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AzTrials

Advanced Solid TumorsPhase 1NCT02516813

Phase 1 Trial of MSC2490484A, an Inhibitor of a DNA-dependent Protein Kinase, in Combination With Radiotherapy

A Phase 1 study testing M3814 100 mg, M3814 200 mg and M3814 300 mg in people with Advanced Solid Tumors, run by EMD Serono Research & Development Institute, Inc. at 26 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

M3814 was an investigational drug that is being evaluated for the treatment of participants with locally advanced tumors. The main purposes of this study was to determine the safety, the tolerability and the efficacy of M3814 in combination with radiotherapy and in combination with chemoradiotherapy (Radiotherapy +… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumors
What is being tested?
M3814 100 mg, M3814 200 mg and M3814 300 mg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
26 sitesin 8 countries
Study dates
15 Sep 2015to 19 Nov 2021
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Phase Ia part: advanced solid tumors or metastases including lymphoma localized in the head and neck region or thorax with an indication for fractionated palliative RT (Arm A); or treatment-naïve SCCHN eligible for fractionated curatively intended RT with concurrent cisplatin (Arm B)
  • Phase Ib part: treatment-naïve Stage III A/B NSCLC not eligible for surgical resection or concurrent chemoradiation (Arm A expansion cohort) or treatment-naïve SCCHN eligible for fractionated curatively intended RT with concurrent cisplatin (Arm B expansion cohort)
  • Ancillary cPoP Part: any tumor with at least 2 (sub)cutaneous tumor/metastases at least 2 cm apart which are RT naïve with an indication for high dose palliative RT
  • Availability of archival tumor material, either as a block or slides (Phase Ia and Ib). If no archival material is available then a fresh biopsy should be taken
  • Willing to have tumor biopsies collected in Ancillary cPoP
  • Measurable or evaluable disease by RECIST v1.1 (not required for ancillary cPoP part of the study)
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  • Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1
  • Life expectancy of ≥ 3 months (Phase Ia, Arm A) or ≥ 6 months (Phase Ia, Arm B and Phase Ib)
  • Female subjects of childbearing potential and male subjects with female partners of childbearing potential must be willing to avoid pregnancy.

