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

Small Cell Lung Cancer Clinical Trial

Official title:

A Multicenter Study With an Open Label Phase Ib Part Followed by a Randomized, Placebo-controlled, Double-blind, Phase II Part to Evaluate Efficacy, Safety, Tolerability, and PK of M3814 in Combination With Etoposide and Cisplatin in Subjects With Treatment-naïve Small Cell Lung Cancer (SCLC) Extensive Disease (ED)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03116971
• Other study ID #: MS100036-0022
• Status: Terminated
• Phase: Phase 1
• Start date: May 25, 2017
• Est. completion date: March 1, 2018

Study information

• Verified date: September 2020
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: March 1, 2018
• Est. primary completion date: March 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• M3814
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).
• Cisplatin
Cisplatin 75 milligram per square meter (mg/m^2) was administered over a 60-minute intravenous infusion on Day 1.
• Etoposide
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).

Locations

Country	Name	City	State
Belgium	Research site	Aalst
Belgium	Research site	Charleroi
Belgium	Research site	Edegem
Belgium	Research site	Gent
Belgium	Research site	Libramont
Belgium	Research site	Liège
Belgium	Research site	Roeselare
Belgium	Research site	Yvoir
Bulgaria	Reasearch site 5	Sofia
Bulgaria	Research site 1	Sofia
Bulgaria	Research site 2	Sofia
Bulgaria	Research site 3	Sofia
Bulgaria	Research site 4	Sofia
Bulgaria	Research site 6	Sofia
Canada	Research site	Calgary	Alberta
Canada	Research site	London	Ontario
Canada	Research site	St. John	New Brunswick
Canada	Research site	Toronto	Ontario
Czechia	Research site	Benesov
Czechia	Research site	Olomouc
Denmark	Research site	Aalborg
Denmark	Research site	Herlev
Denmark	Research site	Odense C
Germany	Research site 1	Berlin
Germany	Research site 2	Berlin
Germany	Research site	Chemnitz	Saxony
Germany	Research site	Freiburg	Baden Wuerttemberg
Germany	Research site	Gauting	Bavaria
Germany	Research site	Hannover	Lower Saxony
Germany	Research site	Kiel	Schleswig-Holstein
Germany	Research site	Luebeck	Schleswig-Holstein
Germany	Research site	Nuernberg	Bavaria
Hungary	Research site 1	Budapest
Hungary	Research site 2	Budapest
Hungary	Research site 3	Budapest
Hungary	Research site	Farkasgyepu
Hungary	Research site	Szekszard
Hungary	Research site	Szolnok
Italy	Research site	Catania
Italy	Research site	Genova
Italy	Research site	Napoli
Italy	Research site	Ravenna
Italy	Research site	Reggio Emilia
Italy	Research site	Roma
Italy	Research site	Rozzano	Milano
Italy	Research site	Torino
Poland	Research site	Olsztyn
Poland	Research site	Poznan
Poland	Research site	Warszawa
Poland	Research site	Wodzislaw Slaski
Romania	Research site	Baia Mare
Romania	Research site	Cluj-Napoca
Romania	Research site	Cluj-Napoca
Romania	Research site	Craiova
Romania	Research site	Timisoara
Spain	Research site	Badajoz
Spain	Research site 1	Madrid
Spain	Research site 2	Madrid
Spain	Research site 3	Madrid
Spain	Research site 4	Madrid
United Kingdom	Research site	Glasgow	Strathclyde
United Kingdom	Research site	Hull	East Riding Of Yorkshire
United Kingdom	Research site	London	Greater London
United Kingdom	Research site	Sheffield	South Yorkshire
United States	Research site	Ashland	Kentucky
United States	Research site	Billings	Montana
United States	Research site	Cincinnati	Ohio
United States	Research site	Columbus	Georgia
United States	Research site	Danbury	Connecticut
United States	Research site	Houston	Texas
United States	Research site	Mesa	Arizona
United States	Research site	Newnan	Georgia
United States	Research site	Norwalk	Connecticut
United States	Research site	Philadelphia	Pennsylvania
United States	Research site	Pinehurst	North Carolina
United States	Research site	Portland	Oregon
United States	Research site	Santa Rosa	California
United States	Research site 1	Santa Rosa	California
United States	Research site	Topeka	Kansas
United States	Research site	Whittier	California

