Advanced Solid TumorsPhase 1NCT02316197
Clinical Phase I Study Investigating MSC2490484A, an Inhibitor of a DNA-dependent Protein Kinase, in Advanced Solid Tumors or Chronic Lymphocytic Leukemia
A Phase 1 study testing MSC2490484A (M3814) in people with Advanced Solid Tumors and Chronic Lymphocytic Leukemia, run by Merck KGaA, Darmstadt, Germany at 7 sites in 3 countries.
Trial summary
MSC2490484A is an investigational drug that is being evaluated for the treatment of subjects with advanced solid tumors or chronic lymphocytic leukemia (CLL) that likely differs from other cancers in how it repairs damaged DNA (genetic material). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors, Chronic Lymphocytic Leukemia
- What is being tested?
- MSC2490484A (M3814)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 7 sitesin 3 countries
- Study dates
- 31 Dec 2014to 29 Jun 2017
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Advanced solid tumors likely to have alterations in DNA repair mechanisms, such as the BRCA and ATM pathways, or CLL, with no other standard surgical, radiation, or systemic anticancer therapies available. Subjects with CLL will be enrolled in 1 of the RP2D expansion cohorts only
- Tumor accessible for biopsies and agree to pretreatment tumor biopsy
- Measurable or evaluable disease in accordance with RECIST v 1.1 for solid tumors or Cheson´s criteria for CLL
- Male or female subjects at least 18 years of age who sign written informed consent.
- Other protocol-defined criteria could apply
Who cannot join
- Eastern Cooperative Oncology Group performance status > 1
- Prior treatment with chemotherapy, immunotherapy, hormonal therapy, with the exception of luteinizing hormone releasing hormone (LHRH) analogs, biologic therapy, any other anticancer therapy, or any other investigational agent within 28 days of the first dose of MSC2490484A (6 weeks for nitrosoureas or mitomycin C)
- Extensive prior radiotherapy on more than 30% of bone marrow reserves or prior bone marrow/stem cell transplantation within 5 years of study start. The extent of previous radiotherapy to the bone marrow will be determined by the investigator.
- Receiving medications or herbal supplements that are known to be potent inhibitors of cytochrome P450 3A4 or inducers of cytochrome P450 3A4.
- Not recovered from toxicity due to prior therapy to baseline or an AE CTCAE Grade of 1 or less (except alopecia)
- Poor vital organ function as defined in the protocol
Show all 9Show fewer
- Significant cardiac conduction abnormalities as defined in the protocol
- Central nervous system metastases unless previously radiotherapy treated, stable by computerized tomography (CT) scan for at least 3 months without evidence of cerebral edema, and no requirements for corticosteroids or anticonvulsants
- Other protocol-defined criteria could apply
Trial locations and contacts
7 sites in 3 countries.
7 sites in 3 countries
Netherlands3 sites
Antoni van Leeuwenhoek Ziekenhuis
Amsterdam
VU Medisch Centrum - Dept of Medical Oncology
Amsterdam
Erasmus Medisch Centrum - Parent
Rotterdam
Denmark2 sites
Rigshospitalet - Onkologisk KFE
Copenhagen
Herlev Hospital University of Copenhagen
Herlev
About this study
Official title: A Multicenter, Open-Label, Dose-Escalating Phase I Trial of the DNA-PK Inhibitor MSC2490484A in Subjects With Advanced Solid Tumors or Chronic Lymphocytic Leukemia
MSC2490484A is an investigational drug that is being evaluated for the treatment of subjects with advanced solid tumors or chronic lymphocytic leukemia (CLL) that likely differs from other cancers in how it repairs damaged DNA (genetic material). This is a first-in-man Phase I study, which means that it is the first time the study drug is being used in humans. The main purpose is to determine the highest dose that does not cause unacceptable side effects. The second is to determine the appropriate dose to use in future research for subjects with cancer. Othergoals of the study are to learn about the drug's safety and side effects, how it affects the tumor, and how the body processes the drug.
Read the detailed description
This is a Phase I, first-in-human, open-label, dose escalation, and dose expansion trial designed to explore the safety, tolerability, PK and PD profiles, and clinical activity of MSC2490484A administered daily as a single agent to subjects with advanced solid tumors or CLL likely to have alterations in DNA repair mechanisms.
Dose Escalation : Subjects will receive MSC2490484A continuously at the starting dose of 100 mg once daily. Sequential treatment cohorts will receive ascending doses of MSC2490484A once daily or twice daily (if determined to be appropriate by the Safety Monitoring Committee [SMC]) following a standard "3+3" design. The SMC will make dose escalation decisions based on review of available safety, tolerability, Pharmacokinetic (PK), and Pharmacodynamic (PD) data. Once the maximum tolerated dose (MTD) has been established, an Recommended Phase II Dose (RP2D) will be defined by the SMC, either at the MTD level or another dose level, depending on the available data on safety, efficacy, PK, and PD observed in the trial. The SMC may decide to stop dose escalation at any time during the trial.
Up to 12 subjects will be enrolled at the RP2D/Optimal biologic dose (OBD) to confirm safety and tolerability and explore the PK and PD profile of MSC2490484A.
Expansion cohorts: Once subjects have been evaluated at the RP2D, additional subjects will be enrolled into 2 or more expansion cohorts (20 evaluable subjects per expansion cohort) to evaluate clinical efficacy in tumors likely to have alterations in the DNA repair mechanism (eg, CLL and other tumor types). Subjects are evaluable for efficacy if they have received at least 1 dose of study drug and have radiographic baseline. Subjects who are not evaluable for efficacy will be replaced.
- Being tested
- MSC2490484A (M3814)
- Keywords
- DNA-PK Inhibitor, Advanced solid tumors, Chronic lymphocytic Leukemia, Phase I, first-in-human, Dose escalation, Dose expansion, Safety profile, Tolerability, PK, Antitumor activity, Maximum tolerated dose, M3814
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MSC2490484A (M3814)Drug
Also called M3814, Peposertib
Participants received MSC2490484A capsules at escalated dose from 100 mg to 400 mg orally from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814.
| Study group | Role | What they receive |
|---|---|---|
| MSC2490484A 100 mg QD | Experimental | Participants received MSC2490484A capsules 100 milligram (mg) orally, once daily (QD) from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814. Receives: Drug: MSC2490484A (M3814) |
| MSC2490484A 200 mg QD | Experimental | Participants received MSC2490484A capsules 200 mg orally, QD from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814. Receives: Drug: MSC2490484A (M3814) |
| MSC2490484A 150 mg BID | Experimental | Participants received MSC2490484A capsules 150 mg orally, twice daily (BID) from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814. Receives: Drug: MSC2490484A (M3814) |
| MSC2490484A 200 mg BID | Experimental | Participants received MSC2490484A capsules 200 mg orally, BID from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814. Receives: Drug: MSC2490484A (M3814) |
| MSC2490484A 300 mg BID | Experimental | Participants received MSC2490484A capsules 300 mg orally, BID from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814. Receives: Drug: MSC2490484A (M3814) |
| MSC2490484A 400 mg BID | Experimental | Participants received MSC2490484A capsules 400 mg orally, BID from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814. Receives: Drug: MSC2490484A (M3814) |
| MSC2490484A 400 mg BID RP2D | Experimental | Participants received MSC2490484A capsules 400 mg recommended Phase II dose (RP2D) orally, BID from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814. Receives: Drug: MSC2490484A (M3814) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Dose limiting toxicities (DLTs) occurring in Cycle 1
Measured: up to Day 21 of Cycle 1
Secondary outcomes (20)
