Phase Ib/II Study of M3814 With Etoposide and Cisplatin in Small Cell Lung Cancer (SCLC) Extensive Disease (ED)

NCT03116971 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: MS100036-0022
• Study Type: interventional
• Target: 2
• Locations: 13 countries
• Sites: 80

Brief Summary

M3814 is an investigational drug under evaluation for treatment of lung cancer. The purpose of the study was to assess the Safety and Efficacy of M3814 in combination with chemotherapy with SCLC ED.

Conditions

Small Cell Lung Cancer

Keywords

M3814, Small Cell Lung Cancer (SCLC), Deoxyribonucleic acid-dependent protein kinase inhibitor, Chemotherapy

Outcome Measures

Primary Outcomes (3)

• Phase Ib: Number of Subjects Experienced Any Dose-Limiting Toxicity (DLT) over the DLT period.

  up to 21 days

• Phase Ib: Determination of Recommended Phase II dose (RP2D) of Escalating Dose of M3814 in Combination With Cisplatin and Etoposide for the Phase II Part of the Study

  up to 11 months

• Phase II: Progression Free Survival (PFS) as Assessed by the Investigator according to RECIST v1.1

  PFS time will be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. The PFS time is defined as the duration from randomization to either first observation of progressive disease (PD) or occurrence of death due to any cause.

  Time from randomization to first assessment of disease progression or death, whichever is earlier, assessed up to 24 months

Secondary Outcomes (47)

• Phase Ib: Number of Subjects with of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths

  From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment

• Phase Ib: Number of Subjects with Abnormal Laboratory Values, Abnormal Vital Signs and Abnormal Electrocardiograms (ECGs)

  From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment

• Phase Ib: Change in Eastern Cooperative Oncology Group performance status (ECOG PS)

  From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment

• Phase Ib: Percentage of Subjects with Objective Response (OR) According to RECIST v1.1

  Post randomization with period tumor evaluations until disease progression or subject withdrawal of consent, irrespective of treatment discontinuation or initiation of another therapy, assessed up to 11 months

• Phase Ib: Duration of Response (DoR) According to RECIST v1.1

  First documented complete response or partial response, whichever is first recorded until the first assessment of disease progression, assessed up to 11 months

Study Arms (2)

M3814 PiC with Etoposide and Cisplatin

EXPERIMENTAL

Participants received M3814 100 milligram (mg) powder in capsule (PiC) orally once daily in combination with Etoposide 100 mg/m\^2 over a 60 minute intravenous infusion on Days 1-3 and Cisplatin 75 milligram per square meter (mg/m\^2) over a 60-minute intravenous infusion on Day 1 for 6 cycles with each cycle lasting 3 weeks (21 days) until progressive disease (PD).

Drug: M3814; Drug: Cisplatin; Drug: Etoposide

M3814 (HME Tablet + PiC) with Etoposide and Cisplatin

EXPERIMENTAL

Participants received M3814 100 mg hot melt extrusion (HME) tablet orally 5 days prior to Day 1 and M3814 100 mg PiC, orally once daily from Day 1 in combination with Etoposide 100 mg/m\^2 over a 60 minute intravenous infusion on Days 1-3 and Cisplatin 75 mg/m\^2 over a 60-minute intravenous infusion on Day 1 for 6 cycles with each cycle lasting 3 weeks (21 days) until PD.

Drug: M3814; Drug: Cisplatin; Drug: Etoposide

Interventions

M3814 DRUG

Participants received M3814 PiC or hot melt extrusion (HME) tablet orally once daily in combination with etoposide (intravenously) and cisplatin for 6 cycles with each cycle lasting 3 weeks (21 days).

Also known as: MSC2490484A, Peposertib

M3814 (HME Tablet + PiC) with Etoposide and Cisplatin; M3814 PiC with Etoposide and Cisplatin

Cisplatin DRUG

Cisplatin 75 milligram per square meter (mg/m\^2) was administered over a 60-minute intravenous infusion on Day 1.

M3814 (HME Tablet + PiC) with Etoposide and Cisplatin; M3814 PiC with Etoposide and Cisplatin

Etoposide DRUG

Etoposide 100 mg/m\^2 over a 60 minute IV infusion on Days 1-3 was administered for 6 cycles with each cycle lasting 3 weeks (21 days).

M3814 (HME Tablet + PiC) with Etoposide and Cisplatin; M3814 PiC with Etoposide and Cisplatin

Eligibility Criteria

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

You may qualify if:

• To be eligible for the study (Phase Ib and Phase II) the participant must fulfill all of the following criteria:
• Male or female participants at least 18 years of age
• Histological or cytological diagnosis of SCLC
• Extensive disease (ie, disease beyond ipsilateral hemithorax, which may include malignant pleural or pericardial effusion or hematogenous metastases \[Tany, Nany, M1a/b; T3-T4, Nany, M0, due to multiple lung nodules or extent of disease that precludes a tolerable radiation field, as judged by the Investigator\])
• Participants eligible for first line platinum-based chemotherapy
• Measurable or evaluable disease according to RECIST v1.1
• Eastern Cooperative Oncology Group performance status (ECOG PS) less than equals to (\<=) 2
• Life expectancy of greater than equals to (≥) 3 months
• Female participants of childbearing potential and male participants with female partners of childbearing potential must be willing to avoid pregnancy Note: Other protocol defined criteria could apply.