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Canada,  Czechia,  Denmark,  Germany,  Hungary,  Italy,  Poland,  Romania,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase Ib: Number of Subjects Experienced Any Dose-Limiting Toxicity (DLT) over the DLT period.		up to 21 days
Primary	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
Primary	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	Phase Ib: Number of Subjects with of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	An Adverse Event (AE) is defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment
Secondary	Phase Ib: Number of Subjects with Abnormal Laboratory Values, Abnormal Vital Signs and Abnormal Electrocardiograms (ECGs)	Subjects will be analyzed for vital signs (eg, body temperature, respiratory rate, heart rate, and blood pressure), laboratory parameters and 12-lead ECG recorded at baseline and after administration of M3814. Number of subjects with abnormal values for laboratory values, vital signs and electrocardiograms (ECGs) will be reported.	From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment
Secondary	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
Secondary	Phase Ib: Percentage of Subjects with Objective Response (OR) According to RECIST v1.1	The Objective Response Rate (ORR) is defined as the percentage of subjects whose Best objective response (BOR) is either complete response (CR) or partial response (PR). The ORR will be derived from the BOR according to response evaluation criteria in solid tumors (RECIST) v1.1 as assessed by the Investigator.	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
Secondary	Phase Ib: Duration of Response (DoR) According to RECIST v1.1	The DoR applies only to subjects whose BOR is either CR or PR. The duration is measured from the first documented response (CR or PR, whichever is first recorded) until the first assessment of Progressive Disease (PD).The DoR will be derived from the BOR according to RECIST v1.1 as assessed by the Investigator.	First documented complete response or partial response, whichever is first recorded until the first assessment of disease progression, assessed up to 11 months
Secondary	Phase Ib: Percentage of Subjects With Disease Control	Percentage of subjects with disease control as assessed by best overall response of either CR, PR or Stable Disease (SD) will be reported.	First documented complete response or partial response, whichever is first recorded until the first assessment of disease progression, assessed up to 11 months
Secondary	Phase Ib: Progression Free Survival (PFS) According to RECIST v1.1	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. The PFS will be derived according to RECIST v1.1 as assessed by the Investigator.	Time from randomization to first assessment of disease progression or death, whichever is earlier, assessed up to 11 months
Secondary	Phase Ib: Overall Survival (OS)	The OS time is defined as the date from randomization to death due to any cause.	Time from randomization to death due to any cause, assessed up to 11 months
Secondary	Phase Ib: Area under the concentration-time curve from 0 to 4 hours (AUC 0-4), 0 to 24 hours (AUC 0-24) for M3814, Cisplatin and Etoposide		Day (D) -1, Cycle (C) 1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hours (hrs) post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose, C3D1 Pre-dose and 3.5 hrs post dose
Secondary	Phase Ib: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUC 0-t ) for M3814, Cisplatin and Etoposide		Day (D) -1, Cycle (C) 1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
Secondary	Phase Ib: Maximum Observed Plasma Concentration (Cmax) for M3814, Cisplatin and Etoposide		Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post-dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post-dose, C2D3 Pre-dose
Secondary	Phase Ib: Time to Reach Maximum Plasma Concentration (Tmax) for M3814, Cisplatin and Etoposide		Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post-dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post-dose, C2D3 Pre-dose
Secondary	Phase Ib: Apparent Terminal Half-life (t1/2) for M3814		C1D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hours (hrs) post-dose
Secondary	Phase Ib: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of M3814		C1D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hours (hrs) post-dose
Secondary	Phase Ib: Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of M3814		Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post-dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post-dose, C2D3 Pre-dose
Secondary	Phase Ib: Intravenous (IV) Clearance (CL) of Cisplatin and Etoposide		Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hr post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
Secondary	Phase Ib: Apparent Volume of Distribution Following Extravascular Administration (Vz/f) of M3814		Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
Secondary	Phase Ib: Apparent Volume of Distribution (Vz) of Cisplatin and Etoposide		Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
Secondary	Phase Ib: Terminal rate constant (?z) for M3814, Cisplatin and Etoposide		Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
Secondary	Phase Ib: Changes in Cmax for M3814 Between Day -1 and C2D1		Day (D) -1, Cycle (C) 2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose
Secondary	Phase Ib: Changes in AUC for M3814 Between Day -1 and C2D1		Day (D) -1, Cycle (C) 2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose
Secondary	Phase Ib: Changes in AUC for Etoposide From C1D1 to C1D2, C1D3, and C2D1 (for the first 2 dose levels), or From C1D1 to C2D1 (other dose levels)		Day (D) -1, Cycle (C) 1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose
