Nonsquamous Nonsmall Cell Neoplasm of Lung
Conditions
Keywords
Phase 2, histologically, confirmed, malignancy, metastatic, pemetrexed, carboplatin, carcinoma, non small cell lung, lung neoplasms, lung diseases
Brief summary
A randomized, double-blind, 3-arm (1:1:1) study in subjects with first-line Stage IV non-squamous NSCLC. The purpose is to test the efficacy and safety of demcizumab, when given in combination with carboplatin and pemetrexed compared to placebo. The administration of carboplatin and pemetrexed is a standard treatment for patients with non-squamous non-small cell lung cancer.
Detailed description
Patients will be enrolled at centers in North America, Western Europe, Australia and New Zealand. Up to 28 days (4 weeks) prior to treatment. If enrolled in the study, you will receive intravenous (in the vein) infusions of demcizumab (or placebo), carboplatin, and pemetrexed administered on the same day, every 21 days for 4 cycles, or until it has been shown that your cancer has gotten worse. If your physician decides to delay treatment with one of the agents due to side effects, the other agents may still be administered as scheduled. After 4 cycles, if you have stable or improved disease, you will continue to receive pemetrexed once every 21 days as maintenance therapy. After 8 cycles, if you have stable or improved disease, you may receive demcizumab (or placebo), every 21 days for 4 more cycles. You will undergo assessments every 6 weeks to determine the status of your disease.
Interventions
Sponsors
Celgene Corporation
OncoMed Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: 1. Signed Informed Consent Form 2. Histologically or cytologically confirmed Stage IV non-squamous NSCLC 3. Availability of FFPE (formalin-fixed paraffin-embedded) tumor tissue, either fresh core-needle-biopsied or archived 4. Age \> or = to 21 years 5. ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1 6. Disease that is measurable per RECIST v1.1 7. Adequate organ and marrow function 8. For women of childbearing potential, agreement to use two effective forms of contraception Main
Exclusion criteria
1. Histologically or cytologically documented, advanced, mixed non-small cell and small cell tumors or mixed adenosquamous carcinomas 2. NSCLC with known EGFR (epidermal growth factor receptor ) mutation or anaplastic lymphoma kinase (ALK) gene translocation (such as EML4 \[echinoderm microtubule-associated protein-like 4\]-ALK \[anaplastic lymphoma kinase\]) 3. Prior or ongoing therapy (including chemotherapy, antibody therapy, tyrosine kinase inhibitors, radiotherapy, immunotherapy, hormonal therapy, or investigational therapy) for the treatment of Stage IV non-squamous NSCLC 4. Evidence of tumor invading major blood vessels, cavitation of one or more pulmonary tumor mass(es) or tracheo-esophageal fistula 5. Brain metastases, leptomeningeal disease, uncontrolled seizure disorder, or active neurologic disease 6. Malignancies other than non-squamous NSCLC successfully treated within 3 years prior to randomization (with the exception of certain early-stage cancers) 7. History of a significant allergic reaction attributed to humanized or human monoclonal antibody therapy 8. Significant intercurrent illness defined as an illness that may result in the subject's death prior to their death from non-squamous NSCLC and/or significantly limit their ability to comply with the requirements of this study 9. Recent hemoptysis \>2.5 mL or serious bleeding from another site, known bleeding disorder or coagulopathy or therapeutic anti-coagulation 10. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization, or anticipation of need for major surgical procedure during the course of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. | Response assessment data was collected until the subject started alternative anti-cancer treatment or developed progressive disease, whichever occurred first, assessed up to approximately 26 months. | Investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 response rate (unconfirmed) in placebo/placebo arm to demcizumab/placebo arm and demcizumab/demcizumab arm combined in subjects with first-line stage IV non-small cell lung cancer (NSCLC). Response rate was based on Investigator-assessed best-overall-response (BOR) and was defined as the best unconfirmed response determined by RECIST version 1.1 recorded from the start of the treatment until disease progression in the following order of importance: CR, PR , SD, progressive disease (PD), not evaluable, or missing. |
Countries
Australia, Belgium, Italy, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Placebo Arm (Arm 1) Placebo plus pemetrexed and carboplatin (4 cycles), pemetrexed (4 cycles), placebo plus pemetrexed (4 cycles) | 25 |
| Demcizumab/Placebo Arm (Arm 2) Demcizumab plus pemetrexed and carboplatin (4 cycles), pemetrexed (4 cycles), placebo plus pemetrexed (4 cycles) | 28 |
| Demcizumab/Demcizumab Arm (Arm 3) Demcizumab plus pemetrexed and carboplatin (4 cycles), pemetrexed (4 cycles), demcizumab plus pemetrexed (4 cycles) | 29 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 |
