NCT02776683

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).

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
123

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Jun 2016

Geographic Reach
4 countries

46 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 17, 2016

Completed
1 day until next milestone

First Posted

Study publicly available on registry

May 18, 2016

Completed
21 days until next milestone

Study Start

First participant enrolled

June 8, 2016

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 3, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 3, 2018

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

November 21, 2019

Completed
Last Updated

November 21, 2019

Status Verified

October 1, 2019

Enrollment Period

2.3 years

First QC Date

May 17, 2016

Results QC Date

October 2, 2019

Last Update Submit

November 1, 2019

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (5)

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

    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

    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

    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

    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

    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).

Study Arms (1)

All patients

EXPERIMENTAL
Drug: BI 695502Drug: Avastin

Interventions

All patients
All patients

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (46)

Mayo Clinic-Arizona

Phoenix, Arizona, 85054, United States

Location

Pacific Cancer Medical Center, Inc.

Anaheim, California, 92801, United States

Location

The Oncology Institute of Hope and Innovation

Anaheim, California, 92801, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

Ashland Bellefonte Cancer Center

Ashland, Kentucky, 41101, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Aultman Hospital

Canton, Ohio, 44710, United States

Location

Oncology Hematology Care

Cincinnati, Ohio, 45242, United States

Location

Northwest Cancer Specialists PC

Portland, Oregon, 97225, United States

Location

Willamette Valley Cancer Institute and Research Center

Springfield, Oregon, 97477, United States

Location

Texas Oncology, P.A.

Abilene, Texas, 79606, United States

Location

Texas Oncology, PA,

Amarillo, Texas, 79106, United States

Location

Texas Oncology, P.A.

Austin, Texas, 78705, United States

Location

Texas Oncology, P.A.

Flower Mound, Texas, 75028, United States

Location

Texas Oncology, P.A.

Garland, Texas, 75042-5788, United States

Location

Oncology Consultants, P.A.

Houston, Texas, 77030, United States

Location

Texas Oncology, P.A.

McAllen, Texas, 78503-1298, United States

Location

Texas Oncology, PA

Mesquite, Texas, 75150, United States

Location

Texas Oncology-San Antonio Northeast

San Antonio, Texas, 78217, United States

Location

Texas Oncology San Antonio Medical Center

San Antonio, Texas, 78229, United States

Location

Tyler Hematology-Oncology, PA

Tyler, Texas, 75701, United States

Location

Texas Oncology, P.A.

Tyler, Texas, 75702, United States

Location

Texas Oncology, P.A., Deke Slayton Cancer Center

Webster, Texas, 77598, United States

Location

Virginia Cancer Institute

Richmond, Virginia, 23226, United States

Location

Chiba Cancer Center

Chiba, Chiba, 260-8717, Japan

Location

National Hospital Organization Shikoku Cancer Center

Ehime, Matsuyama, 791-0280, Japan

Location

Hokkaido University Hospital

Hokkaido, Sapporo, 060-8648, Japan

Location

Japan Organization of Occupational Health and Safety Kansai Rosai Hospital

Hyogo, Amagasaki, 660-8511, Japan

Location

Kagawa University Hospital

Kagawa, Kita-gun, 761-0793, Japan

Location

Osaka University Hospital

Osaka, Suita, 565-0871, Japan

Location

Jananese Foundation for Cancer Research

Tokyo, Koto-ku, 135-8550, Japan

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Duran i Reynals

L'Hospitalet de Llobregat, 08907, Spain

Location

Hospital ClĂ­nico de Valencia

Valencia, 46010, Spain

Location

CI Chernivtsi RC Oncological Dispensary Bukovinian SMU

Chernivtsi, 58013, Ukraine

Location

Munic.Instit."City Clin.Hosp.#4" of Dnipro City Council

Dnipropetrovsk, 49102, Ukraine

Location

Regional Clinical Oncological Dispensary, Ivano-Frankivsk

Ivano-Frankivsk, 76018, Ukraine

Location

CI of PH Kharkiv CCH #2

Kharkiv, 61037, Ukraine

Location

Treatment-Diagnostic CTR of Private Enterprise, Kirovohrad

Kirovohrad, 25006, Ukraine

Location

CI Kryvyi Rih Oncological Dispensary of DRC

Kryvyi Rih, Dnipropetrovsk, 50048, Ukraine

Location

National Institute of Cancer

Kyiv, 03022, Ukraine

Location

CI of LRC Lviv Onco.Reg.Treat.&Diag.Cent.

Lviv, 79031, Ukraine

Location

Poltava Regional Clinical Oncological Dispensary, Poltava

Poltava, 38011, Ukraine

Location

Sumy Regional Oncology Center

Sumy, 40022, Ukraine

Location

Vinnytsia Regional Clinical Oncological Dispensary

Vinnytsia, 21029, Ukraine

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Limitations and Caveats

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).

Results Point of Contact

Title
Boehringer Ingelheim, Call Centre
Organization
Boehringer Ingelheim

Study Officials

  • Boehringer Ingelheim

    Boehringer Ingelheim

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 17, 2016

First Posted

May 18, 2016

Study Start

June 8, 2016

Primary Completion

October 3, 2018

Study Completion

October 3, 2018

Last Updated

November 21, 2019

Results First Posted

November 21, 2019

Record last verified: 2019-10

Locations