Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
erlotinib, NSCLC, chemotherapy, platinum, lung, lung cancer
Brief summary
This study was conducted to compare the activities of erlotinib to that of intravenous, platinum-based therapy in the treatment of non-small cell lung cancer (NSCLC). The goal of this trial was to demonstrate clinical equivalence of erlotinib to platinum-based frontline therapy, compared to historical controls.
Detailed description
To compare the activities (the progression-free survival, the incidence and severity of toxicities, and reversibility of toxicities) of erlotinib to that of platinum-based therapy in NSCLC. A sequential therapy design has been chosen such that all patients will receive any potential benefits of both platinum-based and erlotinib therapy, without compromising survival by denying anyone potential therapy. With this design, progression-free survival will be tracked by treatment received. However, data will be generated which will show the safety and efficacy of erlotinib in the frontline setting (alone and with historical comparison to platinum-based therapy), as well as the potential safety and activity of platinum-based therapy in the second-line (post-erlotinib) setting. This should allow for the demonstration of the relative median time to progression, objective response and clinical benefit rates, overall survival, and safety and tolerability of erlotinib and platinum-based therapy in both the frontline and second-line settings in NSCLC. Also, in this fashion, the treatments serve as controls for each other, as well as being compared to historical controls; in the first line treatment portion, the platinum-based regimens serve as the historical control, while in the second-line setting, erlotinib serves as the historical control arm.
Interventions
DRUGErlotinib
Erlotinib will be administered for at least 2 cycles (6 weeks) and for a maximum of 8 months. Upon progression or intolerance to erlotinib, standard of care platinum-based chemotherapy (per the choice of the treating physician) is administered every 3 weeks. Physicians can adjust dose, schedule, or supportive care to the benefit of the patient
Intravenous chemotherapy combination per physician discretion every 3 weeks for at least 2 cycles
Sponsors
Genentech, Inc.
New Mexico Cancer Research Alliance
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Prior chemotherapy will be allowed for other invasive malignancies, provided at least five years has elapsed since the completion of therapy and enrollment on this protocol. No prior chemotherapy for metastatic non-small cell lung cancer (NSCLC) will be allowed. Prior adjuvant or neoadjuvant chemotherapy for NSCLC will be allowed, provided at least six months have elapsed from the last dose of chemotherapy to the documentation of relapsed disease. Baseline laboratory values (bone marrow, renal, hepatic): * Adequate bone marrow function: * Absolute neutrophil count \>1000/µL * Platelet count \>100'000/µL * Renal function: * Serum creatinine \< 2.0 mg % * Hepatic function: * Bilirubin \<1.5x normal * Serum calcium \< 12 mg/dl Other Eligibility Criteria: * Signed Informed Consent * Eastern Cooperative Oncology Group (ECOG)/Zubrod/Southwest Oncology Group (SWOG) Performance Status \<2 (Karnofsky Performance Status \> 70%) * Life expectancy \> 8 weeks * Male or female' age \>18 years * Patients of childbearing potential must be using an effective means of contraception. * Histologic diagnosis of NSCLC that is advanced and cannot be treated adequately by radiotherapy or surgery; or metastatic disease
Exclusion criteria
* Prior therapy with an epidermal growth factor receptor inhibitor, including erlotinib, gefitinib, and cetuximab, as well as any investigational HER-1 inhibiting agent * Pregnant or lactating females * Myocardial infarction or ischemia within the 6 months before Cycle 0' Day 0 * Uncontrolled' clinically significant dysrhythmia * History of prior malignancy within the prior five years, with the exception of non-melanoma carcinomas of the skin, and carcinoma in situ of the cervix * Prior radiotherapy to an indicator lesion unless there is objective evidence of tumor growth in that lesion * Uncontrolled metastatic disease of the central nervous system (previously treated, stable disease is allowable on this protocol) * Radiotherapy within the 2 weeks before Cycle 1' Day 1 * Surgery within the 2 weeks before Cycle 1' Day 1 * Any co morbid condition that' in the view of the attending physician' renders the patient at high risk from treatment complications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | 5 years | — |
| Toxicity Profile | 28 days after last on-study treatment | Toxicities are assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 3.0. Toxicities are reported as the number of patients who experienced grade 3 or grade 4 adverse events after receiving at least one dose of on-study treatment. |
Countries
United States
Participant flow
Recruitment details
Recruitment began 07/13/2006 and ended 02/09/2009. All patients were recruited through medical clinics in New Mexico, USA.
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib Followed by Chemotherapy Erlotinib at 150 mg orally per day for at least 2 cycles (6 weeks) and for a maximum of 8 months. Upon progression or drug intolerance, this is followed by standard of care platinum-based chemotherapy selected by the treating physician, every 3 weeks for at least 2 cycles | 43 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Death | 4 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Progressive disease | 13 |
Baseline characteristics
| Characteristic | Erlotinib Followed by Chemotherapy |
|---|---|
| Age, Continuous | 68 years |
| Region of Enrollment United States | 43 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 25 / 43 |
| serious Total, serious adverse events | 5 / 43 |
Outcome results
Primary
Progression-free Survival (PFS)
Time frame: 5 years
Population: This study was terminated early; no results are available. The number of patients who completed treatment and therefore the number of evaluable patients was too low to accurately calculate endpoints.
Primary
Toxicity Profile
Toxicities are assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 3.0. Toxicities are reported as the number of patients who experienced grade 3 or grade 4 adverse events after receiving at least one dose of on-study treatment.
Time frame: 28 days after last on-study treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib Followed by Chemotherapy | Toxicity Profile | Acne | 1 participants |
| Erlotinib Followed by Chemotherapy | Toxicity Profile | Anorexia | 1 participants |
| Erlotinib Followed by Chemotherapy | Toxicity Profile | Confusion | 1 participants |
| Erlotinib Followed by Chemotherapy | Toxicity Profile | Dehydration | 1 participants |
| Erlotinib Followed by Chemotherapy | Toxicity Profile | Diarrhea | 2 participants |
| Erlotinib Followed by Chemotherapy | Toxicity Profile | Dyspnea | 3 participants |
| Erlotinib Followed by Chemotherapy | Toxicity Profile | Fatigue | 8 participants |
| Erlotinib Followed by Chemotherapy | Toxicity Profile | Nasal hemorrhage | 1 participants |
| Erlotinib Followed by Chemotherapy | Toxicity Profile | Insomnia | 1 participants |
| Erlotinib Followed by Chemotherapy | Toxicity Profile | Kidney pain | 1 participants |
| Erlotinib Followed by Chemotherapy | Toxicity Profile | Lymphocyte count decreased | 1 participants |
| Erlotinib Followed by Chemotherapy | Toxicity Profile | Muscle weakness | 1 participants |
| Erlotinib Followed by Chemotherapy | Toxicity Profile | Neutrophil count decreased | 2 participants |
| Erlotinib Followed by Chemotherapy | Toxicity Profile | Desquamating rash | 1 participants |
| Erlotinib Followed by Chemotherapy | Toxicity Profile | Syncope | 1 participants |
| Erlotinib Followed by Chemotherapy | Toxicity Profile | Thrombosis (clotting) | 1 participants |