Who cannot join

  • Chemotherapy, immunotherapy, hormonal therapy, biologic therapy, or any other anticancer therapy or investigational medicinal product (IMP) within 28 days of first trial drug intake for Phase Ia subjects, and any prior therapy for Phase Ib subjects. For subjects with rapidly growing tumors localized in the head and neck region or thorax where the treating physician cannot wait for 28 days, inclusion may take place if there is no residual toxicity from previous treatment (maximum CTCAE Grade 1)
  • Prior RT to the same region within 12 months (Phase Ia, Arm A; subjects with tumors localized in the head and neck region or thorax) or at any time previously (Phase Ia, Arm B; treatment-naïve subjects with SCCHN and Phase Ib; treatment-naïve subjects with Stage III A/B NSCLC or SCCHN)
  • Extensive prior RT on ≥30% of bone marrow reserve as judged by the investigator or prior bone marrow/stem cell transplantation within 5 years before trial start.
  • Poor vital organ functions defined as:
  • Bone marrow impairment as evidenced by hemoglobin <10.0 g/dL, neutrophil count <1.0 × 109/L, platelets <100 × 109/L
  • Renal impairment as evidenced by serum creatinine >1.5 × upper limit of normal (ULN)
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  • Liver function abnormality as defined by total bilirubin >1.5 × ULN or aspartate aminotransferase (AST)/alanine aminotransferase (ALT) >2.5 × ULN (except for subjects with liver involvement, who can have AST/ALT >5 × ULN)
  • History of difficulty swallowing, malabsorption or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the IMP, use of percutaneous endoscopic gastrostomy (PEG) tubes
  • Significant cardiac conduction abnormalities, including a history of long QTc syndrome and/or pacemaker, or impaired cardiovascular function such as New York Heart Association classification score >2.
  • Subjects currently receiving (or unable to stop using prior to receiving the first dose of trial drug) medications or herbal supplements known to be potent inhibitors of cytochrome P450 (CYP)3A or CYP2C19 (must stop at least 1 week prior), potent inducers of CYP3A or CYP2C19 (must stop at least 3 weeks prior), or drugs mainly metabolized by CYP3A with a narrow therapeutic index (must stop at least one day prior).
  • Subjects currently receiving H2-blocker or proton pump inhibitors (or unable to stop at least 5 days prior to the first treatment).
  • If the planned radiation field includes any part of the esophagus and the subject has symptoms of ongoing esophagitis, the subject is not eligible, unless an esophageal endoscopy rules out the presence of esophagitis
  • Subjects where more than 10% of the total esophagus volume receives more than 50% of the prescribed RT dose
  • Main exclusion criteria for Ancillary Clinical Proof-of-Principle Part:
  • History of difficulty swallowing, malabsorption or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the IMP
  • History of any other significant medical disease such as major gastric or small bowel surgery, recent drainage of significant volumes of ascites or pleural effusion (as per Investigator's judgement) or a psychiatric condition that might impair the subject's well-being or preclude full participation in the trial
  • Subjects currently receiving (or unable to stop using prior to receiving the first dose of study drug) medications or herbal supplements known to be potent inhibitors of CYP3A or CYP2C19 must stop at least 1 week prior to taking MSC2490484A. Subjects receiving potent inducers of CYP3A or CYP2C19 must stop at least 3 weeks prior to taking MSC2490484A. Those receiving drugs mainly metabolized by CYP3A with a narrow therapeutic index as judged by the Investigator (and after optional consultation with the Sponsor) must stop at least one day prior to taking MSC2490484A.

Trial locations and contacts

26 sites in 8 countries.

26 sites in 8 countries

United States9 sites

  • Research site

    Billings, Montana, 59101

  • Holy Cross Hospital Inc.

    Fort Lauderdale, Florida, 33308

  • Research site

    Fresno, California, 93720

  • Research site

    Houston, Texas, 77030

  • University of Miami Miller School of Medicine

    Miami, Florida, 33136

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Research site

    Tacoma, Washington, 98405

  • Montefiore Medical Center PRIME

    The Bronx, New York, 10461

Other trials in United States

Germany9 sites

  • Charite Research Organisation GmbH - Phase - I Unit of Hematology and Oncology

    Berlin

  • Universitaetsklinikum Carl Gustav Carus TU Dresden

    Dresden

  • Universitaetsklinikum Essen - Westdeutsches Tumorzentrum

    Essen

  • Research site

    Freiburg im Breisgau, Baden-Wurttemberg, 79106

  • Universitaetsklinikum Heidelberg - RadioOnkologie und Strahlentherapie

    Heidelberg

  • Universitaetsklinikum Schleswig-Holstein - Campus Kiel - Klinik für diagnostische Radiologie

    Kiel

  • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz - Klinik und Poliklinik fuer Radiologie

    Mainz

  • Klinikum Mannheim GmbH Universitaetsklinikum - Parent

    Mannheim

  • Universitaetsklinikum Tuebingen - Medizinische Klinik I

    Tübingen

Other trials in Germany

Denmark2 sites

  • Rigshospitalet - PARENT

    Copenhagen

  • Herlev Hospital - PARENT

    Herlev

Other trials in Denmark

Netherlands2 sites

  • Research site

    Amsterdam, 1066 CX

  • Antoni van Leeuwenhoek Ziekenhuis

    Amsterdam

Other trials in Netherlands

Belgium1 site

  • Research site

    Leuven

Other trials in Belgium

Norway1 site

  • Research site

    Oslo

Other trials in Norway

Sweden1 site

  • Karolinska universitetssjukhuset - Solna - Radiumhemmet (onkologi)

    Solna

Other trials in Sweden

Switzerland1 site

  • Universitaetsspital Zuerich - Parent

    Zurich

Other trials in Switzerland

About this study

Official title: An Open Label, Phase Ia/Ib Trial of the DNA-PK Inhibitor MSC2490484A in Combination With Radiotherapy in Patients With Advanced Solid Tumors

M3814 was an investigational drug that is being evaluated for the treatment of participants with locally advanced tumors. The main purposes of this study was to determine the safety, the tolerability and the efficacy of M3814 in combination with radiotherapy and in combination with chemoradiotherapy (Radiotherapy + cisplatin).