Maximum Observed Plasma Concentration (Cmax)
Measured: Day 1 of Cycle 1 (cycle length = 21 days)
Time to Maximum Observed Plasma Concentration (tmax)
Measured: Day 1 of Cycle 1 (cycle length = 21 days)
Minimum Observed Plasma Concentration During a Complete Dosing Interval (Cmin)
Measured: Day 1 of Cycle 1 (cycle length = 21 days)
Average Observed Plasma Concentration (Cavg)
Measured: Day 1 of Cycle 1 (cycle length = 21 days)
Fluctuation Index
Measured: Day 1 of Cycle 1 (cycle length = 21 days)
Area Under the Concentration-Time Curve From Time Zero To 24 Hours (AUC0-24)
Measured: Day 1 of Cycle 1 (cycle length = 21 days)
Area Under the Concentration-Time Curve From Time Zero To 12 Hours (AUC0-12)
Measured: Day 1 of Cycle 1 (cycle length = 21 days)
Area Under the Concentration-Time Curve From Time Zero To the Time of Last Quantifiable Concentration (AUC0-t)
Measured: Day 1 of Cycle 1 (cycle length = 21 days)
Area Under the Concentration-Time Curve From Time Zero Extrapolated To Infinity (AUC0-inf)
Measured: Day 1 of Cycle 1 (cycle length = 21 days)
Area Under the Concentration-Time Curve From Time Zero to Time tau at Steady State (AUCtau)
Measured: Day 1 of Cycle 1 (cycle length = 21 days)
Apparent Terminal Half-Life (t1/2)
Measured: Day 1 of Cycle 1 (cycle length = 21 days)
Terminal Rate Constant (λz)
Measured: Day 1 of Cycle 1 (cycle length = 21 days)
Oral Clearance (CL/f)
Measured: Day 1 of Cycle 1 (cycle length = 21 days)
Apparent Volume of Distribution During Terminal Phase (Vz/f)
Measured: Day 1 of Cycle 1 (cycle length = 21 days)
Apparent Volume of Distribution at Steady State (Vss/f)
Measured: Day 1 of Cycle 1 (cycle length = 21 days)
Accumulation Ratio for Area Under The Concentration-Time Curve (Racc[AUC])
Measured: Day 1 of Cycle 1 (cycle length = 21 days)
Accumulation Ratio for Maximum Concentration (Racc[Cmax])
Measured: Day 1 of Cycle 1 (cycle length = 21 days)
Best overall response rate
Measured: Time from first dose to disease progression or death, whichever occurs first, assessed until 12 weeks after last patient treated
Clinical benefit rate defined as the proportion of subjects with CR, PR, or stable disease at Week 12
Measured: Week 12
Progression-free survival time (PFS)
Measured: Time from first dose to disease progression or death, whichever occurs first, assessed until 12 weeks after last patient treated
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2014 (estimated)
- Study start31 Dec 2014
- Primary completion29 Jun 2017
- Study completion29 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorsStudies 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
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02316197
- Sponsor's protocol ID
- EMR100036-001
- Other IDs
- 2014-003099-22, 2014
- Status last verified
- Apr 2020
- First submitted
- 10 Dec 2014
- Last updated
- 28 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
van Bussel MTJ, Awada A, de Jonge MJA, Mau-Sorensen M, Nielsen D, Schoffski P, Verheul HMW, Sarholz B, Berghoff K, El Bawab S, Kuipers M, Damstrup L, Diaz-Padilla I, Schellens JHM. A first-in-man phase 1 study of the DNA-dependent protein kinase inhibitor peposertib (formerly M3814) in patients with advanced solid tumours. Br J Cancer. 2021 Feb;124(4):728-735. doi: 10.1038/s41416-020-01151-6. Epub 2020 Nov 24.
PubMed 33230210
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-Label, Dose-Escalating Phase I Trial of the DNA-PK Inhibitor MSC2490484A in Subjects With Advanced Solid Tumors or Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT02316197
- Acronym / sponsor ID
- EMR100036-001
- Keywords
- DNA-PK Inhibitor, Advanced solid tumors, Chronic lymphocytic Leukemia, Phase I, first-in-human, Dose escalation, Dose expansion, Safety profile, Tolerability
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- 31 Dec 2014 (actual)
- Primary completion
- 29 Jun 2017 (actual)
- Study completion
- 29 Jun 2017 (actual)
- First posted
- 12 Dec 2014 (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.
MSC2490484A is an investigational drug that is being evaluated for the treatment of subjects with advanced solid tumors or chronic lymphocytic leukemia (CLL) that likely differs from other cancers in how it repairs damaged DNA (genetic material). This is a first-in-man Phase I study, which means that it is the first time the study drug is being used in humans. The main purpose is to determine the highest dose that does not cause unacceptable side effects. The second is to determine the appropriate dose to use in future research for subjects with cancer. Othergoals of the study are to learn about the drug's safety and side effects, how it affects the tumor, and how the body processes the drug.
Detailed description
This is a Phase I, first-in-human, open-label, dose escalation, and dose expansion trial designed to explore the safety, tolerability, PK and PD profiles, and clinical activity of MSC2490484A administered daily as a single agent to subjects with advanced solid tumors or CLL likely to have alterations in DNA repair mechanisms.
Dose Escalation : Subjects will receive MSC2490484A continuously at the starting dose of 100 mg once daily. Sequential treatment cohorts will receive ascending doses of MSC2490484A once daily or twice daily (if determined to be appropriate by the Safety Monitoring Committee [SMC]) following a standard "3+3" design. The SMC will make dose escalation decisions based on review of available safety, tolerability, Pharmacokinetic (PK), and Pharmacodynamic (PD) data. Once the maximum tolerated dose (MTD) has been established, an Recommended Phase II Dose (RP2D) will be defined by the SMC, either at the MTD level or another dose level, depending on the available data on safety, efficacy, PK, and PD observed in the trial. The SMC may decide to stop dose escalation at any time during the trial.
Up to 12 subjects will be enrolled at the RP2D/Optimal biologic dose (OBD) to confirm safety and tolerability and explore the PK and PD profile of MSC2490484A.
Expansion cohorts: Once subjects have been evaluated at the RP2D, additional subjects will be enrolled into 2 or more expansion cohorts (20 evaluable subjects per expansion cohort) to evaluate clinical efficacy in tumors likely to have alterations in the DNA repair mechanism (eg, CLL and other tumor types). Subjects are evaluable for efficacy if they have received at least 1 dose of study drug and have radiographic baseline. Subjects who are not evaluable for efficacy will be replaced.
Study design
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| MSC2490484A 100 mg QD | Experimental | Drug: MSC2490484A (M3814)Participants received MSC2490484A capsules 100 milligram (mg) orally, once daily (QD) from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814. |
| MSC2490484A 200 mg QD | Experimental | Drug: MSC2490484A (M3814)Participants received MSC2490484A capsules 200 mg orally, QD from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814. |
| MSC2490484A 150 mg BID | Experimental | Drug: MSC2490484A (M3814)Participants received MSC2490484A capsules 150 mg orally, twice daily (BID) from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814. |
| MSC2490484A 200 mg BID | Experimental | Drug: MSC2490484A (M3814)Participants received MSC2490484A capsules 200 mg orally, BID from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814. |
| MSC2490484A 300 mg BID | Experimental | Drug: MSC2490484A (M3814)Participants received MSC2490484A capsules 300 mg orally, BID from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814. |
| MSC2490484A 400 mg BID | Experimental | Drug: MSC2490484A (M3814)Participants received MSC2490484A capsules 400 mg orally, BID from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814. |
| MSC2490484A 400 mg BID RP2D | Experimental | Drug: MSC2490484A (M3814)Participants received MSC2490484A capsules 400 mg recommended Phase II dose (RP2D) orally, BID from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Advanced solid tumors likely to have alterations in DNA repair mechanisms, such as the BRCA and ATM pathways, or CLL, with no other standard surgical, radiation, or systemic anticancer therapies available. Subjects with CLL will be enrolled in 1 of the RP2D expansion cohorts only
- Tumor accessible for biopsies and agree to pretreatment tumor biopsy
- Measurable or evaluable disease in accordance with RECIST v 1.1 for solid tumors or Cheson´s criteria for CLL
- Male or female subjects at least 18 years of age who sign written informed consent.