You may not qualify if:

• Prior anticancer therapy for extensive disease (ED) SCLC including experimental agents.
• Concurrent use of other anticancer therapy including any investigational agent within 28 days prior to the first dose of the investigational drug M3814.
• Extensive prior radiotherapy (RT) on more than 30% of bone marrow reserves (by Investigator judgment)
• Prior bone marrow/stem cell transplantation within 5 years before study start (Phase II only)
• Major surgical intervention within 28 days prior to the first dose of investigational drug administration. Intervention(s) to establish the diagnosis for SCLC is permitted within 28 days as long as participants are cleared by the medical and surgical teams.
• Poor vital organ functions defined as:
• Bone marrow impairment as evidenced by hemoglobin less than (\<) 9.0 gram per deci liter (g/dL) (5.7 micromole per liter (μmol/L)), absolute neutrophil count \< 1.5 × 109/L, platelets \< 100 × 109/L
• Renal impairment as evidenced by calculated creatinine clearance \< 60 mL/minutes (min) (according to the Cockcroft-Gault formula)
• Liver function abnormality as defined by total bilirubin greater than (\>) 1.5 × upper limit of normal (ULN) or aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \> 2.5 × ULN (participants with liver involvement: a maximum of AST/ALT 5 × ULN)
• Contraindication to the use of etoposide or cisplatin
• Participants currently receiving (or unable to stop using prior to receiving the first dose of investigational drug) medications or herbal supplements known to be potent inhibitors of cytochrome P450 (CYP) 3A and CYP2C19 (unless treatment can be discontinued at least 1 week prior to receiving the first dose of investigational drug) or potent inducers of CYP3A and CYP2C19 (unless treatment can be discontinued at least 3 weeks prior to receiving the first dose of investigational drug). Note: Other protocol defined criteria could apply.

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (80)

Research site

Mesa, Arizona, 85206, United States

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Research site 1

Santa Rosa, California, 95403, United States

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Santa Rosa, California, 95403, United States

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Whittier, California, 90603, United States

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Danbury, Connecticut, 06810, United States

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Norwalk, Connecticut, 06850, United States

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Columbus, Georgia, 31904, United States

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Newnan, Georgia, 30265, United States

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Topeka, Kansas, 66606, United States

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Ashland, Kentucky, 41101, United States

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Billings, Montana, 59101, United States

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Pinehurst, North Carolina, 28374, United States

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Cincinnati, Ohio, 45229, United States

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Portland, Oregon, 97213, United States

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Philadelphia, Pennsylvania, 19124, United States

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Houston, Texas, 77030, United States

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Aalst, 9300, Belgium

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Charleroi, 6000, Belgium

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Edegem, 2650, Belgium

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Ghent, 9000, Belgium

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Libramont, 6800, Belgium

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Liège, 4000, Belgium

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Roeselare, 8800, Belgium

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Yvoir, 5530, Belgium

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Sofia, 1330, Bulgaria

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Sofia, 1407, Bulgaria

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Sofia, 1431, Bulgaria

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Sofia, 1527, Bulgaria

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Sofia, 1632, Bulgaria

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Sofia, 1784, Bulgaria

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Calgary, Alberta, T2N 4N2, Canada

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Saint John, New Brunswick, E2L 4L2, Canada

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London, Ontario, N6A 5W9, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Benešov, 256 01, Czechia

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Olomouc, 775 20, Czechia

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Aalborg, 9100, Denmark

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Herlev, 2730, Denmark

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Odense C, 5000, Denmark

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Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

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Gauting, Bavaria, 82131, Germany

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Nuremberg, Bavaria, 90419, Germany

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Hanover, Lower Saxony, 30625, Germany

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Chemnitz, Saxony, 9113, Germany

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Kiel, Schleswig-Holstein, 24105, Germany

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Lübeck, Schleswig-Holstein, 23538, Germany

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Berlin, 10117, Germany

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Berlin, 10967, Germany

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Budapest, 1121, Hungary

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Budapest, 1121, Hungary

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Budapest, 1125, Hungary

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Farkasgyepű, 8582, Hungary

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Szekszárd, 7100, Hungary

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Szolnok, 5000, Hungary

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Rozzano, Milano, 20089, Italy

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Catania, 95123, Italy

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Genova, 16132, Italy

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Napoli, 80131, Italy

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Ravenna, 48121, Italy

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Reggio Emilia, 42100, Italy

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Roma, 168, Italy

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Torino, 10126, Italy

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Olsztyn, 10-357, Poland

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Poznan, 60-569, Poland

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Warsaw, 02-781, Poland

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Wodzisław Śląski, 44-300, Poland

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Baia Mare, 430291, Romania

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Cluj-Napoca, 400015, Romania

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Cluj-Napoca, 400058, Romania

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Craiova, 200347, Romania

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Timișoara, 300210, Romania

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Badajoz, 6080, Spain

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Madrid, 28040, Spain

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Madrid, 28040, Spain

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Madrid, 28046, Spain

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Madrid, 28050, Spain

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Hull, East Riding Of Yorkshire, HU16 5JQ, United Kingdom

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London, Greater London, W1G 6AD, United Kingdom

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Sheffield, South Yorkshire, S10 2SJ, United Kingdom

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Glasgow, Strathclyde, G12 OYN, United Kingdom

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MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

peposertib; Cisplatin; Etoposide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2017
• First Posted: April 17, 2017
• Study Start: May 25, 2017
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: September 16, 2020

Record last verified: 2020-09

Locations

DE (9); BU (6); IT (8); RO (5); GB (4); PL (4); US (16); HU (6); CA (4); CZ (2); ES (5); DK (3); BE (8)