Being tested
M3814 100 mg, M3814 200 mg, M3814 300 mg, M3814 400 mg, M3814 50 mg
Keywords
M3814, Advanced solid tumors, DNA-PK Inhibitor, Radiotherapy, Chemotherapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • M3814 100 mgDrug

    Also called Peposertib, MSC2490484A

    Participants received 100 mg of M3814 as capsule or tablet orally once daily.

  • M3814 200 mgDrug

    Also called Peposertib, MSC2490484

    Participants received 200 mg of M3814 as capsule or tablet orally once daily.

  • M3814 300 mgDrug

    Also called Peposertib, MSC2490484

    Participants received 300 mg of M3814 as capsule or tablet orally once daily.

  • M3814 400 mgDrug

    Also called Peposertib, MSC2490484

    Participants received 400 mg of M3814 as capsule or tablet orally once daily.

  • M3814 50 mgDrug

    Also called Peposertib, MSC2490484

    Participants received 100 mg of M3814 as capsule orally once daily.

  • Fractionated RTRadiation

    Participants received fractionated palliative RT (3 Gray [Gy] * 10 in Arm A and 2 Gy * 33 to 35, 5 fractions per week [F/W]) in Arm B and received a single high dose of RT (10-25 Gy) capsule on Day 1 given on Lesion 1 and a single high dose of RT (10-25 Gy) on Day 2 given on Lesion 2 in ancillary CPoP part.

  • CisplatinDrug

    Participants received Cisplatin twice at a dose of 100 mg/m^2 or weekly at a dose of 40 mg/m^2.

