Phase III Trial BI 695502 Plus Chemotherapy vs. Avastin® Plus Chemotherapy in Patients With Lung Cancer

• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Study Description

Brief Summary:

The objective of this phase III trial is to establish statistical equivalence in terms of efficacy (best overall response rate [ORR], proportion of patients with complete response [CR] plus partial response [PR]) until 18 weeks of first-line treatment with BI 695502 plus chemotherapy versus Avastin® plus chemotherapy followed by maintenance monotherapy with either BI 695502 or Avastin®.

Condition or disease	Intervention/treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: BI 695502; Drug: Avastin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 671 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind Phase III Trial to Evaluate Efficacy and Safety of BI 695502 Plus Chemotherapy Versus Avastin® Plus Chemotherapy in Patients With Advanced Nonsquamous Non-Small Cell Lung Cancer
• Actual Study Start Date: July 8, 2015
• Actual Primary Completion Date: June 30, 2017
• Actual Study Completion Date: November 16, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: BI 695502	Drug: BI 695502
Active Comparator: Avastin	Drug: Avastin

Outcome Measures

Primary Outcome Measures :

1. Best overall Response rate (ORR) based on unconfirmed response assessment as assessed by central imaging review until 18 weeks after the start of treatment. [ Time Frame: randomization until 18 weeks ]

Secondary Outcome Measures :

1. The proportion of patients with the especially selected adverse events for comparability assessment of BI 695502 and Avastin: Gastrointestinal perforations, Hypertension, Proteinuria, Pulmonary hemorrhage [ Time Frame: randomization until end of Safety follow up ]
2. The proportion of patients with the especially selected adverse events for comparability assessment of BI 695502 and Avastin: Other hemorrhages, Wound-healing complications/abscess/fistulas [ Time Frame: randomization until end of Safety follow up ]
3. Progression-free survival (PFS) defined as the time from randomization until disease progression as per investigator assessment or death. [ Time Frame: randomization until disease progression or death ]
4. Overall survival (OS) defined as the time from randomization until death from any cause. [ Time Frame: randomization until death ]
5. Proportion of patients with the especially selected adverse events (AEs) for comparability assessment of BI 695502 and Avastin®: Anaphylactic, Hypersensitivity, infusion-related reactions, arterial and venous thromboembolic events, febrile neutropenia [ Time Frame: randomization until end of Safety follow up ]
6. Duration of response defined as the time from first documented complete response (CR) plus partial response (PR) until time of progression as per investigator assessment. [ Time Frame: from first documented CR or PR until time of progression ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria:

Adult patients aged >=18 years with histologically or cytologically confirmed advanced nonsquamous non-small cell lung cancer (nsNSCLC). Mixed tumors should be categorized according to the predominant histology.

Note: NSCLC should be predominantly nonsquamous. Recurrent or metastatic disease (Stage IV) with an indication for therapy with paclitaxel + carboplatin + Avastin®.

Patients harboring tumors with unknown or without activating epidermal growth factor receptor (EGFR) / anaplastic lymphoma receptor tyrosine kinase (ALK) mutation maybe included provided chemotherapy is standard of care. At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 based on independent central review.

Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.

Adequate hepatic, renal, and bone marrow function:

Life expectancy > 6 months based on clinical judgment. Further inclusion criteria apply.

Exclusion criteria:

Prior therapy with monoclonal antibodies or small molecule inhibitors against Vascular Endothelial Growth Factor (VEGF) or VEGF receptors, including Avastin®.

Prior systemic therapy for metastatic disease. Prior systemic anticancer therapy or radiotherapy for locally advanced nsNSCLC if completed <12 months prior to Screening.

Previous malignancy other than NSCLC in the last 5 years except for basal cell cancer of the skin or pre-invasive cancer of the cervix.

Symptomatic brain metastasis. Diagnosis of small cell carcinoma of the lung, squamous cell carcinoma of the lung, NSCLC not specified (NS) or NSCLC not otherwise specified(NOS).

Any unresolved toxicity > Common Toxicity Criteria Grade 1 (except alopecia) from previous anticancer therapy (including radiotherapy).

History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding. Thrombotic or hemorrhagic event =< 6 months prior to Screening. Further exclusion criteria apply.

Contacts and Locations

  Show 189 Study Locations

Sponsors and Collaborators

Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

More Information

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT02272413 History of Changes
• Other Study ID Numbers: 1302.5; 2014-002161-30 ( EudraCT Number )
• First Posted: October 23, 2014
• Last Update Posted: November 26, 2018
• Last Verified: November 2018

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Bevacizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors