Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

BI 695502

Avastin

Boehringer Ingelheim

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®.

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

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

ORR was defined as the percentage of patients who achieved at least one visit response of complete response (CR) or partial response (PR) after the start of treatment. The response criteria evaluation was carried out according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. CR and PR did not need to be confirmed by a subsequent tumor assessment due to blinded central assessment. CR: Disappearance of all target lesions since baseline; PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Tumor assessments were performed prior to trial drug administration, until 18 weeks.

The following selected adverse events (AEs) were evaluated for comparability assessment of BI 695502 and US-licensed Avastin®:

* Infusion reactions (anaphylactic/hypersensitivity/infusion-related reactions),
* Thromboembolic events (arterial or venous),
* Febrile neutropenia,
* Gastrointestinal perforations,
* Hypertension,
* Proteinuria,
* Pulmonary hemorrhage,
* Other hemorrhages (not including pulmonary hemorrhages),
* Wound-healing complications/abscess/fistulas. The analysis of AEs was based on the concept of TEAEs. For non-switched patients, all AEs that started or worsened in severity on or after the first dose of trial drug and prior to the date of last administration of trial medication + 16 weeks inclusive were defined as TEAEs.

PFS was defined as the time from randomization until disease progression as determined by Investigator assessment or death from any cause, whichever occurred first during the pre-switch period. Disease progression was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 millimeters. Tumor assessments were performed prior to trial drug administration. PFS was calculated using the Kaplan-Meier technique.

OS was defined as the time randomization until death from any cause during the pre-switch period. OS was calculated using the Kaplan-Meier technique.

DOR was the time from first documented CR or PR until time of progression as determined by Investigator assessment during the pre-switch period. Tumor assessments were performed prior to trial drug administration. DOR was calculated using the Kaplan-Meier technique.

Patients received BI 695502 solution for i.v. infusion, 15 mg/kg bw, every 3 weeks for up to 6 cycles. During the induction cycles, patients also received standard combination chemotherapy consisting of paclitaxel 200 mg/m\^2 BSA, followed by carboplatin target AUC 6 mg/mL\*min, with adequate pre- and concomitant medication. After Cycle 4 to 6, for responding or stabilized patients, maintenance treatment with BI 695502 monotherapy could be started per the original randomization. Patients then received BI 695502 as a single agent until disease progression, death, withdrawal of consent, unacceptable toxicity, or until the Switch Visit (when each patient was switched to receive commercially available Avastin®), whichever occurred earlier.

BI 695502 (Pre-switch)

Patients received US-licensed Avastin® solution for i.v. infusion, 15 mg/kg bw, every 3 weeks for up to 6 cycles.

During the induction cycles, patients also received standard combination chemotherapy consisting of paclitaxel 200 mg/m\^2 BSA, followed by carboplatin target AUC 6 mg/mL\*min, with adequate pre- and concomitant medication. After Cycle 4 to 6, for responding or stabilized patients, maintenance treatment with US-licensed Avastin® monotherapy could be started per the original randomization. Patients then received US-licensed Avastin® as a single agent until disease progression, death, withdrawal of consent, unacceptable toxicity, or until the Switch Visit (when each patient was switched to receive commercially available Avastin®), whichever occurred earlier.

US-licensed Avastin® (Pre-switch)

Patients switched from BI 695502 to receive commercially available Avastin®.

BI 695502 (Post-switch)

Patients switched from US-licensed Avastin® to receive commercially available Avastin®.

US-licensed Avastin® (Post-switch)

Patients received BI 695502 solution for i.v. infusion, 15 mg/kg bw, every 3 weeks for up to 6 cycles. During the induction cycles, patients also received standard combination chemotherapy consisting of paclitaxel 200 mg/m\^2 body surface area (BSA), followed by carboplatin target area under the curve (AUC) 6 mg/mL\*min, with adequate pre- and concomitant medication. After Cycle 4 to 6, for responding or stabilized patients, maintenance treatment with BI 695502 monotherapy could be started per the original randomization. Patients then received BI 695502 as a single agent until disease progression, death, withdrawal of consent, unacceptable toxicity, or until the Switch Visit (when each patient was switched to receive commercially available Avastin®), whichever occurred earlier.

Patients received US-licensed Avastin® solution for i.v. infusion, 15 mg/kg bw, every 3 weeks for up to 6 cycles. During the induction cycles, patients also received standard combination chemotherapy consisting of paclitaxel 200 mg/m\^2 BSA, followed by carboplatin target AUC 6 mg/mL\*min, with adequate pre- and concomitant medication.

