Back to resultsOpen-label, Single Arm Trial of BI 695502 in Patients With Previously Untreated Metastatic Colorectal Cancer (INVICTAN®-3)
Primary Purpose
Colorectal Neoplasms
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
BI 695502
Avastin
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Neoplasms
Eligibility Criteria
Inclusion criteria:
- Males and females aged >=18 years (for Japan only: Age >=20 years at time of signing Informed Consent Form) with histologically confirmed metastatic colorectal cancer (mCRC).
- Metastatic disease not amenable to surgical curative treatment and eligible to receive therapy with mFOLFOX6 (Leucovorin/5-Fluorouracil/Oxaliplatin) + bevacizumab.
- At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
- Adequate hepatic, renal and bone marrow function.
- Further inclusion criteria apply.
Exclusion criteria:
- Prior systemic therapy for metastatic disease
- Prior therapy with monoclonal antibodies or small molecule inhibitors against Vascular endothelial growth factor (VEGF) or VEGF receptors, including Avastin® or Avastin® biosimilar
- Previous malignancy other than Colorectal cancer (CRC) in the last 5 years except for basal cell cancer of the skin or pre-invasive cancer of the cervix
- Spinal cord compression or brain metastases unless asymptomatic, stable and not requiring steroids for at least 6 weeks prior to start of study treatment
- 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
- A thrombotic or hemorrhagic event <=6 months prior to screening (includes hemoptysis, Gastrointestinal (GI) bleeding, hematemesis, central nervous system hemorrhage, epistaxis, vaginal bleeding, cerebral infarction, transient ischemic attacks, myocardial infarction, angina, and coronary artery disease)
- Further exclusion criteria apply
Sites / Locations
- Mayo Clinic-Arizona
- Pacific Cancer Medical Center, Inc.
- The Oncology Institute of Hope and Innovation
- Rocky Mountain Cancer Centers
- Ashland Bellefonte Cancer Center
- University of Michigan Health System
- Washington University School of Medicine
- Aultman Hospital
- Oncology Hematology Care
- Northwest Cancer Specialists PC
- Willamette Valley Cancer Institute and Research Center
- Texas Oncology, P.A.
- Texas Oncology, PA,
- Texas Oncology, P.A.
- Texas Oncology, P.A.
- Texas Oncology, P.A.
- Oncology Consultants, P.A.
- Texas Oncology, P.A.
- Texas Oncology, PA
- Texas Oncology-San Antonio Northeast
- Texas Oncology San Antonio Medical Center
- Tyler Hematology-Oncology, PA
- Texas Oncology, P.A.
- Texas Oncology, P.A., Deke Slayton Cancer Center
- Virginia Cancer Institute
- Chiba Cancer Center
- National Hospital Organization Shikoku Cancer Center
- Hokkaido University Hospital
- Japan Organization of Occupational Health and Safety Kansai Rosai Hospital
- Kagawa University Hospital
- Osaka University Hospital
- Jananese Foundation for Cancer Research
- Hospital Vall d'Hebron
- Hospital Duran i Reynals
- Hospital Clínico de Valencia
- CI Chernivtsi RC Oncological Dispensary Bukovinian SMU
- Munic.Instit."City Clin.Hosp.#4" of Dnipro City Council
- Regional Clinical Oncological Dispensary, Ivano-Frankivsk
- CI of PH Kharkiv CCH #2
- Treatment-Diagnostic CTR of Private Enterprise, Kirovohrad
- CI Kryvyi Rih Oncological Dispensary of DRC
- National Institute of Cancer
- CI of LRC Lviv Onco.Reg.Treat.&Diag.Cent.
- Poltava Regional Clinical Oncological Dispensary, Poltava
- Sumy Regional Oncology Center
- Vinnytsia Regional Clinical Oncological Dispensary
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
All patients
Arm Description
Outcomes
Primary Outcome Measures
Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs) in the Specified Categories Selected for Primary Endpoint Assessment
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.
Secondary Outcome Measures
Duration of Response (DOR) as Assessed by Central Imaging Review
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.
Time to Progression (TTP) as Assessed by Central Imaging Review
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.
Objective Response (OR) Rate as Assessed by Central Imaging Review
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.
Overall Survival (OS) Time
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.