Study groups in NCT02516813
Study groupRoleWhat they receive
Phase 1a (Arm A): M3814 Capsule (100 mg) + RTExperimentalParticipants with locally advanced disease (any tumor or metastases including lymphomas) localized in the head and neck region or thorax that was not amenable to surgical therapy, or with standard systemic therapy with an indication for palliative radiotherapy (RT) received 100 milligrams (mg) of M3814 as capsule orally once daily on fraction day (FD) 6 in combination with RT (3 Gray [Gy] x 10, 5 fractions per week [F/W]).
Receives: Drug: M3814 100 mg; Radiation: Fractionated RT
Phase 1a (Arm A): M3814 Capsule (200 mg) + RTExperimentalParticipants with locally advanced disease (any tumor or metastases including lymphomas) localized in the head and neck region or thorax that was not amenable to surgical therapy, or with standard systemic therapy with an indication for palliative RT received 200 mg of M3814 as capsule orally once daily on FD 6 in combination with RT (3 [Gy] x 10, 5 F/W).
Receives: Drug: M3814 200 mg; Radiation: Fractionated RT
Phase 1a (Arm A): M3814 Capsule (300 mg) + RTExperimentalParticipants with locally advanced disease (any tumor or metastases including lymphomas) localized in the head and neck region or thorax that was not amenable to surgical therapy, or with standard systemic therapy with an indication for palliative RT received 300 mg of M3814 as capsule orally once daily on FD 6 in combination with RT (3 [Gy] x 10, 5 F/W).
Receives: Drug: M3814 300 mg; Radiation: Fractionated RT
Phase 1a (Arm A): M3814 Capsule (400 mg) + RTExperimentalParticipants with locally advanced disease (any tumor or metastases including lymphomas) localized in the head and neck region or thorax that was not amenable to surgical therapy, or with standard systemic therapy with an indication for palliative RT received 400 mg of M3814 as capsule orally once daily on FD 6 in combination with RT (3 [Gy] x 10, 5 F/W).
Receives: Drug: M3814 400 mg; Radiation: Fractionated RT
Phase 1a (Arm A): M3814 Tablet (100 mg) + RTExperimentalParticipants with locally advanced disease (any tumor or metastases including lymphomas) localized in the head and neck region or thorax that was not amenable to surgical therapy, or with standard systemic therapy with an indication for palliative RT received 100 mg of M3814 as tablet orally once daily for 2 consecutive weeks in combination with RT (3 Gy x 10, 5 F/W).
Receives: Drug: M3814 100 mg; Radiation: Fractionated RT
Phase 1a (Arm A): M3814 Tablet (200 mg) + RTExperimentalParticipants with locally advanced disease (any tumor or metastases including lymphomas) localized in the head and neck region or thorax that was not amenable to surgical therapy, or with standard systemic therapy with an indication for palliative RT received 200 mg of M3814 as tablet orally once daily for 2 consecutive weeks in combination with RT (3 Gy x 10, 5 F/W).
Receives: Drug: M3814 200 mg; Radiation: Fractionated RT
Phase 1a (Arm A): M3814 Tablet (300 mg) + RTExperimentalParticipants with locally advanced disease (any tumor or metastases including lymphomas) localized in the head and neck region or thorax that was not amenable to surgical therapy, or with standard systemic therapy with an indication for palliative RT received 300 mg of M3814 as tablet orally once daily for 2 consecutive weeks in combination with RT (3 Gy x 10, 5 F/W).
Receives: Drug: M3814 300 mg; Radiation: Fractionated RT
Phase 1a (Arm B): M3814 Capsule (50 mg) + CRTExperimentalParticipants with local/locally advanced squamous cell carcinoma of the head and neck (SCCHN) received 50 mg of M3814 as capsule orally once daily on FD 6 in combination with fractionated RT (2 Gy x 33 to 35 fractions; 5 F/W) and Cisplatin twice at a dose of 100 milligrams per square meter (mg/m^2) or weekly at a dose of 40 (mg/m^2).
Receives: Drug: M3814 50 mg; Radiation: Fractionated RT; Drug: Cisplatin
Phase 1a (Arm B): M3814 Tablet (100 mg) + CRTExperimentalParticipants with squamous cell carcinoma of the head and neck (SCCHN) received 100 mg of M3814 as tablet orally once daily for 7 consecutive weeks in combination with fractionated RT (2 Gy X 33 to 35 fractions; 5 F/W) and Cisplatin twice at a dose of 100 mg/m^2 or weekly at a dose of 40 (mg/m^2).
Receives: Radiation: Fractionated RT; Drug: Cisplatin
Ancillary cPoP: M3814 Capsule (100 mg) + RTExperimentalParticipants with at least 2 (sub)cutaneous tumor/metastases of any type (at least 2 centimeters [cm] apart) with an indication for single high dose-palliative RT were included and received single oral dose of M3814 capsule at a dose of 100 mg on Day 2, prior 1.5 hours start of RT and a single high dose of RT (10-25 Gy) on Lesion 1 on Day 1 and on Lesion 2 on Day 2.
Receives: Drug: M3814 100 mg; Radiation: Fractionated RT
Ancillary cPOP: M3814 Capsule (200 mg) + RTExperimentalParticipants with at least 2 (sub)cutaneous tumor/metastases of any type (at least 2 cm apart) with an indication for single high dose-palliative RT were included and received single oral dose of M3814 capsule at a dose of 200 mg on Day 2, prior 1.5 hours start of RT and a single high dose of RT (10-25 Gy) on Lesion 1 on Day 1 and on Lesion 2 on Day 2.
Receives: Drug: M3814 200 mg; Radiation: Fractionated RT
Ancillary cPOP: M3814 Capsule (400 mg) + RTExperimentalParticipants with at least 2 (sub)cutaneous tumor/metastases of any type (at least 2 cm apart) with an indication for single high dose-palliative RT were included and received single oral dose of M3814 capsule at a dose of 400 mg on Day 2, prior 1.5 hours start of RT and a single high dose of RT (10-25 Gy) on Lesion 1 on Day 1 and on Lesion 2 on Day 2
Receives: Drug: M3814 400 mg; Radiation: Fractionated RT

