An Open Label, Phase Ia/Ib Trial of the DNA-PK Inhibitor MSC2490484A in Combination With Radiotherapy in Patients With Advanced Solid Tumors
Status: Completed
Location: See all (26) locations...
Intervention Type: Drug, Radiation
Study Type: Interventional
Study Phase: Phase 1
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 + cisplatin).
Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:
• 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)
• 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.
Locations
United States
California
Research site
Fresno
Florida
Holy Cross Hospital Inc.
Fort Lauderdale
University of Miami Miller School of Medicine
Miami
Montana
Research site
Billings
New York
Montefiore Medical Center PRIME
Bronx
Memorial Sloan Kettering Cancer Center
New York
Pennsylvania
Thomas Jefferson University Hospital
Philadelphia
Texas
Research site
Houston
Washington
Research site
Tacoma
Other Locations
Belgium
Research site
Leuven
Denmark
Rigshospitalet - PARENT
Copenhagen
Herlev Hospital - PARENT
Herlev
Germany
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
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
Tuebingen
Netherlands
Antoni van Leeuwenhoek Ziekenhuis
Amsterdam
Research site
Amsterdam
Norway
Research site
Oslo
Sweden
Karolinska universitetssjukhuset - Solna - Radiumhemmet (onkologi)
Solna
Switzerland
Universitaetsspital Zuerich - Parent
Zuerich
Time Frame
Start Date: 2015-09-15
Completion Date: 2021-11-19
Participants
Target number of participants: 52
Treatments
Experimental: Phase 1a (Arm A): M3814 Capsule (100 mg) + RT
Participants 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 \[F/W\]).
Experimental: Phase 1a (Arm A): M3814 Capsule (200 mg) + RT
Participants 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).
Experimental: Phase 1a (Arm A): M3814 Capsule (300 mg) + RT
Participants 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).
Experimental: Phase 1a (Arm A): M3814 Capsule (400 mg) + RT
Participants 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).
Experimental: Phase 1a (Arm A): M3814 Tablet (100 mg) + RT
Participants 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).
Experimental: Phase 1a (Arm A): M3814 Tablet (200 mg) + RT
Participants 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).
Experimental: Phase 1a (Arm A): M3814 Tablet (300 mg) + RT
Participants 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).
Experimental: Phase 1a (Arm B): M3814 Capsule (50 mg) + CRT
Participants 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).
Experimental: Phase 1a (Arm B): M3814 Tablet (100 mg) + CRT
Participants 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).
Experimental: Ancillary cPoP: M3814 Capsule (100 mg) + RT
Participants 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.
Experimental: Ancillary cPOP: M3814 Capsule (200 mg) + RT
Participants 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.
Experimental: Ancillary cPOP: M3814 Capsule (400 mg) + RT
Participants 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
Authors
Sponsors
Collaborators: Merck KGaA, Darmstadt, Germany
Leads: EMD Serono Research & Development Institute, Inc.