What side effects are associated with this type of intervention?

Common treatments for colorectal cancer, such as FOLFIRI (folinic acid, fluorouracil, and irinotecan) and FOLFOX (folinic acid, fluorouracil, and oxaliplatin), often cause side effects including nausea, vomiting, diarrhea, mucositis, and myelosuppression (decreased bone marrow activity). Bevacizumab, an angiogenesis inhibitor used in combination with these regimens, can lead to hypertension, proteinuria, bleeding, and thromboembolic events. Additionally, chemotherapy-induced peripheral neuropathy is a notable side effect of oxaliplatin in the FOLFOX regimen.

What prior FDA approvals exist?

FDA-approved treatments for colorectal cancer include a variety of chemotherapeutic agents and targeted therapies. Commonly used chemotherapies include FOLFIRI (folinic acid, fluorouracil, and irinotecan) and FOLFOX (folinic acid, fluorouracil, and oxaliplatin). Targeted therapies such as bevacizumab (an anti-VEGF monoclonal antibody) and cetuximab (an anti-EGFR monoclonal antibody) are also approved. While specific FDA approvals for drugs targeting the Wnt signaling pathway in colorectal cancer are not detailed, ongoing research, such as the DKN-01 trial, aims to explore the efficacy of inhibiting the DKK1 protein in this pathway.

What other types of research exist?

Promising novel alternatives to DKN-01 for colorectal cancer patients in 2024 include therapies targeting the EGFR pathway (e.g., cetuximab, panitumumab), BRAF inhibitors (e.g., encorafenib combined with cetuximab), and immune checkpoint inhibitors (e.g., pembrolizumab for MSI-H/dMMR tumors). Additionally, therapies targeting the HER2 pathway (e.g., trastuzumab combined with pertuzumab) and novel agents in clinical trials such as bispecific antibodies and CAR-T cell therapies may offer new treatment options.

Monoclonal Antibodies

DKN-01 for Colorectal Cancer (DeFianCe Trial)

Nashville, TN

Phase 2

Waitlist Available

Research Sponsored by Leap Therapeutics, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up approximately 6 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new drug, DKN-01, combined with standard chemotherapy and bevacizumab for advanced colorectal cancer patients who didn't respond to earlier treatment. The treatment works by attacking cancer cells, blocking growth signals, and cutting off their blood supply.

See full description

Who is the study for?

Adults with advanced colorectal cancer (CRC) who've seen their disease progress after one line of systemic treatment. They must not have had certain prior treatments depending on the trial group they're assigned to, and should be in good physical condition (ECOG ≤1). Participants need measurable tumors and adequate organ function. Women of childbearing age and male partners must use contraception.

What is being tested?

The study is testing DKN-01 in combination with chemotherapy regimens FOLFIRI or FOLFOX plus bevacizumab against standard care for second-line treatment of CRC. It's a Phase 2 trial where patients are randomly chosen to receive either the test combo or the standard therapy.See study design

What are the potential side effects?

Potential side effects include those common to chemotherapy such as nausea, fatigue, hair loss, increased risk of infection, and blood clots. Bevacizumab can cause high blood pressure, bleeding problems, slow wound healing. Specific side effects from DKN-01 are not detailed but may align with typical immune therapy reactions.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ approximately 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~approximately 6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and approximately 6 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression Free Survival (PFS)

Secondary study objectives

Duration of Response (DoR)

Objective Response Rate (ORR)

Overall Survival (OS)

Other study objectives

Disease control rate (DCR)

Durable clinical benefit (DCB)

Duration of Complete Response (DoCR)

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: TreatmentExperimental Treatment4 Interventions

DKN-01 + FOLFIRI or FOLFOX + bevacizumab

Group II: ControlActive Control3 Interventions

FOLFIRI or FOLFOX + bevacizumab

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

DKN-01

2015

Completed Phase 1

~90

FOLFIRI

2005

Completed Phase 3

~5860

Bevacizumab

2013

Completed Phase 4

~5540

FOLFOX

2009

Completed Phase 3

~4560

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for colorectal cancer often target specific molecular pathways involved in tumor growth and progression. One such pathway is the Wnt signaling pathway, which is crucial for cell proliferation and differentiation. Inhibitors like DKN-01 target the DKK1 protein, an antagonist of Wnt signaling, to regulate intestinal epithelial homeostasis and potentially reduce tumor growth. Other treatments include targeting the RAS signaling pathway with farnesyl transferase inhibitors, especially in tumors with RAS mutations, and using EGFR inhibitors like cetuximab for tumors without RAS mutations. These targeted therapies are significant for colorectal cancer patients as they offer more personalized and potentially effective treatment options, minimizing damage to healthy cells and improving overall outcomes.