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1a (Arm A): Number of Participants Who Experienced at Least One Dose-limiting Toxicity (DLT) According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)

    DLT: any Grade (Gr) greater than or equal to (>=) 3 nonhematologic adverse event (AE)/any Gr>=4 hematologic AE that is related to any of study treatments and occurs during the DLT period of 5 weeks (Phase Ia, Arm A) after the first dose of M3814. Following are considered as DLTs: Gr3 thrombocytopenia with medically concerning bleeding; Febrile neutropenia; Any toxicity/study treatment-related adverse event (TEAE) that, in opinion of Safety Monitoring Committee (SMC), is of potential clinical significance such that further dose escalation would expose participants to unacceptable risk; Any toxicity related to study treatments that causes participant to receive less than 80 percent (%) of the planned RT dose; Evidence of study treatment-related hepatocellular injury for > 3 days.

    Measured: Time from first dose of study treatment up to 5 weeks

  2. Phase 1a (Arm B): Number of Participants Who Experienced at Least One Dose-limiting Toxicity (DLT) According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)

    DLT: any Grade (Gr) greater than or equal to (>=) 3 nonhematologic AE/any Gr>=4 hematologic AE that is related to any of study treatments and occurs during the DLT period of 12 weeks (Phase Ia, Arm B) after the first dose of M3814. Following are considered as DLTs: Gr3 thrombocytopenia with medically concerning bleeding; Febrile neutropenia; Any toxicity/study treatment-related adverse event (TEAE) that, in opinion of Safety Monitoring Committee (SMC), is of potential clinical significance such that further dose escalation would expose participants to unacceptable risk; Any toxicity related to study treatments that causes participant to receive less than 80 percent (%) of the planned RT dose; Any toxicity related to study treatments leading to an interruption of RT longer than 1 week in Arm B; Evidence of study treatment-related hepatocellular injury for > 3 days.

    Measured: Time from first dose of study treatment up to 12 weeks

Secondary outcomes (31)

  1. Phase 1a (Arm A and Arm B): Number of Participants With Grade Greater Than or Equal to (>=) 3 Treatment-Emergent Adverse Events (TEAEs) According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)

    Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily have a causal relationship with this treatment. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: TEAEs was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious AEs and non-serious AEs. As per NCI-CTCAE v4.03, Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death. Number of participants with Grade >=3 TEAEs were reported.

    Measured: Time from first dose of study treatment up to long term safety follow-up period (Up to approximately 1 year)

  2. Phase 1a (Arm A and Arm B): Number of Participants With Shifts From Baseline to Worst Post-Baseline Grade in Hematology Parameters According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTC v4.03)

    Number of participants with shifts from Baseline values (Grade 0/1/2) to worst post-baseline values (Grade 1/2/3/4) were reported as per NCI-CTCAE, v4.03 graded from Grade 1 to 5. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death. Shifts in hematology parameter (hemoglobin low, leukocytes low, lymphocytes low, neutrophil count decreased, and platelet count decreased) were reported.

    Measured: Time from first dose of study treatment up to long term safety follow-up period (Up to approximately 1 year)

  3. Phase 1a (Arm A and Arm B): Number of Participants With Shifts From Baseline to Worst Post-Baseline Grade in Biochemistry Parameters According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)

    Number of participants with shifts from Baseline values (Grade 0/1/2) to worst post-baseline values (Grade 1/2/3/4) were reported as per NCI-CTCAE, v4.03 graded from Grade 1 to 5. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death. Shifts in biochemistry parameter (phosphate low, potassium low, sodium low, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, blood bilirubin increased, glucose high, glucose low, albumin low and creatinine increased) were reported.

