Open-label, Single Arm Trial of BI 695502 in Patients With Previously Untreated Metastatic Colorectal Cancer (INVICTAN®-3)

November 1, 2019 updated by: Boehringer Ingelheim

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 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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

123

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Chiba, Chiba, Japan, 260-8717
        • Chiba Cancer Center
      • Ehime, Matsuyama, Japan, 791-0280
        • National Hospital Organization Shikoku Cancer Center
      • Hokkaido, Sapporo, Japan, 060-8648
        • Hokkaido University Hospital
      • Hyogo, Amagasaki, Japan, 660-8511
        • Japan Organization of Occupational Health and Safety Kansai Rosai Hospital
      • Kagawa, Kita-gun, Japan, 761-0793
        • Kagawa University Hospital
      • Osaka, Suita, Japan, 565-0871
        • Osaka University Hospital
      • Tokyo, Koto-ku, Japan, 135-8550
        • Jananese Foundation for Cancer Research
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Vall d'Hebron
      • L'Hospitalet de Llobregat, Spain, 08907
        • Hospital Duran i Reynals
      • Valencia, Spain, 46010
        • Hospital Clinico de Valencia
  • Ukraine
      • Chernivtsi, Ukraine, 58013
        • CI Chernivtsi RC Oncological Dispensary Bukovinian SMU
      • Dnipropetrovsk, Ukraine, 49102
        • Munic.Instit."City Clin.Hosp.#4" of Dnipro City Council
      • Ivano-Frankivsk, Ukraine, 76018
        • Regional Clinical Oncological Dispensary, Ivano-Frankivsk
      • Kharkiv, Ukraine, 61037
        • CI of PH Kharkiv CCH #2
      • Kirovohrad, Ukraine, 25006
        • Treatment-Diagnostic CTR of Private Enterprise, Kirovohrad
      • Kryvyi Rih, Dnipropetrovsk, Ukraine, 50048
        • CI Kryvyi Rih Oncological Dispensary of DRC
      • Kyiv, Ukraine, 03022
        • National Institute of Cancer
      • Lviv, Ukraine, 79031
        • CI of LRC Lviv Onco.Reg.Treat.&Diag.Cent.
      • Poltava, Ukraine, 38011
        • Poltava Regional Clinical Oncological Dispensary, Poltava
      • Sumy, Ukraine, 40022
        • Sumy Regional Oncology Center
      • Vinnytsia, Ukraine, 21029
        • Vinnytsia Regional Clinical Oncological Dispensary
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic-Arizona
    • California
      • Anaheim, California, United States, 92801
        • Pacific Cancer Medical Center, Inc.
      • Anaheim, California, United States, 92801
        • The Oncology Institute of Hope and Innovation
    • Colorado
      • Denver, Colorado, United States, 80218
        • Rocky Mountain Cancer Centers
    • Kentucky
      • Ashland, Kentucky, United States, 41101
        • Ashland Bellefonte Cancer Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Health System
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Ohio
      • Canton, Ohio, United States, 44710
        • Aultman Hospital
      • Cincinnati, Ohio, United States, 45242
        • Oncology Hematology Care
    • Oregon
      • Portland, Oregon, United States, 97225
        • Northwest Cancer Specialists PC
      • Springfield, Oregon, United States, 97477
        • Willamette Valley Cancer Institute and Research Center
    • Texas
      • Abilene, Texas, United States, 79606
        • Texas Oncology, P.A.
      • Amarillo, Texas, United States, 79106
        • Texas Oncology, PA,
      • Austin, Texas, United States, 78705
        • Texas Oncology, P.A.
      • Flower Mound, Texas, United States, 75028
        • Texas Oncology, P.A.
      • Garland, Texas, United States, 75042-5788
        • Texas Oncology, P.A.
      • Houston, Texas, United States, 77030
        • Oncology Consultants, P.A.
      • McAllen, Texas, United States, 78503-1298
        • Texas Oncology, P.A.
      • Mesquite, Texas, United States, 75150
        • Texas Oncology, PA
      • San Antonio, Texas, United States, 78217
        • Texas Oncology-San Antonio Northeast
      • San Antonio, Texas, United States, 78229
        • Texas Oncology San Antonio Medical Center
      • Tyler, Texas, United States, 75702
        • Texas Oncology, P.A.
      • Tyler, Texas, United States, 75701
        • Tyler Hematology-Oncology, PA
      • Webster, Texas, United States, 77598
        • Texas Oncology, P.A., Deke Slayton Cancer Center
    • Virginia
      • Richmond, Virginia, United States, 23226
        • Virginia Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: All patients
Drug: Avastin
Drug: BI 695502

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs) in the Specified Categories Selected for Primary Endpoint Assessment
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).

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response (DOR) as Assessed by Central Imaging Review
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).
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).
Time to Progression (TTP) as Assessed by Central Imaging Review
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).
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).
Objective Response (OR) Rate as Assessed by Central Imaging Review
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).

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 8, 2016

Primary Completion (Actual)

October 3, 2018

Study Completion (Actual)

October 3, 2018

Study Registration Dates

First Submitted

May 17, 2016

First Submitted That Met QC Criteria

May 17, 2016

First Posted (Estimate)

May 18, 2016

Study Record Updates

Last Update Posted (Actual)

November 21, 2019

Last Update Submitted That Met QC Criteria

November 1, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1302.3
  • 2015-003718-25 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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