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Disease progression | 14 | 15 | 17 |
| Overall Study | Lack of Subject Adherence to Protocol | 1 | 1 | 1 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo/Placebo Arm (Arm 1) | Total | Demcizumab/Demcizumab Arm (Arm 3) | Demcizumab/Placebo Arm (Arm 2) |
|---|---|---|---|---|
| Age, Continuous | 60 years | 62 years | 61 years | 66 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 77 Participants | 28 Participants | 26 Participants |
| Region of Enrollment Australia | 14 participants | 34 participants | 10 participants | 10 participants |
| Region of Enrollment Belgium | 0 participants | 2 participants | 1 participants | 1 participants |
| Region of Enrollment Italy | 2 participants | 7 participants | 3 participants | 2 participants |
| Region of Enrollment Spain | 4 participants | 19 participants | 8 participants | 7 participants |
| Region of Enrollment United States | 5 participants | 20 participants | 7 participants | 8 participants |
| Sex: Female, Male Female | 15 Participants | 42 Participants | 12 Participants | 15 Participants |
| Sex: Female, Male Male | 10 Participants | 40 Participants | 17 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 25 | 2 / 28 | 2 / 29 |
| other Total, other adverse events | 25 / 25 | 28 / 28 | 29 / 29 |
| serious Total, serious adverse events | 6 / 25 | 11 / 28 | 15 / 29 |
Outcome results
Primary
To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms.
Investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 response rate (unconfirmed) in placebo/placebo arm to demcizumab/placebo arm and demcizumab/demcizumab arm combined in subjects with first-line stage IV non-small cell lung cancer (NSCLC). Response rate was based on Investigator-assessed best-overall-response (BOR) and was defined as the best unconfirmed response determined by RECIST version 1.1 recorded from the start of the treatment until disease progression in the following order of importance: CR, PR , SD, progressive disease (PD), not evaluable, or missing.
Time frame: Response assessment data was collected until the subject started alternative anti-cancer treatment or developed progressive disease, whichever occurred first, assessed up to approximately 26 months.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo/Placebo Arm (Arm 1) | To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. | Progressive disease (PD) | 2 Participants |
| Placebo/Placebo Arm (Arm 1) | To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. | Partial response (PR) | 13 Participants |
| Placebo/Placebo Arm (Arm 1) | To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. | Complete response (CR) | 0 Participants |
| Placebo/Placebo Arm (Arm 1) | To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. | Stable disease (SD) | 10 Participants |
| Placebo/Placebo Arm (Arm 1) | To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. | Not evaluable (NE) | 0 Participants |
| Placebo/Placebo Arm (Arm 1) | To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. | Missing | 0 Participants |
| Demcizumab/Placebo Arm (Arm 2) | To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. | Not evaluable (NE) | 0 Participants |
| Demcizumab/Placebo Arm (Arm 2) | To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. | Missing | 0 Participants |
| Demcizumab/Placebo Arm (Arm 2) | To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. | Complete response (CR) | 0 Participants |
| Demcizumab/Placebo Arm (Arm 2) | To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. | Partial response (PR) | 10 Participants |
| Demcizumab/Placebo Arm (Arm 2) | To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. | Stable disease (SD) | 14 Participants |
| Demcizumab/Placebo Arm (Arm 2) | To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. | Progressive disease (PD) | 4 Participants |
| Demcizumab/Demcizumab Arm (Arm 3) | To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. | Stable disease (SD) | 15 Participants |
| Demcizumab/Demcizumab Arm (Arm 3) | To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. | Complete response (CR) | 0 Participants |
| Demcizumab/Demcizumab Arm (Arm 3) | To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. | Not evaluable (NE) | 0 Participants |
| Demcizumab/Demcizumab Arm (Arm 3) | To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. | Progressive disease (PD) | 5 Participants |
| Demcizumab/Demcizumab Arm (Arm 3) | To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. | Partial response (PR) | 6 Participants |
| Demcizumab/Demcizumab Arm (Arm 3) | To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. | Missing | 3 Participants |
Comparison: The Kaplan-Meier method was used to estimate both the survival curves and the median survival time. The 95% confidence interval (CI) for the median survival time was calculated. A p-value for treatment effect was generated using a stratified Cox proportional hazards model.p-value: =0.040195% CI: [0.013, 0.095]Log Rank