    Measured: Time from first dose of study treatment up to long term safety follow-up period (Up to approximately 1 year)

  4. Phase 1a (Arm A and Arm B): Number of Participants With Markedly Abnormal Vital Sign Measurements

    Vital sign assessments included assessments of heart rate, blood pressure, body weight and body temperature. Abnormal vital sign measurement was decided by Investigator. Number of participants with markedly abnormal vital sign measurements were reported.

    Measured: Time from first dose of study treatment up to long term safety follow-up period (Up to approximately 1 year)

  5. Phase 1a (Arm A and Arm B): Number of Participants With Shifts From Normal Baseline to Abnormal Post-baseline in Electrocardiogram (ECG)

    Electrocardiograms (ECG) was obtained after the participant has been in a supine position for at least 5 minutes. ECG parameters included heart rate, atrial ventricular conduction, QR and QT intervals (including QTcF), and possible arrhythmias. Any ECG finding that was judged by the investigator as a abnormal (worsening) compared with a baseline value was considered an adverse event. Number of participants with shifts from normal baseline values to abnormal post-baseline values in ECG were reported.

    Measured: Time from first dose of study treatment up to long term safety follow-up period (Up to approximately 1 year)

  6. Phase 1a (Arm A and Arm B): Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator

    Confirmed BOR was defined as best response of any of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from date of randomization until disease progression. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD: defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. CR or PR must be confirmed by a subsequent tumor assessment, at least 4 weeks after initial documentation of CR or PR.

    Measured: Time from first dose of study treatment up to long term safety follow-up period (Up to approximately 1 year)

  7. Phase 1a (Arm A and Arm B): Number of Participants With Unconfirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator

    Unconfirmed BOR was defined as unconfirmed best response of any of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from date of randomization until disease progression. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD: defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

    Measured: Time from first dose of study treatment up to long term safety follow-up period (Up to approximately 1 year)

  8. Phase 1a (Arm A and Arm B): Median Percent Change From Baseline in Tumor Size Measurement According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator

    The tumor size was defined as the sum of the longest diameters for the target lesions. The sum of lesion diameters was calculated using RECIST v1.1 and was assessed by Investigator.

    Measured: Time from first dose of study treatment up to long term safety follow-up period (Up to approximately 1 year)

  9. Phase 1a (Arm A and Arm B): Maximum Plasma Concentration (Cmax) of M3814 After Single Dose

    Cmax was taken directly from the observed concentration-time curve.

    Measured: Pre-dose, 0.5, 1, 2, 4, 6 hours post-dose on Fraction Day 1 and Fraction Day 6

  10. Phase 1a (Arm A and Arm B): Time to Reach Maximum Plasma Concentration (Tmax) of M3814 After Single Dose

    tmax was obtained directly from the concentration versus time curve.

    Measured: Pre-dose, 0.5, 1, 2, 4, 6 hours post-dose on Fraction Day 1 and Fraction Day 6

  11. Phase 1a (Arm A and Arm B): Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M3814 After Single Dose

    AUC0-24 of M3814 was defined as the area under the concentration time curve from time 0 to 24 hours post-dose.

    Measured: Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Fraction Day 1 and Fraction Day 6

  12. Phase 1a (Arm A and Arm B): Area Under the Plasma Concentration-Time From Time Zero Extrapolated to Infinity (AUC0-inf) of M3814 After Single Dose

    The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from the determination of the terminal first order (elimination) rate constant (lambda z). AUC0-inf = AUC0-t plus Clast pred/lambda z. Lambda z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.

    Measured: Pre-dose, 0.5, 1, 2, 4, 6 hours post-dose on Fraction Day 1 and Fraction Day 6

  13. Phase 1a (Arm A and Arm B): Apparent Terminal Half Life (t1/2) of M3814 After Single Dose

    t1/2 was the time measured for the concentration to decrease by one half. t1/2 was calculated by natural log 2 divided by Lambda z.

