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

Colorectal Neoplasms Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02776683
• Other study ID #: 1302.3
• Secondary ID: 2015-003718-25
• Status: Completed
• Phase: Phase 3
• Start date: June 8, 2016
• Est. completion date: October 3, 2018

Study information

• Verified date: October 2019
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: October 3, 2018
• Est. primary completion date: October 3, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Neoplasms

Intervention

Drug:
• BI 695502

• Avastin

Locations

Country	Name	City	State
Japan	Chiba Cancer Center	Chiba, Chiba
Japan	National Hospital Organization Shikoku Cancer Center	Ehime, Matsuyama
Japan	Hokkaido University Hospital	Hokkaido, Sapporo
Japan	Japan Organization of Occupational Health and Safety Kansai Rosai Hospital	Hyogo, Amagasaki
Japan	Kagawa University Hospital	Kagawa, Kita-gun
Japan	Osaka University Hospital	Osaka, Suita
Japan	Jananese Foundation for Cancer Research	Tokyo, Koto-ku
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Duran i Reynals	L'Hospitalet de Llobregat
Spain	Hospital Clínico de Valencia	Valencia
Ukraine	CI Chernivtsi RC Oncological Dispensary Bukovinian SMU	Chernivtsi
Ukraine	Munic.Instit."City Clin.Hosp.#4" of Dnipro City Council	Dnipropetrovsk
Ukraine	Regional Clinical Oncological Dispensary, Ivano-Frankivsk	Ivano-Frankivsk
Ukraine	CI of PH Kharkiv CCH #2	Kharkiv
Ukraine	Treatment-Diagnostic CTR of Private Enterprise, Kirovohrad	Kirovohrad
Ukraine	CI Kryvyi Rih Oncological Dispensary of DRC	Kryvyi Rih, Dnipropetrovsk
Ukraine	National Institute of Cancer	Kyiv
Ukraine	CI of LRC Lviv Onco.Reg.Treat.&Diag.Cent.	Lviv
Ukraine	Poltava Regional Clinical Oncological Dispensary, Poltava	Poltava
Ukraine	Sumy Regional Oncology Center	Sumy
Ukraine	Vinnytsia Regional Clinical Oncological Dispensary	Vinnytsia
United States	Texas Oncology, P.A.	Abilene	Texas
United States	Texas Oncology, PA,	Amarillo	Texas
United States	Pacific Cancer Medical Center, Inc.	Anaheim	California
United States	The Oncology Institute of Hope and Innovation	Anaheim	California
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Ashland Bellefonte Cancer Center	Ashland	Kentucky
United States	Texas Oncology, P.A.	Austin	Texas
United States	Aultman Hospital	Canton	Ohio
United States	Oncology Hematology Care	Cincinnati	Ohio
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	Texas Oncology, P.A.	Flower Mound	Texas
United States	Texas Oncology, P.A.	Garland	Texas
United States	Oncology Consultants, P.A.	Houston	Texas
United States	Texas Oncology, P.A.	McAllen	Texas
United States	Texas Oncology, PA	Mesquite	Texas
United States	Mayo Clinic-Arizona	Phoenix	Arizona
United States	Northwest Cancer Specialists PC	Portland	Oregon
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Texas Oncology San Antonio Medical Center	San Antonio	Texas
United States	Texas Oncology-San Antonio Northeast	San Antonio	Texas
United States	Willamette Valley Cancer Institute and Research Center	Springfield	Oregon
United States	Texas Oncology, P.A.	Tyler	Texas
United States	Tyler Hematology-Oncology, PA	Tyler	Texas
United States	Texas Oncology, P.A., Deke Slayton Cancer Center	Webster	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Japan,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	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.	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).
Secondary	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.	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).
Secondary	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.	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).
Secondary	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.	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).
Secondary	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.	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).

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