Progression-Free Survival (PFS) Time as Assessed by Central Imaging Review
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02776683
Brief Title
Open-label, Single Arm Trial of BI 695502 in Patients With Previously Untreated Metastatic Colorectal Cancer
Acronym
INVICTAN®-3
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
June 8, 2016 (Actual)
Primary Completion Date
October 3, 2018 (Actual)
Study Completion Date
October 3, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
Brief Summary
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
123 (Actual)
8. Arms, Groups, and Interventions
Arm Title
All patients
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
BI 695502
Intervention Type
Drug
Intervention Name(s)
Avastin
Primary Outcome Measure Information:
Title
Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs) in the Specified Categories Selected for Primary Endpoint Assessment
Description
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.
Time Frame
From baseline up to 18 weeks after the last dose of trial medication prior to the Switch Visit. Maximum duration of up to 32 treatment cycles + safety follow up (up to 82 weeks overall).
Secondary Outcome Measure Information:
Title
Duration of Response (DOR) as Assessed by Central Imaging Review
Description
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.
Time Frame
Tumor scans were performed at baseline then every ~8 weeks up to 34 weeks, then every ~12 weeks thereafter until confirmed disease progression. Analysis performed for the pre-switch period only; maximum duration of up to 32 treatment cycles (64 weeks).
Title
Time to Progression (TTP) as Assessed by Central Imaging Review
Description
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.
Time Frame
Tumor scans were performed at baseline then every ~8 weeks up to 34 weeks, then every ~12 weeks thereafter until confirmed disease progression. Analysis performed for the pre-switch period only; maximum duration of up to 32 treatment cycles (64 weeks).
Title
Objective Response (OR) Rate as Assessed by Central Imaging Review
Description
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.
Time Frame
Tumor scans were performed at baseline then every ~8 weeks up to 34 weeks, then every ~12 weeks thereafter until confirmed disease progression. Analysis performed for the pre-switch period only; maximum duration of up to 32 treatment cycles (64 weeks).
Title
Overall Survival (OS) Time
Description
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.
Time Frame
From date of first dose of trial medication until last date of trial medication + 18 weeks (REP), up to a maximum of 32 treatment cycles + safety follow up (up to 82 weeks overall).
Title
Progression-Free Survival (PFS) Time as Assessed by Central Imaging Review
Description
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.
Time Frame
Tumor scans were performed at baseline then every ~8 weeks up to 34 weeks, then every ~12 weeks thereafter until confirmed disease progression. Analysis performed for the pre-switch period only; maximum duration of up to 32 treatment cycles (64 weeks).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Males and females aged >=18 years (for Japan only: Age >=20 years at time of signing Informed Consent Form) with histologically confirmed metastatic colorectal cancer (mCRC).
Metastatic disease not amenable to surgical curative treatment and eligible to receive therapy with mFOLFOX6 (Leucovorin/5-Fluorouracil/Oxaliplatin) + bevacizumab.
At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
Adequate hepatic, renal and bone marrow function.
Further inclusion criteria apply.
Exclusion criteria:
Prior systemic therapy for metastatic disease
Prior therapy with monoclonal antibodies or small molecule inhibitors against Vascular endothelial growth factor (VEGF) or VEGF receptors, including Avastin® or Avastin® biosimilar
Previous malignancy other than Colorectal cancer (CRC) in the last 5 years except for basal cell cancer of the skin or pre-invasive cancer of the cervix
Spinal cord compression or brain metastases unless asymptomatic, stable and not requiring steroids for at least 6 weeks prior to start of study treatment
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
A thrombotic or hemorrhagic event <=6 months prior to screening (includes hemoptysis, Gastrointestinal (GI) bleeding, hematemesis, central nervous system hemorrhage, epistaxis, vaginal bleeding, cerebral infarction, transient ischemic attacks, myocardial infarction, angina, and coronary artery disease)
Further exclusion criteria apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Organizational Affiliation
Boehringer Ingelheim
Official's Role
Study Chair
Facility Information:
Facility Name
Mayo Clinic-Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
Pacific Cancer Medical Center, Inc.
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
The Oncology Institute of Hope and Innovation
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Ashland Bellefonte Cancer Center
City
Ashland
State/Province
Kentucky
ZIP/Postal Code
41101
Country
United States
Facility Name
University of Michigan Health System
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Aultman Hospital
City
Canton
State/Province
Ohio
ZIP/Postal Code
44710
Country
United States
Facility Name
Oncology Hematology Care
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States
Facility Name
Northwest Cancer Specialists PC
City
Portland
State/Province
Oregon
ZIP/Postal Code
97225
Country
United States
Facility Name
Willamette Valley Cancer Institute and Research Center
City
Springfield
State/Province
Oregon
ZIP/Postal Code
97477
Country
United States
Facility Name
Texas Oncology, P.A.