After Cycle 4 to 6, for responding or stabilized patients, maintenance treatment with US-licensed Avastin® monotherapy could be started per the original randomization. Patients then received US-licensed Avastin® as a single agent until disease progression, death, withdrawal of consent, unacceptable toxicity, or until the Switch Visit (when each patient was switched to receive commercially available Avastin®), whichever occurred earlier.

Avastin® US

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Full Analysis Set (FAS): The FAS contained all randomized patients who received at least 1 dose of trial drug and who had a baseline tumor assessment.

From 21 December 2017, after Week 18 primary analysis data cut-off, the Sponsor recommended to switch patients from BI 695502/US-licensed Avastin® to Avastin®. The main analyses to report all endpoint and AE results was the pre-switch period.

Boehringer Ingelheim, Call Centre

Analysis was based on a log-binomial regression model with subsequent transformation of the estimated parameter (ratio of best ORR) respective CIs to the ratio scale. The model included the following explanatory variables: treatment, sex (male versus female), smoking status (never smoked versus current/ex-smoker), NSCLC stage (recurrent versus Stage IV) and ethnicity (East Asian origin versus Non-East Asian).

The FAS contained all randomized patients who received at least 1 dose of trial drug and who had a baseline tumor assessment. Best ORR (CR+PR) is reported for observed values.

Best Overall Response Rate (ORR), Based on Unconfirmed Response Assessment, as Assessed by Central Imaging Review Until 18 Weeks After the Start of Treatment

At least 1 AE selected for comparability assessment, risk ratio X (BI 695502) versus Y (US-licensed Avastin®) was defined as (a/(a+b))/(c/(c+d)), where 'a' was the number of patients with TEAEs selected for comparability within treatment group X, 'a+b' was the total number of patients in treatment group X, 'c' was the number of patients with TEAEs selected for comparability within treatment group Y and 'c+d' was the total number of patients in treatment group Y.

Infusion reactions, risk ratio X (BI 695502) versus Y (US-licensed Avastin®) was defined as (a/(a+b))/(c/(c+d)), where 'a' was the number of patients with TEAEs selected for comparability within treatment group X, 'a+b' was the total number of patients in treatment group X, 'c' was the number of patients with TEAEs selected for comparability within treatment group Y and 'c+d' was the total number of patients in treatment group Y.

Thromboembolic events, risk ratio X (BI 695502) versus Y (US-licensed Avastin®) was defined as (a/(a+b))/(c/(c+d)), where 'a' was the number of patients with TEAEs selected for comparability within treatment group X, 'a+b' was the total number of patients in treatment group X, 'c' was the number of patients with TEAEs selected for comparability within treatment group Y and 'c+d' was the total number of patients in treatment group Y.

Febrile neutropenia, risk ratio X (BI 695502) versus Y (US-licensed Avastin®) was defined as (a/(a+b))/(c/(c+d)), where 'a' was the number of patients with TEAEs selected for comparability within treatment group X, 'a+b' was the total number of patients in treatment group X, 'c' was the number of patients with TEAEs selected for comparability within treatment group Y and 'c+d' was the total number of patients in treatment group Y.

Gastrointestinal perforations, risk ratio X (BI 695502) versus Y (US-licensed Avastin®) was defined as (a/(a+b))/(c/(c+d)), where 'a' was the number of patients with TEAEs selected for comparability within treatment group X, 'a+b' was the total number of patients in treatment group X, 'c' was the number of patients with TEAEs selected for comparability within treatment group Y and 'c+d' was the total number of patients in treatment group Y.

Hypertension, risk ratio X (BI 695502) versus Y (US-licensed Avastin®) was defined as (a/(a+b))/(c/(c+d)), where 'a' was the number of patients with TEAEs selected for comparability within treatment group X, 'a+b' was the total number of patients in treatment group X, 'c' was the number of patients with TEAEs selected for comparability within treatment group Y and 'c+d' was the total number of patients in treatment group Y.

Proteinuria, risk ratio X (BI 695502) versus Y (US-licensed Avastin®) was defined as (a/(a+b))/(c/(c+d)), where 'a' was the number of patients with TEAEs selected for comparability within treatment group X, 'a+b' was the total number of patients in treatment group X, 'c' was the number of patients with TEAEs selected for comparability within treatment group Y and 'c+d' was the total number of patients in treatment group Y.

Pulmonary haemorrhage, risk ratio X (BI 695502) versus Y (US-licensed Avastin®) was defined as (a/(a+b))/(c/(c+d)), where 'a' was the number of patients with TEAEs selected for comparability within treatment group X, 'a+b' was the total number of patients in treatment group X, 'c' was the number of patients with TEAEs selected for comparability within treatment group Y and 'c+d' was the total number of patients in treatment group Y.

