CancerPhase 1MASTIFFNCT03036228
MTH1, A Phase I, Study on Tumors Inhibition, First in Human, First in Class
A Phase 1 study testing Karonudib in people with Cancer, run by Thomas Helleday Foundation at 3 sites in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Cancer
- What is being tested?
- Karonudib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 3 sitesSweden
- Study dates
- 14 Jan 2017to 17 Dec 2024
- Phase
- Phase 1
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
- Total bilirubin < 1.5 x ULN (does not apply to patients with Gilberts Syndrome).
- AST and ALT ≤ 1.5 x ULN (or ≤ 3 x ULN in the presence of liver metastases).
- Serum creatinine not over ≤ ULN (if serum creatinine is between 1 and 1.5 x ULN, patients may be eligible provided that the calculated GFR is at least 50 ml/min using Cockcroft-Gault method).
- Albumin greater than or equal to 23 g/L.
- Subject must be able to take oral medication.
- Negative pregnancy test according to CTFG guidance 2014 for females of child-producing potential.
- Known HIV-infected patients with undetectable viral loads will be eligible for the study. HIV testing is mandatory
Who cannot join
- 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.
Show all 19Show fewer
- 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.
- Leptomeningeal metastases (patient with previously treated brain metastases are eligible provided that there is no evidence of disease progression for a minimum of 8 weeks prior to inclusion - in these cases a CNS MR is required within the screening period).
- Known acute or chronic infection with hepatitis B or C that is untreated.
- Pregnant or breast-feeding women.
- Patients with reproductive potential not implementing accepted and effective means of contraception.
- Participation in any other clinical trial within the previous 4 weeks.
- Unable to comply with study procedures.
Trial locations and contacts
3 sites in 1 country.
Sweden3 sites
Sahlgrenska University Hospital
Gothenburg
Karolinska University Hospital
Stockholm
Uppsala University Hospital
Uppsala
About this study
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
- Being tested
- Karonudib
- Keywords
- Solid tumours
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KaronudibDrug
Dose escalation of administration with Karonudib.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Karonudib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 days, first treatment cycle for the patient.
Secondary outcomes (5)
To determine the pharmacokinetics of Karonudib.
Peak Plasma Concentration, Cmax
Measured: 28 days, first treatment cycle for the patient
To determine the pharmacokinetics of Karonudib.
Tmax, time is the time to reach Cmax (Peak Plasma Concentration)
Measured: 28 days, first treatment cycle for the patient
To determine the pharmacokinetics of Karonudib.
biological half-life (plasma T1/2)
Measured: 28 days, first treatment cycle for the patient
To determine the pharmacokinetics of Karonudib.
Area under the Curve (AUC)
Measured: 28 days, first treatment cycle for the patient
To determine preliminary signs of clinical efficacy of Karonudib.
RECIST 1.1
Measured: 54 days, two treatment cycles for the patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2017 (estimated)
- Study start14 Jan 2017
- Primary completion17 Dec 2024
- Study completion17 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas Helleday Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Maria Klockare, BSc, Study director, Oxcia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03036228
- Sponsor's protocol ID
- MASTIFF
- Acronym
- MASTIFF
- Status last verified
- Sep 2025
- First submitted
- 13 Jan 2017
- Last updated
- 9 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MTH1, A Phase I, Study on Tumors Inhibition, First in Human, First in Class
- ClinicalTrials.gov ID
- NCT03036228
- Acronym / sponsor ID
- MASTIFF / MASTIFF
- Conditions
- Cancer
- Keywords
- Solid tumours
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- Thomas Helleday FoundationUniversity, hospital or other
- Study start
- 14 Jan 2017 (actual)
- Primary completion
- 17 Dec 2024 (actual)
- Study completion
- 17 Dec 2024 (actual)
- First posted
- 30 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Dose escalation | Experimental | Drug: KaronudibKaronudib is an oral inhibitor of MTH1 supplied as an oral solution and now as tablets. Each cycle is defined as 28 days. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KaronudibDose escalation of administration with Karonudib. | Drug | Dose escalation |
Primary outcome
Safety and tolerability of Karonudib (TH1579) will be evaluated.
Time frame: 28 days, first treatment cycle for the patient.
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.
5 secondary outcomes
To determine the pharmacokinetics of Karonudib.
Time frame: 28 days, first treatment cycle for the patient
To determine the pharmacokinetics of Karonudib.
Time frame: 28 days, first treatment cycle for the patient
To determine the pharmacokinetics of Karonudib.
Time frame: 28 days, first treatment cycle for the patient
To determine the pharmacokinetics of Karonudib.
Time frame: 28 days, first treatment cycle for the patient
To determine preliminary signs of clinical efficacy of Karonudib.
Time frame: 54 days, two treatment cycles for the patient
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maria Klockare, BSc study director
Oxcia
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Karonudib in people with Cancer, run by Thomas Helleday Foundation at 3 sites in Sweden.
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 22 inclusion and 19 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 9 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Sweden. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Safety and tolerability of Karonudib (TH1579) will be evaluated. (time frame: 28 days, first treatment cycle for the patient.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Sep 2025.