    Measured: Pre-dose, 0.5, 1, 2, 4, 6 hours post-dose on Fraction Day 1 and Fraction Day 6

  14. Phase 1a (Arm A and Arm B): Total Body Clearance Following Oral Administration (CL/f) of M3814 After Single Dose

    The apparent total body clearance of study intervention following extravascular administration on FD1, taking into account the fraction of dose absorbed. CL/f = Dose oral (p.o.)/AUC0-inf. The predicted AUC0-inf should be used.

    Measured: Pre-dose, 0.5, 1, 2, 4, 6 hours post-dose on Fraction Day 1 and Fraction Day 6

  15. Phase 1a (Arm A and Arm B): Apparent Volume of Distribution (Vz/f) of M3814 After Single Dose

    Apparent volume of distribution during the terminal phase following extravascular administration for M8891 was calculated. Vz/f = Dose/(AUC0-infinity multiply by Lambda z) following single dose. The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda z determination. AUC(0- inf)=AUC0-t plus Clastpred/lambda z where Clastpred was last predicted concentration. Lambda Z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.

    Measured: Pre-dose, 0.5, 1, 2, 4, 6 hours post-dose on Fraction Day 1 and Fraction Day 6

  16. Phase 1a (Arm A and Arm B): Maximum Plasma Concentration (Cmax) of M3814 After Multiple Dose

    Cmax was taken directly from the observed concentration-time curve.

    Measured: Pre-dose, 0.5, 1, 2 and 4 hours post-dose on Fraction Day 10

  17. Phase 1a (Arm A and Arm B): Time to Reach Maximum Plasma Concentration (Tmax) of M3814 After Multiple Dose

    tmax was obtained directly from the concentration versus time curve.

    Measured: Pre-dose, 0.5, 1, 2 and 4 hours post-dose on Fraction Day 10

  18. Phase 1a (Arm A and Arm B): Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUCtau) of M3814 After Multiple Dosing

    AUCtau was defined as area under the plasma concentration-time curve from time zero to the end of the dosing interval (tau). AUCtau was calculated using the mixed log linear trapezoidal rule.

    Measured: Pre-dose, 0.5, 1, 2 and 4 hours post-dose on Fraction Day 10

  19. Phase 1a (Arm A and Arm B): Area Under the Plasma Concentration-Time From Time Zero Extrapolated to Infinity (AUC0-inf) of M3814 After Multiple Dose

    The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from the determination of the terminal first order (elimination) rate constant (lambda z). AUC0-inf = AUC0-t plus Clast pred/lambda z. Lambda z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.

    Measured: Pre-dose, 0.5, 1, 2 and 4 hours post-dose on Fraction Day 10

  20. Phase 1a (Arm A and Arm B): Apparent Terminal Half Life (t1/2) of M3814 After Multiple Dose

    t1/2 was the time measured for the concentration to decrease by one half. t1/2 was calculated by natural log 2 divided by Lambda z.

    Measured: Pre-dose, 0.5, 1, 2 and 4 hours post-dose on Fraction Day 10

  21. Phase 1a (Arm A and Arm B): Oral Clearance in Plasma at Steady State (CLss/f) of M3814 After Multiple Dose

    Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

    Measured: Pre-dose, 0.5, 1, 2 and 4 hours post-dose on Fraction Day 10

  22. Phase 1a (Arm A and Arm B): Apparent Volume of Distribution at Steady-State (Vss/f) of M3814 After Multiple Dose

    Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss/f after oral dose was influenced by the fraction absorbed.

    Measured: Pre-dose, 0.5, 1, 2 and 4 hours post-dose on Fraction Day 10

  23. Phase 1a (Arm A and Arm B): Accumulation Ratio of Area Under the Concentration-Time Curve (AUC) [Racc(AUC0-24)] of M3814 After Multiple Dose

    Accumulation ratio for AUC was calculated as AUC, after dosing on fraction Day 10 divided by AUC, after dosing on fraction Day 1 of cycle 1.