Secondary	Phase Ib: Changes in Cmax for Etoposide From C1D1 and C2D1		Cycle (C) 1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose
Secondary	Phase Ib: Changes in AUC for Cisplatin From C1D1 to C1D2, C1D3, and C2D1 (for the first 2 dose levels), or From C1D1 to C2D1 (other dose levels)		Day (D) -1, Cycle (C) 1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose
Secondary	Phase Ib: Changes in Cmax for Cisplatin From C1D1 and C2D1		Cycle (C) 1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose
Secondary	Phase II: Overall Survival (OS)		Time from randomization to death due to any cause, assessed up to 24 months
Secondary	Phase II: Percentage of Subjects with Objective Response (OR) According to RECIST v1.1	The Objective Response Rate (ORR) is defined as the proportion of subjects whose Best objective response (BOR) is either complete response (CR) or partial response (PR). The ORR will be derived from the BOR according to response evaluation criteria in solid tumors (RECIST) Version 1.1 as assessed by the Investigator.	Post randomization every 6 weeks up to Week 54 and then every 12 weeks until disease progression or subject withdrawal of consent, irrespective of treatment discontinuation or initiation of another therapy., assessed up to 24 months
Secondary	Phase II: Duration of Response (DoR) According to RECIST v1.1	The DoR applies only to subjects whose BOR is either CR or PR. The duration is measured from the first documented response (CR or PR, whichever is first recorded) until the first assessment of Progressive Disease (PD).The DoR will be derived from the BOR according to RECIST v1.1 as assessed by the Investigator.	First documented complete response or partial response, whichever is first recorded until the first assessment of disease progression, assessed up to 24 months
Secondary	Phase II: Percentage of Subjects With Disease Control	Percentage of subjects with disease control as assessed by best overall response of either CR, PR or Stable Disease (SD) will be reported.	First documented complete response or partial response, whichever is first recorded until the first assessment of disease progression, assessed up to 24 months
Secondary	Phase II: Percentage of Subjects Who Received Prophylactic Cranial Irradiation (PCI) and/or Thorax Irradiation After 6 Cycles of Treatment		After 6 Cycles of treatment, assessed up to 24 months
Secondary	Phase II: Tumor shrinkage From Baseline in target lesions		Post randomization every 6 weeks up to Week 54 and then every 12 weeks until disease progression or subject withdrawal of consent, irrespective of treatment discontinuation or initiation of another therapy., assessed up to 24 months
Secondary	Phase II: Number of subjects with of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths	An Adverse Event (AE) is defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A Serious AE (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.	From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment
Secondary	Phase II: 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
Secondary	Phase II: 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
Secondary	Phase II: Primary Health-Related Quality of Life (HRQoL) Based on Time to Definitive Deterioration (TUDD) as Assessed Using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30)		Screening; Post randomization every 6 weeks up to Week 54 and then every 12 weeks until disease progression or subject withdrawal of consent, irrespective of treatment discontinuation or initiation of another therapy., assessed up to 24 months
Secondary	Phase II: Primary HRQoL based on TUDD Assessed Using EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13)		Screening; Post randomization every 6 weeks up to Week 54 and then every 12 weeks until disease progression or subject withdrawal of consent, irrespective of treatment discontinuation or initiation of another therapy., assessed up to 24 months
Secondary	Phase II: Primary HRQoL based on TUDD Assessed Using European Quality of Life 5- dimensions questionnaire (EQ-5D)		Screening; Post randomization every 6 weeks up to Week 54 and then every 12 weeks until disease progression or subject withdrawal of consent, irrespective of treatment discontinuation or initiation of another therapy., assessed up to 24 months
Secondary	Phase II: Area under the concentration-time curve from 0 to 24 hours (AUC 0-24) for M3814, Cisplatin and Etoposide		C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
Secondary	Phase II: Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC 0-t ) for M3814, Cisplatin and Etoposide		C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
Secondary	Phase II: Maximum Observed Plasma Concentration (Cmax) for M3814, Cisplatin and Etoposide		C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
Secondary	Phase II: Time to Reach Maximum Plasma Concentration (Tmax) for M3814, Cisplatin and Etoposide		C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
Secondary	Phase II: Apparent Terminal Half-life (t1/2) for M3814		C1D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose
Secondary	Phase II: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of M3814		C1D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose
Secondary	Phase II: Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of M3814		C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
Secondary	Phase II: Intravenous (IV) Clearance (CL) of Cisplatin and Etoposide		Time Frame: C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
Secondary	Phase II: Apparent Volume of Distribution Following Extravascular Administration (Vz/f) of M3814		C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
Secondary	Phase II: Apparent Volume of Distribution (Vz) of Cisplatin and Etoposide		C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose