Small Cell Lung Cancer
Conditions
Keywords
SCLC, SALUTE, Lung Cancer, Avastin
Brief summary
This is a placebo-controlled, double-blind, multicenter, randomized study for preliminary evaluation of the efficacy and safety of combining bevacizumab with cisplatin (or carboplatin) and etoposide in patients with previously untreated extensive-stage small cell lung cancer (SCLC).
Interventions
DRUGBevacizumab
Bevacizumab 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death.
DRUGChemotherapy
Chemotherapy = cisplatin (or carboplatin) + etoposide. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve \[AUC\]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles.
DRUGPlacebo
Placebo 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically documented small cell carcinoma of the bronchus, classified as extensive-stage disease * Measurable disease or lesions * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Exclusion criteria
* Life expectancy of \< 12 weeks * Current, recent, or planned participation in another experimental drug study * Ongoing or active infection * Active malignancy other than SCLC or superficial basal/squamous cell carcinoma within the previous 5 years * Prior systemic therapy, radiation therapy, or surgery for SCLC * Inadequate bone marrow function, renal function, or hepatic function * Serum sodium of \< 120 mg/dL * Inadequately controlled hypertension * History of hypertensive crisis or hypertensive encephalopathy * New York Heart Association Class II or greater congestive heart failure * History of myocardial infarction or unstable angina within 6 months prior to study enrollment * History of stroke or transient ischemic attack within 6 months prior to study enrollment * Known central nervous system disease, except for brain metastases treated with whole-brain radiotherapy * Significant vascular disease or recent peripheral arterial thrombosis within 6 months prior to study enrollment * History of hemoptysis within 4 weeks prior to study enrollment * Evidence of bleeding diathesis or coagulopathy in the absence of therapeutic anticoagulation * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of a need for a major surgical procedure during the course of the study * Core biopsy or other minor surgical procedure, including placement of a vascular access device, within 7 days prior to Day 1 * History of abdominal fistula or gastrointestinal perforation within 6 months prior to study enrollment * Serious, non-healing wound, active ulcer, or untreated bone fracture * Known hypersensitivity to any component of bevacizumab * Pregnant (positive pregnancy test) or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Randomization until progression or lost to follow-up (up to 2 years) | Duration of PFS, defined as the time from randomization to disease progression or on-study death, whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Randomization until death or lost of follow-up (up to 27 months) | Duration of overall survival from randomization until death or loss to follow-up |
| Percentage of Participants With an Objective Response | Randomization until progression or lost to follow-up (up to 2 years) | Objective response was defined as a complete or partial response (per RECIST) determined by two investigator assessments conducted at least 4 weeks apart. Complete Response (CR), Partial Response (PR), Incomplete Response (IR), Stable Disease (SD) (per RECIST): Target Lesions Non-Target Lesions New Lesions Overall Response CR CR No CR CR IR/SD No PR PR Non-PD No PR |
| Number of Participants With an Objective Response | Randomization until progression or lost to follow-up (up to 2 years) | Objective response was defined as a complete or partial response (per RECIST) determined by two investigator assessments conducted at least 4 weeks apart. Complete Response (CR), Partial Response (PR), Incomplete Response (IR), Stable Disease (SD) (per RECIST): Target Lesions Non-Target Lesions New Lesions Overall Response CR CR No CR CR IR/SD No PR PR Non-PD No PR |
| Duration of Objective Response | Randomization until progression or lost to follow-up (up to 2 years) | Duration of response was defined as time from the first response date to disease progression or on-study death (i.e., death occurring any time from randomization to 30 days after the final treatment with bevacizumab/placebo). Objective response was defined as a complete or partial response (per RECIST) determined by two investigator assessments conducted at least 4 weeks apart. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo+Chemotherapy Chemotherapy = cisplatin (or carboplatin) + etoposide. Placebo 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve \[AUC\]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles. | 50 |
| Bevacizumab+Chemotherapy Chemotherapy = cisplatin (or carboplatin) + etoposide. Bevacizumab 15 mg/kg by intravenous (IV) infusion on Day 1 of each of the first four 21-day cycles during chemotherapy, followed by single agent administration until disease progression, unacceptable toxicity, discontinuation from study, or death. Cisplatin 75 mg/m² IV on Day 1 of each of the first four 21-day cycles OR carboplatin (area under the curve \[AUC\]=5 mg/mL/min, per Calvert formula) IV on Day 1 of each of the first four 21-day cycles; etoposide 100 mg/m² on Days 1-3 of each of the first four 21-day cycles. | 52 |
| Total | 102 |
Baseline characteristics
| Characteristic | Bevacizumab+Chemotherapy | Total | Placebo+Chemotherapy |
|---|---|---|---|
| Age Continuous | 61.3 years STANDARD_DEVIATION 8.5 | 62.7 years STANDARD_DEVIATION 9.3 | 64.0 years STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 26 Participants | 46 Participants | 20 Participants |
| Sex: Female, Male Male | 26 Participants | 56 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 31 / 47 | 35 / 51 |
| serious Total, serious adverse events | 11 / 47 | 20 / 51 |
Outcome results
Primary
Progression-free Survival (PFS)
Duration of PFS, defined as the time from randomization to disease progression or on-study death, whichever occurred first.
