Carcinoma, Non-small-cell Lung
Conditions
Keywords
tarceva, targretin, non-small cell lung cancer, Carcinoma, non-small cell lung cancer, NSCLC
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.
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.
Interventions
DRUGerlotinib and bexarotene
Daily Erlotinib 150mg and daily bexarotene oral capsules 400mg.
Sponsors
Ligand Pharmaceuticals
Genentech, Inc.
Konstantin Dragnev
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
* Advanced NSCLC * Prior chemotherapy or radiotherapy is allowed.
Exclusion criteria
* Hepatic or renal dysfunction
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Progression-free Survival and Overall Survival | Through study completion, an average of 1 year | — |
| Evaluation of EGFR Mutations in Tumor Biopsies and Correlation of EGFR Mutations With Objective Radiographic Responses. | Through study completion, an average of 1 year | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Arm Erlotinib + Bexarotene 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. | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Death | 4 |
| Overall Study | Physician Decision | 14 |
Baseline characteristics
| Characteristic | Single Arm Erlotinib + Bexarotene |
|---|---|
| Age, Continuous | 67 years |
| Disease Stage IV | 42 Participants |
| Histopathology Adenocarcinomas | 28 participants |
| Histopathology Bronchioloalveolar type | 5 participants |
| Histopathology Non-small cell carcinomas not otherwise specified | 10 participants |
| Histopathology Squamous cell carcinoma | 2 participants |
| Number of prior chemotherapies | 2 chemotherapies |
| Prior anti-EGFR therapy Did not receive prior anti-EGFR therapy | 33 Participants |
| Prior anti-EGFR therapy Received prior anti-EGFR therapy | 9 Participants |
| Region of Enrollment United States | 42 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 20 Participants |
| Smoking status Current smoker | 6 Participants |
| Smoking status Former smoker | 29 Participants |
| Smoking status Never smoker | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 42 |
| other Total, other adverse events | 14 / 42 |
| serious Total, serious adverse events | 30 / 42 |
Outcome results
Primary
Radiographic Response Rates
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Arm Erlotinib + Bexarotene | Radiographic Response Rates | 19 Participants |
Secondary
Correlation of Early PET Responses With Objective Radiographic Responses.
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
Population: Number of participants analyzed is reported per achieved disease response noted in individual rows.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Single Arm Erlotinib + Bexarotene | Correlation of Early PET Responses With Objective Radiographic Responses. | Computed tomography complete response | Early PET metabolic response | 1 Participants |
| Single Arm Erlotinib + Bexarotene | Correlation of Early PET Responses With Objective Radiographic Responses. | Computed tomography complete response | Early PET metabolic progression | 0 Participants |
| Single Arm Erlotinib + Bexarotene | Correlation of Early PET Responses With Objective Radiographic Responses. | Computed tomography partial response | Early PET metabolic progression | 1 Participants |
| Single Arm Erlotinib + Bexarotene | Correlation of Early PET Responses With Objective Radiographic Responses. | Computed tomography partial response | Early PET metabolic response | 0 Participants |
| Single Arm Erlotinib + Bexarotene | Correlation of Early PET Responses With Objective Radiographic Responses. | Computed tomography stable disease | Early PET progression | 1 Participants |
| Single Arm Erlotinib + Bexarotene | Correlation of Early PET Responses With Objective Radiographic Responses. | Computed tomography disease progression | Early PET metabolic response | 0 Participants |
| Single Arm Erlotinib + Bexarotene | Correlation of Early PET Responses With Objective Radiographic Responses. | Computed tomography disease progression | Early PET metabolic progression | 0 Participants |
| Single Arm Erlotinib + Bexarotene | Correlation of Early PET Responses With Objective Radiographic Responses. | Computed tomography disease progression | Early PET stable disease | 5 Participants |
| Single Arm Erlotinib + Bexarotene | Correlation of Early PET Responses With Objective Radiographic Responses. | Computed tomography disease progression | Early PET progression | 5 Participants |
| Single Arm Erlotinib + Bexarotene | Correlation of Early PET Responses With Objective Radiographic Responses. | Computed tomography complete response | Early PET stable disease | 0 Participants |
| Single Arm Erlotinib + Bexarotene | Correlation of Early PET Responses With Objective Radiographic Responses. | Computed tomography complete response | Early PET progression | 0 Participants |
| Single Arm Erlotinib + Bexarotene | Correlation of Early PET Responses With Objective Radiographic Responses. | Computed tomography partial response | Early PET stable disease | 0 Participants |
| Single Arm Erlotinib + Bexarotene | Correlation of Early PET Responses With Objective Radiographic Responses. | Computed tomography partial response | Early PET progression | 0 Participants |
| Single Arm Erlotinib + Bexarotene | Correlation of Early PET Responses With Objective Radiographic Responses. | Computed tomography stable disease | Early PET metabolic response | 0 Participants |
| Single Arm Erlotinib + Bexarotene | Correlation of Early PET Responses With Objective Radiographic Responses. | Computed tomography stable disease | Early PET metabolic progression | 0 Participants |
| Single Arm Erlotinib + Bexarotene | Correlation of Early PET Responses With Objective Radiographic Responses. | Computed tomography stable disease | Early PET stable disease | 1 Participants |
Secondary
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
Population: Three patients had biopsies evaluated for EGFR mutations.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Single Arm Erlotinib + Bexarotene | Evaluation of EGFR Mutations in Tumor Biopsies and Correlation of EGFR Mutations With Objective Radiographic Responses. | Complete Response (CR) in EGFR Wild-Type | 0 Participants |
| Single Arm Erlotinib + Bexarotene | Evaluation of EGFR Mutations in Tumor Biopsies and Correlation of EGFR Mutations With Objective Radiographic Responses. | Partial Response in EGFR Wild-Type | 2 Participants |
| Single Arm Erlotinib + Bexarotene | Evaluation of EGFR Mutations in Tumor Biopsies and Correlation of EGFR Mutations With Objective Radiographic Responses. | CR in Activating EGFR mutation at exon 21 | 1 Participants |
| Single Arm Erlotinib + Bexarotene | Evaluation of EGFR Mutations in Tumor Biopsies and Correlation of EGFR Mutations With Objective Radiographic Responses. | PR in Activating EGFR mutation at exon 21 | 0 Participants |
Secondary
Progression-free Survival and Overall Survival
Time frame: Through study completion, an average of 1 year
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Single Arm Erlotinib + Bexarotene | Progression-free Survival and Overall Survival | Time to progression | 7 Weeks |
| Single Arm Erlotinib + Bexarotene | Progression-free Survival and Overall Survival | Overall survival | 22 Weeks |