MTH1, A Phase I, Study on Tumors Inhibition, First in Human, First in Class

NCT03036228 | Completed Phase 1 DMC

• 1 other identifier: MASTIFF
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 3

Brief Summary

Primary Objective

• To determine the safety and tolerability of Karonudib (TH1579) in escalating doses for the treatment of patients with advanced solid malignant tumours. Secondary Objective
• To define DLT and MTD.
• To determine a recommended phase 2 dose (RP2D) and schedule.
• To determine the pharmacokinetics of Karonudib.
• To determine preliminary signs of clinical efficacy of Karonudib.
• To determine overall survival.

Conditions

Cancer

Keywords

Solid tumours

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of Karonudib (TH1579) will be evaluated.

  Dose Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD). DLTs will be assessed during first cycle of therapy, week 1-4 based on Haematological toxicity and Non-haematological toxicity. MTD: The highest dose of Karonudib that does not cause unacceptable side effects is defined as the MTD.

  28 days, first treatment cycle for the patient.

Secondary Outcomes (5)

• To determine the pharmacokinetics of Karonudib.

  28 days, first treatment cycle for the patient

• To determine the pharmacokinetics of Karonudib.

  28 days, first treatment cycle for the patient

• To determine the pharmacokinetics of Karonudib.

  28 days, first treatment cycle for the patient

• To determine the pharmacokinetics of Karonudib.

  28 days, first treatment cycle for the patient

• To determine preliminary signs of clinical efficacy of Karonudib.

  54 days, two treatment cycles for the patient

Study Arms (1)

Dose escalation

EXPERIMENTAL

Karonudib is an oral inhibitor of MTH1 supplied as an oral solution and now as tablets. Each cycle is defined as 28 days.

Drug: Karonudib

Interventions

Karonudib DRUG

Dose escalation of administration with Karonudib.

Dose escalation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent.
• Age at least 18 years (there is no upper age limit but patients must be judged to have a "biologic" age of 75 years or less).
• Life expectancy of at least 12 weeks (as per investigators clinical assessment).
• ECOG PFS 0 or 1.
• Patients must have measurable disease based on RECIST 1.1 criteria or evaluable metastatic disease unless otherwise specified in specific patient groups.
• Patients with any 1 of the following histologically confirmed tumors and who qualifies for new therapy and relapsing to/after standard therapy or the patient has refused or does not tolerate standard therapy Cohort 19
• Histologically or cytologically confirmed adenocarcinoma of prostate that is metastatic, hormone-refractory (confirmed by testing serum testosterone), and clinically progressive following at least one prior hormonal regimen. Prostate cancer patients must have measurable (patient with measurable bi-dimensional disease) or evaluable disease (defined as the presence of a non-measurable abnormality on CT or on physical examination coupled with an abnormal PSA value) or PSA relapse (Obtain sequence of rising values at a minimum of 1-week intervals, 1.0 ng/mL minimal value). Patients can only have received a taxane therapy in the pre-metastatic hormone refractory setting
• High Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer that can be assessed radiological, clinically or biochemically.
• Cytologically or histologically confirmed endometrial cancer that is recurrent or metastatic and/or resistant to standard therapies, or for which no standard therapy is available. Patients must have measurable disease based on RECIST 1.1 criteria or evaluable metastatic disease.
• Cohort 20
• Biopsy-proven carcinoma of the cervix that is either locally advanced or metastatic.
• Recurrent or metastatic head and neck adenocarcinoma who are not candidates for curative surgery or refusing surgical treatment
• Adequate bone marrow, hepatic and renal function defined as:
• Haemoglobin ≥ 95 g/L (blood transfusion not less than 21 days prior to screening).
• Absolute neutrophil count ≥ 1.5 x 109/L, platelets ≥100 x 109/L.

You may not qualify if:

• Age less than 18 years.
• Less than 4 weeks since stopping previous systemic cancer treatment or less than 5 half lifes of prior therapy, whichever is shorter.
• Less than 3 weeks since stopping palliative radiotherapy.
• Less than 3 weeks after minor surgery.
• Less than 6 months since a clinically significant cardiovascular event such as myocardial infarction, unstable angina, angioplasty, bypass surgery, stroke or TIA.
• Congestive heart failure NYHA class ≥ II.
• History of arrhythmias or arrhythmias discovered during the screening period (apart from atrial fibrillation without ventricular tachycardia and premature extra beats).
• Patients requiring anti-arrhythmic drugs.
• QTc interval \>450 ms at baseline.
• Use of fentanyl (must be stopped at least 1 week prior to initiation of Karonudib).
• Use of anti-oxidants vitamins and acetylcysteine (must be stopped within 48 hours of starting treatment with Karonudib).
• Use of antidepressant medications which are substrate for CYP2D6 (must be stopped at least 3 weeks prior to starting treatment with Karonudib).
• Any severe acute or chronic medical condition that places the patient at increased risk or interferes with the interpretation of study results.
• Known acute or chronic infection with hepatitis B or C that is untreated.
• Pregnant or breast-feeding women.

Sponsors & Collaborators

• Thomas Helleday Foundation: lead

Study Sites (3)

Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Karolinska University Hospital

Stockholm, Sweden

Location

Uppsala University Hospital

Uppsala, Sweden

Location

MeSH Terms

Conditions

Neoplasms

Interventions

karonudib

Study Officials

• Maria Klockare, BSc

  Oxcia

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: First part of the study - different dose cohorts with escalating doses. Extension part - Characterization of the Phase 2 Recommended Dose (P2RD) in specific patient groups and correlation with clinical outcome and other PD markers is currently examined.

Study Record Dates

• First Submitted: January 13, 2017
• First Posted: January 30, 2017
• Study Start: January 14, 2017
• Primary Completion: December 17, 2024
• Study Completion: December 17, 2024
• Last Updated: September 9, 2025

Record last verified: 2025-09

Locations

SE (3)