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NCT Number: NCT06853496

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

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.

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Key information

Conditions

Unresectable Colorectal Neoplasm Metastasis Colonic Diseases Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, 135-8550, Japan

Location status: Recruiting

Location contact

Eiji Shinozaki

CONTACT

[email protected]

+81-3-3520-0111

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

RK-582

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

Primary outcomes

  1. Percentage of dose-limiting toxicity

    Time frame: 35 days after the first dose of RK-582

  2. Number of participants with adverse events as assessed by CTCAE v5.0

    Time frame: Approximately 1 year after the first dose of RK-582

Secondary outcomes

  1. Area under the curve (AUC) after single or repeated dosing

    Time frame: 22 days after the first dose of RK-582

  2. Maximum plasma concentration (Cmax) after single or repeated dosing

    Time frame: 22 days after the first dose of RK-582

  3. Maximum concentration time (Tmax) after single or repeated dosing

    Time frame: 22 days after the first dose of RK-582

  4. Elimination rate constant (kel) after single or repeated dosing

    Time frame: 22 days after the first dose of RK-582

  5. Elimination half-life (t1/2) after single or repeated dosing

    Time frame: 22 days after the first dose of RK-582

  6. Apparent total body clearance (CLtot/F) after single or repeated dosing

    Time frame: 22 days after the first dose of RK-582

  7. Apparent volume of distribution (Vd/F) after single or repeated dosing

    Time frame: 22 days after the first dose of RK-582

  8. Objective response rate based on investigator's judgment as assessed by RECIST guideline ver. 1.1

    Time frame: Approximately 1 year after the first dose of RK-582

  9. Percentage of subjects who achieved a complete or partial response on the best overall response as assessed by RECIST guideline ver. 1.1

    Time frame: Approximately 1 year after the first dose of RK-582

  10. Duration of response as assessed by RECIST guideline ver. 1.1

    Time frame: Approximately 1 year after the first dose of RK-582

  11. Disease control rate as assessed by RECIST guideline ver. 1.1

    Time frame: Approximately 1 year after the first dose of RK-582

  12. Time to response as assessed by RECIST guideline ver. 1.1

    Time frame: Approximately 1 year after the first dose of RK-582

  13. Progression-free survival as assessed by RECIST guideline ver. 1.1

    Time frame: Approximately 1 year after the first dose of RK-582

  14. Overall survival

    Time frame: Approximately 30 months after the first dose of RK-582

Study contacts

Contact information is provided by the study sponsor or research team.

Eiji Shinozaki

CONTACT

[email protected]

+81-3-3520-0111

Sponsors and collaborators

Lead sponsor

Eiji Shinozaki

Other

Collaborators

  • Japan Agency for Medical Research and Development

Registry information

Official study title

Investigator-initiated Phase I Study of a Tankyrase Inhibitor RK-582 for Patients With Unresectable Metastatic Colorectal Cancer

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Mar 3, 2025
Registry last updated
Jul 29, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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