An Open-label, Randomized, Phase IIIb Trial Evaluating the Efficacy and Safety of Standard of Care +/- Continuous Bevacizumab Treatment Beyond Progression of Disease (PD) in Patients With Advanced Non-squamous Non-small Cell Lung Cancer (NSCLC) After First Line Treatment With Bevacizumab Plus a Platinum Doublet-containing Chemotherapy
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 485
- Locations
- 179
- Primary Endpoint
- Overall Survival (OS)
Study Overview
Brief Summary
This open-label, randomized, multicenter study will evaluate the efficacy and safety of bevacizumab (Avastin) in combination with standard of care (SOC) treatment in participants with advanced non-squamous NSCLC. Participants will be enrolled at documentation of progression of disease (PD) after 4-6 cycles of first-line treatment with bevacizumab plus a platinum doublet-containing therapy and a minimum of two cycles of bevacizumab maintenance treatment prior to PD. Participants will be randomly assigned to one of two treatment arms to receive either bevacizumab plus SOC treatment or SOC treatment alone.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically or cytologically confirmed non-squamous NSCLC
- •Documented progression of disease (locally recurrent or metastatic) per investigator assessment following first-line treatment with 4-6 cycles of Bevacizumab plus a platinum doublet-containing chemotherapy regimen and a minimum of 2 cycles of Bevacizumab (monotherapy) maintenance treatment prior to first progression of disease
- •No treatment interruption of Bevacizumab treatment greater than 2 consecutive cycles (42 days) between the start of first-line treatment to start of Cycle 1 of second line treatment
- •Randomization within 4 weeks of progression of disease
- •At least one unidimensionally measurable lesion meeting RECIST v1.1 criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Participants with adequate hematological, liver, and renal function
- •Female participants must not be pregnant or breast-feeding. Female participants of childbearing potential and fertile male participants must agree to use a highly effective contraceptive during the trial and for a period of at least 6 months following the last administration of trial drug(s)
Exclusion Criteria
- •Mixed, non-small cell and small cell tumors or mixed adenosquamous carcinomas with a predominant squamous component
- •Epidermal growth factor receptor (EGFR)-mutation-positive disease according to local laboratory testing
- •History of hemoptysis greater than or equal to (>/=) grade 2 within 3 months of randomization
- •History or evidence of inherited bleeding diathesis or coagulopathy with a risk of bleeding and active gastrointestinal bleeding
- •Major cardiac disease
- •Treatment with any other investigational agent within 28 days prior to randomization
- •Known hypersensitivity to bevacizumab or any of its excipients, or any SOC drugs foreseen
- •Malignancy other than NSCLC within 5 years prior to randomization and evidence of any other disease that contraindicates the use of an investigational or SOC drug
Arms & Interventions
Bevacizumab + Standard of Care
Participants will receive bevacizumab on Day 1 of every 21-days cycle along with standard of care (Erlotinib or Docetaxel or Pemetrexed) as second line treatment, until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).
Intervention: Bevacizumab (Drug)
Bevacizumab + Standard of Care
Participants will receive bevacizumab on Day 1 of every 21-days cycle along with standard of care (Erlotinib or Docetaxel or Pemetrexed) as second line treatment, until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).
Intervention: Docetaxel (Drug)
Bevacizumab + Standard of Care
Participants will receive bevacizumab on Day 1 of every 21-days cycle along with standard of care (Erlotinib or Docetaxel or Pemetrexed) as second line treatment, until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).
Intervention: Erlotinib (Drug)
Bevacizumab + Standard of Care
Participants will receive bevacizumab on Day 1 of every 21-days cycle along with standard of care (Erlotinib or Docetaxel or Pemetrexed) as second line treatment, until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).
Intervention: Pemetrexed (Drug)
Standard of Care
Participants will receive investigator's choice of standard of care (Erlotinib or Docetaxel or Pemetrexed) according to local practice until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).
Intervention: Docetaxel (Drug)
Standard of Care
Participants will receive investigator's choice of standard of care (Erlotinib or Docetaxel or Pemetrexed) according to local practice until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).
Intervention: Erlotinib (Drug)
Standard of Care
Participants will receive investigator's choice of standard of care (Erlotinib or Docetaxel or Pemetrexed) according to local practice until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).
Intervention: Pemetrexed (Drug)
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: Up to data cut-off date 24 June 2016 (approximately 5 years)
Overall survival (OS) was defined as the time from the date of randomization at first progression of disease to the date of death, regardless of the cause of death.
Secondary Outcomes
- Percentage of Participants With Objective Response According to RECIST v1.1(Up to data cut-off date 24 June 2016 (approximately 5 years))
- Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)(Up to data cut-off date 24 June 2016 (approximately 5 years))
- Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to data cut-off date 24 June 2016 (approximately 5 years))
- Time to Progression (TTP) According to RECIST v1.1(Up to data cut-off date 24 June 2016 (approximately 5 years))
- Percentage of Participants Who Are Alive at Month 6, 12, and 18(Month 6, 12, 18)
- Percentage of Participants With Disease Control According to RECIST v1.1(Up to data cut-off date 24 June 2016 (approximately 5 years))
- Duration of Response (DoR) According to RECIST v1.1(Up to data cut-off date 24 June 2016 (approximately 5 years))