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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03116971
Recruitment Status : Terminated (The study has been terminated because of low recruitment rate of participants and also due to change in focus of the study.)
First Posted : April 17, 2017
Last Update Posted : February 21, 2019
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

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

Condition or disease Intervention/treatment Phase
Small Cell Lung Cancer Drug: M3814 Drug: Cisplatin Drug: Etoposide Phase 1

Detailed 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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)
Actual Study Start Date : May 25, 2017
Actual Primary Completion Date : March 1, 2018
Actual Study Completion Date : March 1, 2018


Arm Intervention/treatment
Experimental: M3814 PiC with with Etoposide and Cisplatin
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
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).
Other Name: MCS2490484A

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

Drug: 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).

Experimental: M3814 (HME Tablet + PiC) with Etoposide and Cisplatin
Participants received M3814 100 mg hot melt extrusion (HME) tablet orally on Day 0 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
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).
Other Name: MCS2490484A

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

Drug: 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).




Primary Outcome Measures :
  1. Phase Ib: Number of Subjects Experienced Any Dose-Limiting Toxicity (DLT) over the DLT period. [ Time Frame: up to 21 days ]
  2. 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 [ Time Frame: up to 11 months ]
  3. Phase II: Progression Free Survival (PFS) as Assessed by the Investigator according to RECIST v1.1 [ Time Frame: Time from randomization to first assessment of disease progression or death, whichever is earlier, assessed up to 24 months ]
    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.


Secondary Outcome Measures :
  1. Phase Ib: Number of Subjects with of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths [ Time Frame: From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment ]
    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.

  2. Phase Ib: Number of Subjects with Abnormal Laboratory Values, Abnormal Vital Signs and Abnormal Electrocardiograms (ECGs) [ Time Frame: From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment ]
    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.

  3. Phase Ib: Change in Eastern Cooperative Oncology Group performance status (ECOG PS) [ Time Frame: From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment ]
  4. Phase Ib: Percentage of Subjects with Objective Response (OR) According to RECIST v1.1 [ Time Frame: 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 ]
    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.

  5. Phase Ib: Duration of Response (DoR) According to RECIST v1.1 [ Time Frame: First documented complete response or partial response, whichever is first recorded until the first assessment of disease progression, assessed up to 11 months ]
    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.

  6. Phase Ib: Percentage of Subjects With Disease Control [ Time Frame: First documented complete response or partial response, whichever is first recorded until the first assessment of disease progression, assessed up to 11 months ]
    Percentage of subjects with disease control as assessed by best overall response of either CR, PR or Stable Disease (SD) will be reported.

  7. Phase Ib: Progression Free Survival (PFS) According to RECIST v1.1 [ Time Frame: Time from randomization to first assessment of disease progression or death, whichever is earlier, assessed up to 11 months ]
    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.

  8. Phase Ib: Overall Survival (OS) [ Time Frame: Time from randomization to death due to any cause, assessed up to 11 months ]
    The OS time is defined as the date from randomization to death due to any cause.

  9. 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 [ Time Frame: 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 ]
  10. Phase Ib: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUC 0-t ) for M3814, Cisplatin and Etoposide [ Time Frame: 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 ]
  11. Phase Ib: Maximum Observed Plasma Concentration (Cmax) for M3814, Cisplatin and Etoposide [ Time Frame: 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 ]
  12. Phase Ib: Time to Reach Maximum Plasma Concentration (Tmax) for M3814, Cisplatin and Etoposide [ Time Frame: 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 ]
  13. Phase Ib: Apparent Terminal Half-life (t1/2) for M3814 [ Time Frame: C1D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hours (hrs) post-dose ]
  14. Phase Ib: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of M3814 [ Time Frame: C1D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hours (hrs) post-dose ]
  15. Phase Ib: Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of M3814 [ Time Frame: 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 ]
  16. Phase Ib: Intravenous (IV) Clearance (CL) of Cisplatin and Etoposide [ Time Frame: 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 ]
  17. Phase Ib: Apparent Volume of Distribution Following Extravascular Administration (Vz/f) of M3814 [ Time Frame: 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 ]
  18. Phase Ib: Apparent Volume of Distribution (Vz) of Cisplatin and Etoposide [ Time Frame: 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 ]
  19. Phase Ib: Terminal rate constant (λz) for M3814, Cisplatin and Etoposide [ Time Frame: 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 ]
  20. Phase Ib: Changes in Cmax for M3814 Between Day -1 and C2D1 [ Time Frame: 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 ]
  21. Phase Ib: Changes in AUC for M3814 Between Day -1 and C2D1 [ Time Frame: 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 ]
  22. 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) [ Time Frame: 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 ]
  23. Phase Ib: Changes in Cmax for Etoposide From C1D1 and C2D1 [ Time Frame: 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 ]
  24. 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) [ Time Frame: 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 ]
  25. Phase Ib: Changes in Cmax for Cisplatin From C1D1 and C2D1 [ Time Frame: 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 ]
  26. Phase II: Overall Survival (OS) [ Time Frame: Time from randomization to death due to any cause, assessed up to 24 months ]
  27. Phase II: Percentage of Subjects with Objective Response (OR) According to RECIST v1.1 [ Time Frame: 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 ]
    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.