- Other protocol-defined criteria could apply
Key exclusion criteria (9 listed)
- Eastern Cooperative Oncology Group performance status > 1
- Prior treatment with chemotherapy, immunotherapy, hormonal therapy, with the exception of luteinizing hormone releasing hormone (LHRH) analogs, biologic therapy, any other anticancer therapy, or any other investigational agent within 28 days of the first dose of MSC2490484A (6 weeks for nitrosoureas or mitomycin C)
- Extensive prior radiotherapy on more than 30% of bone marrow reserves or prior bone marrow/stem cell transplantation within 5 years of study start. The extent of previous radiotherapy to the bone marrow will be determined by the investigator.
- Receiving medications or herbal supplements that are known to be potent inhibitors of cytochrome P450 3A4 or inducers of cytochrome P450 3A4.
- Not recovered from toxicity due to prior therapy to baseline or an AE CTCAE Grade of 1 or less (except alopecia)
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 |
|---|---|---|
| MSC2490484A (M3814)Also: M3814, PeposertibParticipants received MSC2490484A capsules at escalated dose from 100 mg to 400 mg orally from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814. | Drug | MSC2490484A 100 mg QD, MSC2490484A 150 mg BID, MSC2490484A 200 mg BID, MSC2490484A 200 mg QD, MSC2490484A 300 mg BID, MSC2490484A 400 mg BID, MSC2490484A 400 mg BID RP2D |
Primary outcome
Number of Dose limiting toxicities (DLTs) occurring in Cycle 1
Time frame: up to Day 21 of Cycle 1
20 secondary outcomes
Maximum Observed Plasma Concentration (Cmax)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Time to Maximum Observed Plasma Concentration (tmax)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Minimum Observed Plasma Concentration During a Complete Dosing Interval (Cmin)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Average Observed Plasma Concentration (Cavg)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Fluctuation Index
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Area Under the Concentration-Time Curve From Time Zero To 24 Hours (AUC0-24)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Area Under the Concentration-Time Curve From Time Zero To 12 Hours (AUC0-12)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Area Under the Concentration-Time Curve From Time Zero To the Time of Last Quantifiable Concentration (AUC0-t)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Area Under the Concentration-Time Curve From Time Zero Extrapolated To Infinity (AUC0-inf)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Area Under the Concentration-Time Curve From Time Zero to Time tau at Steady State (AUCtau)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Apparent Terminal Half-Life (t1/2)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Terminal Rate Constant (λz)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Oral Clearance (CL/f)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Apparent Volume of Distribution During Terminal Phase (Vz/f)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Apparent Volume of Distribution at Steady State (Vss/f)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Accumulation Ratio for Area Under The Concentration-Time Curve (Racc[AUC])
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Accumulation Ratio for Maximum Concentration (Racc[Cmax])
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Best overall response rate
Time frame: Time from first dose to disease progression or death, whichever occurs first, assessed until 12 weeks after last patient treated
Clinical benefit rate defined as the proportion of subjects with CR, PR, or stable disease at Week 12
Time frame: Week 12
Progression-free survival time (PFS)
Time frame: Time from first dose to disease progression or death, whichever occurs first, assessed until 12 weeks after last patient treated
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 28 Apr 2020.
- Derived from this study: PubMed 33230210van Bussel MTJ, Awada A, de Jonge MJA, Mau-Sorensen M, Nielsen D, Schoffski P, Verheul HMW, Sarholz B, Berghoff K, El Bawab S, Kuipers M, Damstrup L, Diaz-Padilla I, Schellens JHM. A first-in-man phase 1 study of the DNA-dependent protein kinase inhibitor peposertib (formerly M3814) in patients with advanced solid tumours. Br J Cancer. 2021 Feb;124(4):728-735. doi: 10.1038/s41416-020-01151-6. Epub 2020 Nov 24.
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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.
Medical Responsible study director
Merck KGaA, Darmstadt, Germany
7 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MSC2490484A (M3814) in people with Advanced Solid Tumors and Chronic Lymphocytic Leukemia, run by Merck KGaA, Darmstadt, Germany at 7 sites in 3 countries.
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 5 inclusion and 9 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 28 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Netherlands, Belgium, Denmark. 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?
Number of Dose limiting toxicities (DLTs) occurring in Cycle 1 (time frame: up to Day 21 of Cycle 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02316197, which also lists 1 linked publication.
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 28 Apr 2020.