Carcinoma, Non-Small-Cell Lung, Non-small Cell Lung Cancer, NSCLC
Conditions
Keywords
Erlotinib, Tarceva, Web based, Stage III NSCLC
Brief summary
This is a national, randomized, web-based, double-blind study to determine whether erlotinib (Tarceva) compared to placebo improves progression-free survival (PFS) for patients with inoperable, stage III NSCLC following concurrent docetaxel, carboplatin and thoracic radiotherapy. We hypothesize that the introduction of this orally active, well-tolerated agent following concurrent chemoradiation and prior to the emergence of drug resistance will prolong the progression-free survival by 40% (10 months → 14 months).
Detailed description
The promising activity of erlotinib as a single agent in advanced refractory NSCLC along with its oral administration and favorable adverse event profile makes this agent an excellent candidate to incorporate into combined modality therapy in the early stages of lung cancer. Based on these data, erlotinib is an attractive novel approach to maintenance therapy in unresectable stage III NSCLC following completion of concomitant chemoradiation. Although, a subset of patients with unresectable stage III NSCLC will be long-term survivors following chemotherapy and thoracic radiation therapy, the vast majority relapse within the first year following therapy and eventually die from chemotherapy refractory disease. We hypothesize that the introduction of an potent tyrosine kinase inhibitor to the epidermal growth factor receptor following effective concomitant chemoradiotherapy with docetaxel and carboplatin will prolong the progression-free survival time for these patients.
Interventions
Erlotinib 150mg orally each day. Patients will be treated on a continuous, once daily oral dosing schedule until disease progression, withdrawal of consent, unacceptable adverse events, death or completion of 3 years of therapy.
DRUGPlacebo
Matched placebo orally each day. Patients will be treated on a continuous, once daily oral dosing schedule until disease progression, withdrawal of consent, unacceptable adverse events death or completion of 3 years of therapy.
Sponsors
Sanofi
Genentech, Inc.
Dartmouth-Hitchcock Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Unresectable, stage IIIA or IIIB NSCLC (measurable disease is not required) * No evidence of metastatic disease * No prior treatment * Adequate organ function * Adequate pulmonary function (FEV \>= 1.0L or predicted FEV \>0.8L)
Exclusion criteria
* Metastasis * Prior treatment * Malignant pleural or pericardial effusion * Peripheral neuropathy \>= grade 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 5 years | Progression Free Survival is defined as time from randomization until documented disease progression or death from any cause. The Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.0) was used to determine disease progression. Irradiated target lesions were considered non-measurable disease. Symptomatic radiographic changes of irradiated non-measurable disease required pathologically confirmation or positive FDG-PET scan 6 months following completion of concurrent chemoradiation to be considered locoregional disease progression. Global deterioration of health status requiring discontinuation of treatment without objective evidence of progression was considered distant disease progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From date of randomization until the date of death from any cause, assessed up to 50 months | — |
| Percent of Participants Surviving 3 Years | 36 months | — |
| Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Concurrent Chemoradiation | 18 months | Number of participants with treatment-related serious adverse events (SAEs) observed in each SAE category for each arm relating to death, disability, life-threatening, hospitalization, and impairment/damage is reported. For participants with multiple SAEs, the SAE report having the strongest relationship to study drug is summarized. |
| Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Erlotinib and Placebo | 18 months | Number of participants with treatment-related serious adverse events (SAEs) observed in each SAE category for each arm relating to death, disability, life-threatening, hospitalization, and impairment/damage is reported. For participants with multiple SAEs, the SAE report having the strongest relationship to study drug is summarized. |
Countries
United States
Participant flow
Recruitment details
Period 1: 245 patients were registered & randomized. Of those, 10 patients were ineligible due to incorrect stage, withdrawal of consent, inability to meet radiation therapy parameters, and inadequate functional status. The number of participants for each specific reason for ineligibility is unknown. They did not receive any study intervention.
Pre-assignment details
Period 2:Study drug dispensed to only chemoradiation patients who did not experience disease progression, consent withdrawal, death, investigators discretion, or toxicity.