  28. Phase II: Duration of Response (DoR) According to RECIST v1.1 [ Time Frame: First documented complete response or partial response, whichever is first recorded until the first assessment of disease progression, assessed up to 24 months ]
    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.

  29. Phase II: Percentage of Subjects With Disease Control [ Time Frame: First documented complete response or partial response, whichever is first recorded until the first assessment of disease progression, assessed up to 24 months ]
    Percentage of subjects with disease control as assessed by best overall response of either CR, PR or Stable Disease (SD) will be reported.

  30. Phase II: Percentage of Subjects Who Received Prophylactic Cranial Irradiation (PCI) and/or Thorax Irradiation After 6 Cycles of Treatment [ Time Frame: After 6 Cycles of treatment, assessed up to 24 months ]
  31. Phase II: Tumor shrinkage From Baseline in target lesions [ Time Frame: 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 ]
  32. Phase II: Number of subjects with of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths [ Time Frame: From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment ]
    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.

  33. Phase II: Number of Subjects with Abnormal Laboratory Values, Abnormal Vital Signs and Abnormal Electrocardiograms (ECGs) [ Time Frame: From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment ]
  34. Phase II: Change in Eastern Cooperative Oncology Group performance status (ECOG PS) [ Time Frame: From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment ]
  35. 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) [ Time Frame: 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 ]
  36. Phase II: Primary HRQoL based on TUDD Assessed Using EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) [ Time Frame: 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 ]
  37. Phase II: Primary HRQoL based on TUDD Assessed Using European Quality of Life 5- dimensions questionnaire (EQ-5D) [ Time Frame: 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 ]
  38. Phase II: Area under the concentration-time curve from 0 to 24 hours (AUC 0-24) for M3814, 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 ]
  39. Phase II: Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC 0-t ) for M3814, 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 ]
  40. Phase II: Maximum Observed Plasma Concentration (Cmax) for M3814, 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 ]
  41. Phase II: Time to Reach Maximum Plasma Concentration (Tmax) for M3814, 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 ]
  42. Phase II: Apparent Terminal Half-life (t1/2) for M3814 [ Time Frame: C1D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose ]
  43. Phase II: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of M3814 [ Time Frame: C1D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose ]
  44. Phase II: Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of M3814 [ 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 ]
  45. Phase II: Intravenous (IV) Clearance (CL) of Cisplatin and Etoposide [ Time Frame: 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 ]
  46. Phase II: Apparent Volume of Distribution Following Extravascular Administration (Vz/f) of M3814 [ 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 ]
  47. Phase II: Apparent Volume of Distribution (Vz) 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

To be eligible for the study (Phase Ib and Phase II) the subject must fulfill all of the following criteria:

  • Male or female subjects 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])
  • Subjects 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 subjects of childbearing potential and male subjects with female partners of childbearing potential must be willing to avoid pregnancy Note: Other protocol defined criteria could apply.

Exclusion Criteria:

Subjects 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 subjects 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 (subjects with liver involvement: a maximum of AST/ALT 5 × ULN)
  • Contraindication to the use of etoposide or cisplatin
  • Subjects 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03116971


  Show 80 Study Locations
Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Investigators
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Study Director: Medical Responsible Merck KGaA, Darmstadt, Germany

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Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT03116971     History of Changes
Other Study ID Numbers: MS100036-0022
First Posted: April 17, 2017    Key Record Dates
Last Update Posted: February 21, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
M3814, Small Cell Lung Cancer (SCLC), Deoxyribonucleic acid-dependent protein kinase inhibitor, Chemotherapy
Additional relevant MeSH terms:
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Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Cisplatin
Etoposide
Etoposide phosphate
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Molecular Mechanisms of Pharmacological Action