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

Merck KGaA (EMD Serono)

Status and phase: Terminated; Phase 1

Conditions: Small Cell Lung Cancer

Treatments: Drug: M3814; Drug: Etoposide; Drug: Cisplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT03116971

MS100036-0022

Details and patient eligibility

About

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.

Full description

The study was intended to be a phase I/II trial, but the study never moved forward to Phase II due to recruitment challenges.

Enrollment: 2 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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.

Exclusion criteria

Participants are not eligible for the study if they fulfill any of the following exclusion criteria:

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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2 participants in 2 patient groups

M3814 PiC with Etoposide and Cisplatin

Experimental group

Description:

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).

Treatment:

Drug: Etoposide

Drug: Cisplatin

Drug: M3814

M3814 (HME Tablet + PiC) with Etoposide and Cisplatin

Experimental group

Description:

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.

Treatment:

Drug: Etoposide

Drug: Cisplatin

Drug: M3814