Other hemorrhages, risk ratio X (BI 695502) versus Y (US-licensed Avastin®) was defined as (a/(a+b))/(c/(c+d)), where 'a' was the number of patients with TEAEs selected for comparability within treatment group X, 'a+b' was the total number of patients in treatment group X, 'c' was the number of patients with TEAEs selected for comparability within treatment group Y and 'c+d' was the total number of patients in treatment group Y.

Wound healing complications/ abscesses/ fistulas, risk ratio X (BI 695502) versus Y (US-licensed Avastin®) was defined as (a/(a+b))/(c/(c+d)), where 'a' was the number of patients with TEAEs selected for comparability within treatment group X, 'a+b' was the total number of patients in treatment group X, 'c' was the number of patients with TEAEs selected for comparability within treatment group Y and 'c+d' was the total number of patients in treatment group Y.

AtLeast 1 AE selected for Comparability Assessment

Infusion reactions

Thromboembolic events

Febrile neutropenia

Gastrointestinal perforations

Hypertension

Proteinuria

Pulmonary haemorrhage

Other hemorrhages

Wound-healing complications/abscess/fistulas

The Treated Set contained all patients who signed informed consent and who received at least one dose of trial drug.

Percentage of Patients With Selected Treatment-Emergent Adverse Events (TEAEs) For Comparability Assessment of BI 695502 and US-licensed Avastin®

Analysis based on a Cox-proportional hazards regression model. The model included the following explanatory variables: treatment, sex (male versus female), smoking status (never smoked versus current/ex-smoker), NSCLC stage (recurrent versus Stage IV) and ethnicity (East Asian origin versus non East Asian).

The Full Analysis Set (FAS) contained all randomized patients who received at least 1 dose of trial drug and who had a baseline tumor assessment.

Progression-Free Survival (PFS) Time as Determined by Investigator Assessment

The FAS contained all randomized patients who received at least 1 dose of trial drug and who had a baseline tumor assessment.

Overall Survival (OS) Time

The FAS contained all randomized patients who received at least 1 dose of trial drug and who had a baseline tumor assessment. Only patients with an objective response were included in the analysis.

Duration of Response (DOR) as Determined by Investigator Assessment

Randomized Through Treatment Start

Pre-switch Period

Post-switch Period

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

The objective of this trial is to evaluate the safety and tolerability of BI 695502 in combination with leucovorin/5-fluorouracil/oxaliplatin (mFOLFOX6) and as maintenance therapy (when applicable). As well as to evaluate the following efficacy parameters: Progression-free survival (PFS), objective response rate (proportion of patients with complete response \[CR\] plus partial response \[PR\]), overall survival (OS), duration of response (DOR), time to progression (TTP).

Open-label, Single Arm Trial of BI 695502 in Patients With Previously Untreated Metastatic Colorectal Cancer

A Single Arm, Open-label, Multicenter, Multinational, Safety and Efficacy Phase IIIb Trial of BI 695502 Plus mFOLFOX6 in Patients With Previously Untreated Metastatic Colorectal Cancer

The primary safety endpoint of the trial was patients with any of the following selected adverse events (AEs):

* Infusion reactions (anaphylactic/hypersensitivity/infusion-related reactions),
* Thromboembolic events (arterial or venous),
* Gastrointestinal perforations,
* Hypertension,
* Proteinuria,
* Pulmonary hemorrhage
* All hemorrhages (including pulmonary hemorrhages)
* Wound-healing complications/abscess/fistulas
* Posterior reversible encephalopathy syndrome
* Ovarian failure. All AEs with an onset between start of treatment and end of the residual effect period (REP), a period of 18 weeks after the last dose of trial medication were considered for the primary safety analysis. Confidence interval was calculated using Wilson score method.

DOR was the time from first documented Complete Response (CR) (CR is disappearance of all target lesions) or Partial Response (PR) (PR is at least a 30% decrease in the sum of diameters (SoD) of target lesions taking as reference the baseline sum diameters) until time of progression as assessed by central imaging review per Response evaluation criteria in solid tumors (RECIST) 1.1. RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize") or worsen ("progress") during treatment. DOR was calculated using the Kaplan-Meier technique. Confidence interval was calculated based on the Brookmeyer and Crowley method.

TTP was defined as the time from first administration of trial medication to the date of tumor progression as assessed by central imaging review per RECIST 1.1 (RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize") or worsen ("progress") during treatment.). TTP was calculated using the Kaplan-Meier technique. Confidence interval was calculated based on the Brookmeyer and Crowley method.

