AzTrials
AzTrials

Colorectal CancerPhase 2DeFianCeNCT05480306

Phase 2 Study of DKN-01 in Colorectal Cancer

A Phase 2 study testing DKN-01, FOLFIRI and Bevacizumab in people with Colorectal Cancer and Colorectal Adenocarcinoma, run by Leap Therapeutics, Inc. at 40 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a Phase 2 randomized, open-label, two-part, multicenter study with a safety run-in to evaluate efficacy and safety of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus standard of care (SOC) [FOLFIRI/FOLFOX and bevacizumab] as second-line treatment of advanced CRC patients. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
DKN-01, FOLFIRI and Bevacizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
188 participants
Where
40 sitesin 3 countries
Study dates
30 Aug 2022to 10 Jul 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients meeting all of the following criteria will be considered eligible for study entry:
  • Disease progression following first-line systemic therapy with any fluoropyrimidine-based regimen for advanced disease (except FOLFOXIRI, see exclusion criteria).
  • Patients may have received prior neoadjuvant or adjuvant therapy which could have included irinotecan or oxaliplatin. If progression has occurred within 12 months from last dose of neoadjuvant or adjuvant treatment, this regimen will be considered as the one line of systemic therapy for advanced disease.
  • If assigned to receive FOLFIRI, patient may have received no prior irinotecan as part of first-line systemic therapy.
  • If assigned to receive FOLFOX, patient may have received no prior oxaliplatin as part of first line systemic therapy.
  • Prior treatment with an anti-VEGF or anti-EGFR therapy is allowed as first-line and/or maintenance systemic therapy.
Show all 11Show fewer
  • Able to provide written informed consent for any study specific procedures.
  • One or more tumors measurable on radiographic imaging as defined by RECIST 1.1
  • Sufficient tumor tissue for mandatory pre-treatment evaluation (fresh biopsy [preferred], or archived tissue block specimen).
  • ECOG performance status ≤1 within 7 days of first dose of study drug. Acceptable liver, renal, hematologic, and coagulation function
  • Females of childbearing potential and male partners of female patients must agree to use adequate contraception during the study and for 6 months after their last dose of study drug

Who cannot join

  • Patients meeting any of the following criteria are not eligible for study entry:
  • Diagnosis of Microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) and/or BRAF V600E mutation positive colorectal cancer.
  • Prior therapy with an anti-DKK1, FOLFOXIRI, PD-1, anti-PD-L1, anti-PD-L-2 or any other antibody or drug specifically targeting T-cell co-stimulation or coinhibitory checkpoint.
  • Systemic anti-cancer therapy within 28 days prior to first dose of study drug.
  • Major surgery within 28 days prior to first dose of study drug.
  • Prior radiation therapy within 14 days prior to first dose of study drug.
Show all 21Show fewer
  • Active leptomeningeal disease or uncontrolled brain metastases.
  • Any active cancer ≤ 2 years before first dose of study drug with the exception of cancer for this study.
  • New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia.
  • Fridericia-corrected QT interval (QTcF) > 470 msec (female) or history of congenital long QT syndrome.
  • Active, uncontrolled bacterial, viral, or fungal infections, within 14 days of study entry requiring systemic therapy.
  • Serious nonmalignant disease
  • Pregnant or nursing.
  • History of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on MRI scan that are symptomatic and clinically significant.
  • Known osteoblastic bony metastasis.
  • Major surgery 28 days prior to study entry.
  • Prior radiation therapy within 14 days prior to study entry.
  • Significant allergy to a pharmaceutical therapy that, in the opinion of the Investigator, poses an increased risk to the patient.
  • Active substance abuse.
  • Known dihydropyrimidine dehydrogenase deficiency.
  • Administration of a live vaccine within 28 days before first dose of study drug

Trial locations and contacts

40 sites in 3 countries.

40 sites in 3 countries

United States25 sites

  • Messino Cancer Centers

    Asheville, North Carolina, 28806

  • Hematology Oncology Clinic

    Baton Rouge, Louisiana, 70809

  • Center for Cancer and Blood Disorders

    Bethesda, Maryland, 20817

  • Florida Cancer Specialists & Research Institute (FCS)

    Cape Coral, Florida, 33909

  • Tennessee Oncology

    Chattanooga, Tennessee, 37404

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Florida Cancer Specialists & Research Institute