    Measured: Pre-dose, 0.5, 1, 2, 4 and 24 hours post-dose on Fraction Day 1 and Fraction Day 10

  24. Phase 1a (Arm A and Arm B): Accumulation Ratio of Cmax (Racc (Cmax) of M3814 After Multiple Dose

    Accumulation ratio for Cmax was calculated as Cmax, after dosing on fraction Day 10 divided by Cmax, after dosing on fraction Day 1 of cycle 1.

    Measured: Pre-dose, 0.5, 1, 2 and 4 hours post-dose on Fraction Day 1 and Fraction Day 10

  25. Ancillary cPoP: Maximum Observed Plasma Concentration (Cmax) of M3814

    Cmax was taken directly from the observed concentration-time curve.

    Measured: Pre-dose, 0.5, 1, 2, 4, 6 hours post-dose on Fraction Day 2

  26. Ancillary cPoP: Time to Reach Maximum Plasma Concentration (Tmax) of M3814

    tmax was obtained directly from the concentration versus time curve.

    Measured: Pre-dose, 0.5, 1, 2, 4, 6 hours post-dose on Fraction Day 2

  27. Ancillary cPoP: Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours (AUC0-4) of M3814

    AUC0-4hr is the area under the plasma concentration-time curve from time 0 to 4 hours post-dose. This is a measure of the average amount of study drug M3814 in the blood plasma over a period of 4 hours after the dose.

    Measured: Pre-dose, 0.5, 1, 2 and 4 hours post-dose on Fraction Day 2

  28. Ancillary cPoP: Area Under the Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) (AUC0-t) of M3814

    Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.

    Measured: Pre-dose, 0.5, 1, 2, 4, 6 hours post-dose on Fraction Day 2

  29. Ancillary cPoP: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of M3814

    AUC0-t/Dose was defined as AUC from time of dosing to the time of the last measurable concentration divided by dose.

    Measured: Pre-dose, 0.5, 1, 2, 4, 6 hours post-dose on Fraction Day 2

  30. Ancillary cPoP: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to 4 Hours (AUC0-4)/Dose of M3814

    AUC0-4/Dose was defined as AUC from time of dosing to the time zero to 4 hours divided by dose.

    Measured: Pre-dose, 0.5, 1, 2 and 4 hours post-dose on Fraction Day 2

  31. Ancillary cPoP: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M3814

    Cmax/Dose was calculated as maximum observed plasma concentration obtained directly from the concentration versus time curve divided by dose. Cmax/dose was measured in nanogram per milliliter per milligram (ng/mL/mg).

    Measured: Pre-dose, 0.5, 1, 2, 4, 6 hours post-dose on Fraction Day 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Aug 2015 (estimated)
  2. Study start15 Sep 2015
  3. Primary completion26 Mar 2021
  4. Study completion19 Nov 2021

Resources

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02516813
Sponsor's protocol ID
100036-002
Other IDs
2015-000673-12, 2015
Status last verified
Jul 2024
First submitted
4 Aug 2015
Last updated
15 Oct 2024
Data monitoring committee
Yes
Individual data sharing
No: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing M3814 100 mg, M3814 200 mg and M3814 300 mg in people with Advanced Solid Tumors, run by EMD Serono Research & Development Institute, Inc. at 26 sites in 8 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 9 inclusion and 17 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 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States, Germany, Denmark, Netherlands, Belgium and 3 more countries. 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?

Yes. Results are posted in the registry (first posted 15 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Phase 1a (Arm A): Number of Participants Who Experienced at Least One Dose-limiting Toxicity (DLT) According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) (time frame: Time from first dose of study treatment up to 5 weeks). The study lists 2 primary outcomes in all. 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 NCT02516813.

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 15 Oct 2024.

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Clinical Trial NCT02516813 | AzTrials