OR rate was defined as the percentage of patients who achieved at least one visit response of CR (CR is disappearance of all target lesions) or PR (PR is at least a 30% decrease in the sum of diameters (SoD) of target lesions taking as reference the baseline sum diameters) after the start of treatment. The response criteria evaluation was carried out according to RECIST 1.1. RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize") or worsen ("progress") during treatment. Confidence interval was calculated using Wilson score method. The definition for OR (CR/PR) extends until disease progression/ death/ unacceptable toxicity/ end of the trial, whichever occurred earlier. However for "Duration of response" this censoring does not apply. Hence the apparent discrepancy.

OR = CR + PR.

OS was defined as the time from first administration of trial medication until death from any cause. OS was calculated using the Kaplan-Meier technique. Confidence interval was calculated based on the Brookmeyer and Crowley method.

PFS was defined as the time from first administration of trial medication until disease progression as assessed by central imaging review or death due to any cause. Disease progression was assessed according to RECIST 1.1. RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize") or worsen ("progress") during treatment. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. PFS was calculated using the Kaplan-Meier technique. Confidence interval was calculated based on the Brookmeyer and Crowley method.

All-Cause mortality is defined as death due to any cause (including disease progression) and is reported for the overall study period, including both the pre-switch period for BI 695502 treatment and post-switch period for Avastin® treatment. Serious and other (non-serious) data is based on on-treatment adverse events.

All patients were to receive BI 695502 (5 milligrams per kilogram \[mg/kg\]) solution for intravenous (i.v.) infusion in combination with mFOLFOX6 chemotherapy every 2 weeks. Patients were to continue to receive treatment during the pre-switch period until disease progression, death, unacceptable toxicity, or the end of the trial, whichever occurred earlier. Based on patient tolerability, at least 8 cycles of mFOLFOX6 were to be given to all patients.

Treated set (TS): The TS contained all participants who signed informed consent and who received at least one dose of trial medication.

From 21 December 2017, the Sponsor recommended for patients to be switched from BI 695502 to Avastin®. The main analyses for reporting primary and secondary endpoints was clarified as the pre-switch period (i.e., all receiving BI 695502).

Patients with any of the selected AEs

Pulmonary Haemorrhage

Hemorrhages

Wound-healing complications

Reversible Encephalopathy Syndrome

Ovarian failure

Treated set (TS): The TS contained all patients who signed informed consent and who received at least one dose of trial medication.

Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs) in the Specified Categories Selected for Primary Endpoint Assessment

TS: The TS contained all patients who signed informed consent and who received at least one dose of trial medication. Only patients with complete or partial objective response were included in the analysis.

Duration of Response (DOR) as Assessed by Central Imaging Review

TS: The TS contained all patients who signed informed consent and who received at least one dose of trial medication.

Time to Progression (TTP) as Assessed by Central Imaging Review

Objective Response (OR) Rate as Assessed by Central Imaging Review

Progression-Free Survival (PFS) Time as Assessed by Central Imaging Review

At the switch visit, patients were to be switched from BI 695502 to Avastin®. Post-switch, patients were to receive Avastin® (5 mg/kg) solution for i.v. infusion in combination with mFOLFOX6 chemotherapy every 2 weeks. Patients were to continue to receive treatment until disease progression, death, unacceptable toxicity, or the end of the trial, whichever occurred earlier.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase III Trial BI 695502 Plus Chemotherapy vs. Avastin® Plus Chemotherapy in Patients With Lung Cancer	NCT02272413	Carcinoma, Non-...	BI 695502 Avastin	18 Years -	Boehringer Ingelheim
Phase III Trial BI 695502 Plus Chemotherapy vs. Avastin® Plus Chemotherapy in Patients With Lung Cancer	NCT02272413	Carcinoma, Non-...	BI 695502 Avastin	18 Years -	Boehringer Ingelheim
Open-label, Single Arm Trial of BI 695502 in Patients With Previously Untreated Metastatic Colorectal Cancer	NCT02776683	Colorectal Neop...	BI 695502 Avastin	18 Years -	Boehringer Ingelheim
Open-label, Single Arm Trial of BI 695502 in Patients With Previously Untreated Metastatic Colorectal Cancer	NCT02776683	Colorectal Neop...	BI 695502 Avastin	18 Years -	Boehringer Ingelheim

Spots Global Cancer Trial Database for bi 695502

Every month we try and update this database with for bi 695502 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for bi 695502

Every month we try and update this database with for bi 695502 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for bi 695502 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.