    Fleming Island, Florida, 32003

  • Florida Cancer Specialists & Research Institute

    Gainesville, Florida, 32605

  • Prisma Health Cancer Institute - Faris

    Greenville, South Carolina, 29605

  • Northwell Health

    Lake Success, New York, 11020

  • UCLA

    Los Angeles, California, 90404

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Miami Cancer Institute

    Miami, Florida, 33176

  • SCRI Oncology Partners

    Nashville, Tennessee, 37203

  • Tennessee Oncology

    Nashville, Tennessee, 37203

  • New York University

    New York, New York, 10016

  • Cornell University

    New York, New York, 10021

  • Mount Sinai Medical Center - New York

    New York, New York, 10029

  • Sanford Cancer Center

    Sioux Falls, South Dakota, 57104

  • Oncology Hematology Associates - Springfield

    Springfield, Missouri, 65807

  • MultiCare Tacoma General Hospital

    Tacoma, Washington, 98405

  • The University of Arizona Cancer Center

    Tucson, Arizona, 85719

  • Florida Cancer Specialists & Research Institute

    Wellington, Florida, 33414

  • White Plains Hospital

    White Plains, New York, 10601

  • Wake Forest University

    Winston-Salem, North Carolina, 27157

Other trials in United States

South Korea10 sites

  • Dong-A University Medical Center

    Busan

  • Kyungpook National University Chilgok Hospital

    Daegu

  • Gachon University Gil Medical Center

    Incheon

  • Inha University Hospital

    Incheon

  • CHA University - Bundang CHA General Hospital

    Seongnam-si

  • Seoul National University Bundang Hospital

    Seongnam-si

  • Asan Medical Center

    Seoul

  • Samsung Medical Center

    Seoul

  • Seoul National University Hospital

    Seoul

  • The Catholic University of Korea - St. Vincent's Hospital

    Suwon

Other trials in South Korea

Germany5 sites

  • Universitaetsklinikum Hamburg-Eppendorf (UKE) - Universitaeres Cancer Center Hamburg (UCCH)

    Hamburg

  • Universitaetsklinikum Heidelberg (UKHD) - Nationales Centrum fuer Tumorerkrankungen Heidelberg (NCT)

    Heidelberg

  • SLK-Kliniken Heilbronn GmbH - Klinikum am Gesundbrunnen - Klinik fuer Innere Medizin III

    Heilbronn

  • Gemeinschaftspraxis fuer Haematologie und Onkologie - Magdeburg

    Magdeburg

  • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz

    Mainz

Other trials in Germany

About this study

Official title: Randomized Phase 2 Study of DKN-01 Plus FOLFIRI/FOLFOX and Bevacizumab Versus FOLFIRI/FOLFOX and Bevacizumab as Second-line Treatment of Advanced Colorectal Cancer (DeFianCe)

This is a Phase 2 randomized, open-label, two-part, multicenter study with a safety run-in to evaluate efficacy and safety of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus standard of care (SOC) [FOLFIRI/FOLFOX and bevacizumab] as second-line treatment of advanced CRC patients.

Read the detailed description

This is a Phase 2 randomized, open-label, two-part, multicenter study with a safety run-in to evaluate efficacy and safety of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus standard of care (SOC) [FOLFIRI/FOLFOX and bevacizumab] as second-line treatment of advanced CRC patients.

In Parts A and B, approximately 200 evaluable adult advanced CRC patients with measurable disease (RECIST v1.1) who have radiographically progressed during or following 1 line of systemic treatment will be enrolled in the study.

The study consists of a Screening Period, a Treatment Period, a Safety Follow-up Period (SFUP) and a Long-Term Follow-up Period (LTFU). Patients will be followed in the SFUP for approximately 30 days (+7 days) after the last administration of study drug and then enter the LTFU period to be followed for survival and subsequent therapies. Additionally, patients that ended study treatment for a reason unrelated to progressive disease [PD] will also be followed for disease progression in the LTFU period.

Being tested
DKN-01, FOLFIRI, Bevacizumab, FOLFOX
Keywords
DKK1, colorectal cancer, DKN-01
Medical subject headings
Colorectal Neoplasms, Colonic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DKN-01Drug

    Also called LY2812176

    30 minute IV infusion (400mg) every two weeks with an additional loading dose in the first cycle of treatment

  • FOLFIRIDrug

    90-min IV infusion of irinotecan, leucovorin, and fluorouracil followed by a continuous 46-hour infusion of fluorouracil every two weeks

  • BevacizumabDrug

    90-min IV infusion (5mg)

  • FOLFOXDrug

    2 hour IV infusion of oxaliplatin, folinic acid, and fluorouracil followed by a continuous 46-hour infusion of fluorouracil every two weeks

Study groups in NCT05480306
Study groupRoleWhat they receive
TreatmentExperimentalDKN-01 + FOLFIRI or FOLFOX + bevacizumab
Receives: Drug: DKN-01; Drug: FOLFIRI; Drug: Bevacizumab; Drug: FOLFOX
ControlActive comparatorFOLFIRI or FOLFOX + bevacizumab
Receives: Drug: FOLFIRI; Drug: Bevacizumab; Drug: FOLFOX

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS)

    PFS, as determined by the Investigator per RECIST v1.1 of DKN-01 plus SOC versus SOC.

    Measured: approximately 6 months

Secondary outcomes (4)

  1. Objective Response Rate (ORR)

    ORR, as determined by the Investigator per RECIST v1.1 of DKN-01 plus SOC versus SOC

    Measured: approximately 6 months

  2. Duration of Response (DoR)

    DoR, as determined by the Investigator per RECIST v1.1 of DKN-01 plus SOC versus SOC

    Measured: approximately 6 months

  3. Overall Survival (OS)

    OS with DKN-01 plus SOC versus SOC

    Measured: approximately 6 months

  4. Incidence of ≥Grade 3 related treatment-related adverse events (TRAEs).

    Measured: approximately 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jul 2022
  2. Study start30 Aug 2022
  3. Primary completion10 Jul 2025
  4. Study completion10 Jul 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
188 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05480306
Sponsor's protocol ID
DEK-DKK1-P207
Acronym
DeFianCe
Status last verified
Jul 2025
First submitted
21 Jul 2022
Last updated
3 Aug 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DKN-01, FOLFIRI and Bevacizumab in people with Colorectal Cancer and Colorectal Adenocarcinoma, run by Leap Therapeutics, Inc. at 40 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in United States, South Korea, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: approximately 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05480306.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in