotene
Arm/Group Description	All eligible patients will receive continuous daily oral erlotinib 150mg with daily bexarotene oral capsules 400mg. erlotinib and bexarotene: Daily Erlotinib 150mg and daily bexarotene oral capsules 400mg.
Measure Participants	14
Early PET metabolic response	1 2.4%
Early PET metabolic progression	0 0%
Early PET stable disease	0 0%
Early PET progression	0 0%
Early PET metabolic response	0 0%
Early PET metabolic progression	1 2.4%
Early PET stable disease	0 0%
Early PET progression	0 0%
Early PET metabolic response	0 0%
Early PET metabolic progression	0 0%
Early PET stable disease	1 2.4%
Early PET progression	1 2.4%
Early PET metabolic response	0 0%
Early PET metabolic progression	0 0%
Early PET stable disease	5 11.9%
Early PET progression	5 11.9%

3. Secondary Outcome

Title	Progression-free Survival and Overall Survival
Time Frame	Through study completion, an average of 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm Erlotinib + Bexarotene
Arm/Group Description	All eligible patients will receive continuous daily oral erlotinib 150mg with daily bexarotene oral capsules 400mg. erlotinib and bexarotene: Daily Erlotinib 150mg and daily bexarotene oral capsules 400mg.
Measure Participants	40
Time to progression	7
Overall survival	22

4. Secondary Outcome

Title	Evaluation of EGFR Mutations in Tumor Biopsies and Correlation of EGFR Mutations With Objective Radiographic Responses.
Time Frame	Through study completion, an average of 1 year

Outcome Measure Data

Analysis Population Description

Three patients had biopsies evaluated for EGFR mutations.

Arm/Group Title	Single Arm Erlotinib + Bexarotene
Arm/Group Description	All eligible patients will receive continuous daily oral erlotinib 150mg with daily bexarotene oral capsules 400mg. erlotinib and bexarotene: Daily Erlotinib 150mg and daily bexarotene oral capsules 400mg.
Measure Participants	3
Complete Response (CR) in EGFR Wild-Type	0 0%
Partial Response in EGFR Wild-Type	2 4.8%
CR in Activating EGFR mutation at exon 21	1 2.4%
PR in Activating EGFR mutation at exon 21	0 0%

Adverse Events

Arm/Group Title	Single Arm Erlotinib + Bexarotene
Arm/Group Description	All eligible patients will receive continuous daily oral erlotinib 150mg with daily bexarotene oral capsules 400mg. erlotinib and bexarotene: Daily Erlotinib 150mg and daily bexarotene oral capsules 400mg.
All Cause Mortality
	Single Arm Erlotinib + Bexarotene
	Affected / at Risk (%)	# Events
Total	4/42 (9.5%)
Serious Adverse Events
	Single Arm Erlotinib + Bexarotene
	Affected / at Risk (%)	# Events
Total	30/42 (71.4%)
Cardiac disorders
Chest pain	1/42 (2.4%)
Pericardial effusion	2/42 (4.8%)
Atrial fibrillation	1/42 (2.4%)
Infections and infestations
Bacterial pneumonia	1/42 (2.4%)
Musculoskeletal and connective tissue disorders
Back pain	1/42 (2.4%)
Pain	1/42 (2.4%)
Psychiatric disorders
Anxiety Disorder	1/42 (2.4%)
Mental status changes	1/42 (2.4%)
Renal and urinary disorders
Acute renal failure	1/42 (2.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	6/42 (14.3%)
Pleural effusion	3/42 (7.1%)
Hemoptysis	3/42 (7.1%)
Post-obstructive Pneumonia	2/42 (4.8%)
Pulmonary Embolism	2/42 (4.8%)
Pneumonia	2/42 (4.8%)
Pulmonary Hemorrhage	1/42 (2.4%)
Declining respiratory status	1/42 (2.4%)
Other (Not Including Serious) Adverse Events
	Single Arm Erlotinib + Bexarotene
	Affected / at Risk (%)	# Events
Total	14/42 (33.3%)
Blood and lymphatic system disorders
Increased white blood cell count	1/42 (2.4%)
Neutrophil count decreased	1/42 (2.4%)
Gastrointestinal disorders
Mouth sores	1/42 (2.4%)
General disorders
Fatigue	3/42 (7.1%)
Investigations
INR increased	1/42 (2.4%)
Activated partial thromboplastin time prolonged	1/42 (2.4%)
Investigations - Other, elevated granulocytes	1/42 (2.4%)
Cholesterol high	1/42 (2.4%)
Metabolism and nutrition disorders
Hypertriglyceridemia	5/42 (11.9%)	16
Hypernatremia	1/42 (2.4%)
Musculoskeletal and connective tissue disorders
Proximal muscle weakness	1/42 (2.4%)
Arm pain	1/42 (2.4%)
Psychiatric disorders
Hallucinations	1/42 (2.4%)

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.