Study of a Tankyrase Inhibitor RK-582 for Patients With Unresectable Metastatic Colorectal Cancer

NCT ID: NCT06853496

Last Updated: 2025-07-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-13
• Study Completion Date: 2027-03-31

Brief Summary

Tankyrase, the fifth and sixth members of the poly(ADP-ribose) polymerase (PARP) family (PARP-5a/b), is responsible for poly(ADP-ribosyl)ation (PARylation), and was originally identified as a factor that promotes the function of telomerase, an enzyme that elongates telomeres. Subsequently, it was reported that tankyrase enhances Wnt/beta-catenin signaling by PARylation and subsequent degradation of AXIN, a negative regulator of Wnt/beta-catenin signaling, suggesting that tankyrase inhibitors may be a new treatment for colorectal cancer.

RK-582 was discovered through lead optimization from a tankyrase inhibitor that suppresses the growth of human colorectal cancer cells. It was confirmed that RK-582 selectively inhibited tankyrase among the PARP family enzymes, suppressed the growth of Wnt/beta-catenin signal-dependent human colorectal cancer cells at both the levels of cultured cells and xenograft tumors in immunodeficient mice, and accumulated AXIN to decrease beta-catenin and downregulate the target gene expression as pharmacodynamic biomarkers.

Based on these findings, RK-582 is thought to have potential as a new treatment for colorectal cancer patients. At present, however, the efficacy and safety of RK-582 in humans have not been confirmed. Thus, this clinical trial is conducted with the aim of investigating the tolerability and safety of RK-582 for patients with unresectable advanced or recurrent colorectal cancer as a first-in-human trial, in which RK-582 is administered to humans for the first time.

Conditions

Unresectable Colorectal Neoplasm Metastasis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RK-582

Group Type: EXPERIMENTAL

RK-582

Intervention Type: DRUG

Dosing Frequency:

Do single dose of RK-582 at the dose level specified for the cohort. Seven days after the first dose, Start repeated daily dose and continue until discontinuation criteria were met.

Dose level per dose:

Dose Level 1: 5 mg BID Dose level 2: 10 mg QD Dose level 3: 20 mg QD Dose level 4: 40 mg QD Dose Level 5: 60 mg QD Dose Level 6: 80 mg QD Dose Level 7: 100 mg QD Dose Level 8: 200 mg QD

Interventions

RK-582

Dosing Frequency:

Do single dose of RK-582 at the dose level specified for the cohort. Seven days after the first dose, Start repeated daily dose and continue until discontinuation criteria were met.

Dose level per dose:

Dose Level 1: 5 mg BID Dose level 2: 10 mg QD Dose level 3: 20 mg QD Dose level 4: 40 mg QD Dose Level 5: 60 mg QD Dose Level 6: 80 mg QD Dose Level 7: 100 mg QD Dose Level 8: 200 mg QD

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients with histologically or cytologically diagnosed colorectal cancer
• Patients who are refractory or intolerant to standard treatment for unresectable advanced or recurrent colorectal cancer
• Patients with measurable disease according to RECIST guideline ver 1.1
• Patients who are able to take capsules orally

Exclusion Criteria

• Patients with clinically relevant gastrointestinal, hepatic, musculoskeletal, respiratory, cerebral/cardiovascular, hematologic, oncologic, endocrine, immunologic, psychiatric, neurologic, or genitourinary diseases, or patients with conditions that are judged to threaten the safety of the participant or to affect the outcome of this clinical trial by the investigators
• Patients with medical history of interstitial lung disease
• Patients with chronic nausea, vomiting or diarrhea that may interfere with oral administration of the investigational drug
• Patients with pulmonary embolism or central deep vein thrombosis.
• Patients receiving treatment with strong CYP3A4 inhibitors or inducers.
• Patients diagnosed and treated for osteoporosis or patients with a bone mineral density of less than T-score -2.5 at the time of screening
• Patients with obvious bone metastases in the long bones, vertebrae, or other parts of the leg where gravity is applied

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Japan Agency for Medical Research and Development

OTHER_GOV

Sponsor Role: collaborator

Eiji Shinozaki

OTHER

Sponsor Role: lead

Responsible Party

Eiji Shinozaki

Vice Director of Gastroenterological Chemotherapy Department

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Kensei Yamaguchi

Role: STUDY_CHAIR

Cancer Institute Hospital of JFCR

Locations

Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, Japan

Site Status: RECRUITING

Countries

Japan

Central Contacts

Eiji Shinozaki

Role: CONTACT

eiji.shinozaki@jfcr.or.jp

+81-3-3520-0111

Facility Contacts

Eiji Shinozaki

Role: primary

eiji.shinozaki@jfcr.or.jp

+81-3-3520-0111

Other Identifiers

jRCT2031240702

Identifier Type: REGISTRY

Identifier Source: secondary_id

RK582CRCPI

Identifier Type: -

Identifier Source: org_study_id