Participants by arm
| Arm | Count |
|---|---|
| Tarceva Tarceva 150mg
Erlotinib (tarceva): Erlotinib 150mg orally each day. Patients will be treated on a continuous, once daily oral dosing schedule until disease progression, withdrawal of consent, unacceptable adverse events, death or completion of 3 years of therapy. | 123 |
| Placebo Matched Placebo
Placebo: Matched placebo orally each day. Patients will be treated on a continuous, once daily oral dosing schedule until disease progression, withdrawal of consent, unacceptable adverse events death or completion of 3 years of therapy. | 122 |
| Total | 245 |
Baseline characteristics
| Characteristic | Placebo | Total | Tarceva |
|---|---|---|---|
| Age, Continuous | 67 years | 67.5 years | 68 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 13 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 14 Participants | 7 Participants |
| Race (NIH/OMB) White | 106 Participants | 215 Participants | 109 Participants |
| Sex: Female, Male Female | 55 Participants | 100 Participants | 45 Participants |
| Sex: Female, Male Male | 67 Participants | 145 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 26 / 118 | 27 / 117 | 43 / 77 | 40 / 75 |
| other Total, other adverse events | 12 / 118 | 8 / 117 | 8 / 77 | 0 / 75 |
| serious Total, serious adverse events | 36 / 118 | 38 / 117 | 39 / 77 | 23 / 75 |
Outcome results
Primary
Progression Free Survival
Progression Free Survival is defined as time from randomization until documented disease progression or death from any cause. The Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.0) was used to determine disease progression. Irradiated target lesions were considered non-measurable disease. Symptomatic radiographic changes of irradiated non-measurable disease required pathologically confirmation or positive FDG-PET scan 6 months following completion of concurrent chemoradiation to be considered locoregional disease progression. Global deterioration of health status requiring discontinuation of treatment without objective evidence of progression was considered distant disease progression.
Time frame: 5 years
Population: NA = not available; The data cannot be located/provided due to the PI leaving the institution.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tarceva | Progression Free Survival | 7.4 Months |
| Placebo | Progression Free Survival | 8.1 Months |
p-value: 0.16595% CI: [0.65, 1.33]Log Rank
Secondary
Overall Survival
Time frame: From date of randomization until the date of death from any cause, assessed up to 50 months
Population: NA = not available; The data cannot be located/provided due to the PI leaving the institution.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tarceva | Overall Survival | 16.5 Months |
| Placebo | Overall Survival | 20.3 Months |
p-value: 0.3295% CI: [0.85, 1.63]Log Rank
Secondary
Percent of Participants Surviving 3 Years
Time frame: 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tarceva | Percent of Participants Surviving 3 Years | 37 percentage of participants |
| Placebo | Percent of Participants Surviving 3 Years | 41 percentage of participants |
Secondary
Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Concurrent Chemoradiation
Number of participants with treatment-related serious adverse events (SAEs) observed in each SAE category for each arm relating to death, disability, life-threatening, hospitalization, and impairment/damage is reported. For participants with multiple SAEs, the SAE report having the strongest relationship to study drug is summarized.
Time frame: 18 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tarceva | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Concurrent Chemoradiation | Death | 7 Participants |
| Tarceva | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Concurrent Chemoradiation | Disability | 0 Participants |
| Tarceva | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Concurrent Chemoradiation | Life-threatening | 2 Participants |
| Tarceva | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Concurrent Chemoradiation | Hospitalization | 26 Participants |
| Tarceva | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Concurrent Chemoradiation | Impairment/damange | 3 Participants |
| Tarceva | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Concurrent Chemoradiation | Other | 1 Participants |
| Placebo | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Concurrent Chemoradiation | Impairment/damange | 3 Participants |
| Placebo | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Concurrent Chemoradiation | Death | 6 Participants |
| Placebo | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Concurrent Chemoradiation | Hospitalization | 36 Participants |
| Placebo | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Concurrent Chemoradiation | Disability | 0 Participants |
| Placebo | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Concurrent Chemoradiation | Other | 0 Participants |
| Placebo | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Concurrent Chemoradiation | Life-threatening | 4 Participants |
Secondary
Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Erlotinib and Placebo
Number of participants with treatment-related serious adverse events (SAEs) observed in each SAE category for each arm relating to death, disability, life-threatening, hospitalization, and impairment/damage is reported. For participants with multiple SAEs, the SAE report having the strongest relationship to study drug is summarized.
Time frame: 18 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tarceva | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Erlotinib and Placebo | Disability | 0 Participants |
| Tarceva | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Erlotinib and Placebo | Hospitalization (initial or prolonged) | 30 Participants |
| Tarceva | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Erlotinib and Placebo | Death | 10 Participants |
| Tarceva | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Erlotinib and Placebo | Life-threatening | 1 Participants |
| Tarceva | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Erlotinib and Placebo | Other | 1 Participants |
| Tarceva | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Erlotinib and Placebo | Impairment/damange | 2 Participants |
| Placebo | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Erlotinib and Placebo | Other | 0 Participants |
| Placebo | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Erlotinib and Placebo | Death | 6 Participants |
| Placebo | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Erlotinib and Placebo | Disability | 0 Participants |
| Placebo | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Erlotinib and Placebo | Life-threatening | 1 Participants |
| Placebo | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Erlotinib and Placebo | Hospitalization (initial or prolonged) | 23 Participants |
| Placebo | Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Erlotinib and Placebo | Impairment/damange | 1 Participants |