Time frame: Randomization until progression or lost to follow-up (up to 2 years)
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo+Chemotherapy | Progression-free Survival (PFS) | 4.4 Months |
| Bevacizumab+Chemotherapy | Progression-free Survival (PFS) | 5.5 Months |
p-value: 0.009795% CI: [0.323, 0.862]Log Rank
Secondary
Duration of Objective Response
Duration of response was defined as time from the first response date to disease progression or on-study death (i.e., death occurring any time from randomization to 30 days after the final treatment with bevacizumab/placebo). Objective response was defined as a complete or partial response (per RECIST) determined by two investigator assessments conducted at least 4 weeks apart.
Time frame: Randomization until progression or lost to follow-up (up to 2 years)
Population: Randomized patients with measurable disease at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo+Chemotherapy | Duration of Objective Response | 3.2 Months |
| Bevacizumab+Chemotherapy | Duration of Objective Response | 4.7 Months |
p-value: 0.001195% CI: [0.144, 0.644]Log Rank
Secondary
Number of Participants With an Objective Response
Objective response was defined as a complete or partial response (per RECIST) determined by two investigator assessments conducted at least 4 weeks apart. Complete Response (CR), Partial Response (PR), Incomplete Response (IR), Stable Disease (SD) (per RECIST): Target Lesions Non-Target Lesions New Lesions Overall Response CR CR No CR CR IR/SD No PR PR Non-PD No PR
Time frame: Randomization until progression or lost to follow-up (up to 2 years)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo+Chemotherapy | Number of Participants With an Objective Response | 24 number of participants |
| Bevacizumab+Chemotherapy | Number of Participants With an Objective Response | 30 number of participants |
Secondary
Overall Survival
Duration of overall survival from randomization until death or loss to follow-up
Time frame: Randomization until death or lost of follow-up (up to 27 months)
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo+Chemotherapy | Overall Survival | 10.9 Months |
| Bevacizumab+Chemotherapy | Overall Survival | 9.4 Months |
p-value: 0.605495% CI: [0.66, 2.039]Log Rank
Secondary
Percentage of Participants With an Objective Response
Objective response was defined as a complete or partial response (per RECIST) determined by two investigator assessments conducted at least 4 weeks apart. Complete Response (CR), Partial Response (PR), Incomplete Response (IR), Stable Disease (SD) (per RECIST): Target Lesions Non-Target Lesions New Lesions Overall Response CR CR No CR CR IR/SD No PR PR Non-PD No PR
Time frame: Randomization until progression or lost to follow-up (up to 2 years)
Population: Intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo+Chemotherapy | Percentage of Participants With an Objective Response | 48.0 Percentage of participants |
| Bevacizumab+Chemotherapy | Percentage of Participants With an Objective Response | 57.7 Percentage of participants |
p-value: 0.326995% CI: [-9.6, 29]Chi-squared