City
Abilene
State/Province
Texas
ZIP/Postal Code
79606
Country
United States
Facility Name
Texas Oncology, PA,
City
Amarillo
State/Province
Texas
ZIP/Postal Code
79106
Country
United States
Facility Name
Texas Oncology, P.A.
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
Texas Oncology, P.A.
City
Flower Mound
State/Province
Texas
ZIP/Postal Code
75028
Country
United States
Facility Name
Texas Oncology, P.A.
City
Garland
State/Province
Texas
ZIP/Postal Code
75042-5788
Country
United States
Facility Name
Oncology Consultants, P.A.
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Texas Oncology, P.A.
City
McAllen
State/Province
Texas
ZIP/Postal Code
78503-1298
Country
United States
Facility Name
Texas Oncology, PA
City
Mesquite
State/Province
Texas
ZIP/Postal Code
75150
Country
United States
Facility Name
Texas Oncology-San Antonio Northeast
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78217
Country
United States
Facility Name
Texas Oncology San Antonio Medical Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Tyler Hematology-Oncology, PA
City
Tyler
State/Province
Texas
ZIP/Postal Code
75701
Country
United States
Facility Name
Texas Oncology, P.A.
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
Texas Oncology, P.A., Deke Slayton Cancer Center
City
Webster
State/Province
Texas
ZIP/Postal Code
77598
Country
United States
Facility Name
Virginia Cancer Institute
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23226
Country
United States
Facility Name
Chiba Cancer Center
City
Chiba, Chiba
ZIP/Postal Code
260-8717
Country
Japan
Facility Name
National Hospital Organization Shikoku Cancer Center
City
Ehime, Matsuyama
ZIP/Postal Code
791-0280
Country
Japan
Facility Name
Hokkaido University Hospital
City
Hokkaido, Sapporo
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
Japan Organization of Occupational Health and Safety Kansai Rosai Hospital
City
Hyogo, Amagasaki
ZIP/Postal Code
660-8511
Country
Japan
Facility Name
Kagawa University Hospital
City
Kagawa, Kita-gun
ZIP/Postal Code
761-0793
Country
Japan
Facility Name
Osaka University Hospital
City
Osaka, Suita
ZIP/Postal Code
565-0871
Country
Japan
Facility Name
Jananese Foundation for Cancer Research
City
Tokyo, Koto-ku
ZIP/Postal Code
135-8550
Country
Japan
Facility Name
Hospital Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Duran i Reynals
City
L'Hospitalet de Llobregat
ZIP/Postal Code
08907
Country
Spain
Facility Name
Hospital Clínico de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
CI Chernivtsi RC Oncological Dispensary Bukovinian SMU
City
Chernivtsi
ZIP/Postal Code
58013
Country
Ukraine
Facility Name
Munic.Instit."City Clin.Hosp.#4" of Dnipro City Council
City
Dnipropetrovsk
ZIP/Postal Code
49102
Country
Ukraine
Facility Name
Regional Clinical Oncological Dispensary, Ivano-Frankivsk
City
Ivano-Frankivsk
ZIP/Postal Code
76018
Country
Ukraine
Facility Name
CI of PH Kharkiv CCH #2
City
Kharkiv
ZIP/Postal Code
61037
Country
Ukraine
Facility Name
Treatment-Diagnostic CTR of Private Enterprise, Kirovohrad
City
Kirovohrad
ZIP/Postal Code
25006
Country
Ukraine
Facility Name
CI Kryvyi Rih Oncological Dispensary of DRC
City
Kryvyi Rih, Dnipropetrovsk
ZIP/Postal Code
50048
Country
Ukraine
Facility Name
National Institute of Cancer
City
Kyiv
ZIP/Postal Code
03022
Country
Ukraine
Facility Name
CI of LRC Lviv Onco.Reg.Treat.&Diag.Cent.
City
Lviv
ZIP/Postal Code
79031
Country
Ukraine
Facility Name
Poltava Regional Clinical Oncological Dispensary, Poltava
City
Poltava
ZIP/Postal Code
38011
Country
Ukraine
Facility Name
Sumy Regional Oncology Center
City
Sumy
ZIP/Postal Code
40022
Country
Ukraine
Facility Name
Vinnytsia Regional Clinical Oncological Dispensary
City
Vinnytsia
ZIP/Postal Code
21029
Country
Ukraine
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com/
Description
Related Info
Learn more about this trial
Open-label, Single Arm Trial of BI 695502 in Patients With Previously Untreated Metastatic Colorectal Cancer
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