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Trial record 1 of 18 for:    berzosertib
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Berzosertib + Topotecan in Relapsed Platinum-Resistant Small-Cell Lung Cancer (DDRiver SCLC 250)

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: NCT04768296
Recruitment Status : Active, not recruiting
First Posted : February 24, 2021
Last Update Posted : April 26, 2023
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Study Description
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Brief Summary:
The main purpose of this study is to assess efficacy, safety, tolerability and pharmacokinetics (PK) of Berzosertib in combination with Topotecan in participants with relapsed, platinum-resistant small-cell lung cancer (SCLC). This study will be conducted in two parts: safety run-in part and main part. The safety run-in part will be conducted in Japan.

Condition or disease Intervention/treatment Phase
Small-cell Lung Cancer Drug: Berzosertib Drug: Topotecan Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Open-label, Single-arm Study of Berzosertib (M6620) in Combination With Topotecan in Participants With Relapsed Platinum-resistant Small-Cell Lung Cancer (DDRiver SCLC 250)
Actual Study Start Date : March 29, 2021
Estimated Primary Completion Date : August 8, 2023
Estimated Study Completion Date : May 23, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Berzosertib + Topotecan
In Japan, a Safety Run-in Part will be conducted. In case safety and tolerability is confirmed in the Safety Run-in part, Japanese participants will enroll in the Main Part of the Phase 2. Both in the Safety Run-in and Main Part of the Phase 2, participants will receive berzosertib and topotecan until disease progression or other criteria for study intervention discontinuation are met.
 Drug: Berzosertib
Participants with advanced solid tumors, for which no effective standard therapy exists, or standard therapy has failed will receive Berzosertib at a dose of 105 milligrams per square meter (mg/m^2) intravenously on Day 2 and Day 5 of each 21-day cycle in DL1 of safety run-in part.
Other Name: M6620

Drug: Berzosertib
Participants with relapsed, platinum-resistant SCLC will receive Berzosertib at a dose of 210 mg/m^2 intravenously on Day 2 and Day 5 of each 21-day cycle in DL2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met.
Other Name: M6620

Drug: Topotecan
Participants who have advanced solid tumors, for which no effective standard therapy exists, or standard therapy has failed or who have relapsed, platinum-resistant SCLC will receive Topotecan at a dose of 1.25 mg/m^2 intravenously on Days 1 through 5 of each 21-day cycle in DL1 and DL2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met.


Outcome Measures
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Primary Outcome Measures :
  1. Main Part: Objective Response (OR) according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 as assessed by Independent Review Committee (IRC) [ Time Frame: From first administration of study intervention up to 15 months ]
  2. Safety Run-in Part: Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Up to Cycle 1 Day 21 (each cycle is of 21 days) ]
  3. Safety Run-in Part: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-Related TEAEs [ Time Frame: From first administration of study intervention up to 15 months ]
  4. Safety Run-in Part: Number of Participants with Clinically Significant Changes From Baseline in Vital Signs, 12-Lead Electrocardiogram (ECG) Findings and Laboratory Parameters [ Time Frame: From first administration of study intervention up to 15 months ]

Secondary Outcome Measures :
  1. Main Part: Duration of Response (DoR) according to RECIST version 1.1 as assessed by IRC [ Time Frame: From first administration of study intervention up to 15 months ]
  2. Main Part: Progression-free Survival (PFS) according to RECIST version 1.1 as assessed by IRC [ Time Frame: From first administration of study intervention up to 15 months ]
  3. Main Part: Overall Survival (OS) [ Time Frame: From first administration of study intervention up to 15 months ]
  4. Main Part: Change From Baseline in Physical Functioning Measured by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) [ Time Frame: Baseline, Safety follow-up (up to 15 months) ]
  5. Main Part: Change From Baseline in Cough, Dyspnea and Chest Pain Measured by European Organization for the Research and Treatment of Cancer Quality of Life and Lung Cancer Specific Questionnaire (EORTC QLQ-LC13) [ Time Frame: Baseline, Safety follow-up (up to 15 months) ]
  6. Main Part:Change From Baseline in Health State as Measured by Visual Analogue Scale (VAS) Component of European Quality of Life 5-dimensions 5 Level Scale (EQ-5D-5L) [ Time Frame: Baseline, Safety follow-up (up to 15 months) ]
  7. Main Part: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-Related TEAEs [ Time Frame: From first administration of study intervention up to 15 months ]
  8. Main Part: Number of Participants with Clinically Significant Changes From Baseline in Vital Signs, 12-Lead Electrocardiogram (ECG) Findings and Laboratory Parameters [ Time Frame: From first administration of study intervention up to 15 months ]
  9. Safety Run-in Part: Objective response according to RECIST version 1.1 as assessed by the Investigator [ Time Frame: From first administration of study intervention up to 15 months ]
  10. Safety Run-in Part: Duration of Response (DoR) according to RECIST version 1.1 as assessed by the Investigator [ Time Frame: From first administration of study intervention up to 15 months ]
  11. Safety Run-in Part: Progression-free Survival (PFS) according to RECIST version 1.1 as assessed by the Investigator [ Time Frame: From first administration of study intervention up to 15 months ]
  12. Safety Run-in Part: Overall Survival (OS) [ Time Frame: From first administration of study intervention up to 15 months ]
  13. Safety Run-in Part: Change From Baseline in Cough, Dyspnea and Chest Pain Measured by European Organization for the Research and Treatment of Cancer Quality of Life and Lung Cancer Specific Questionnaire (EORTC QLQ-LC13) [ Time Frame: Baseline, Safety follow-up (up to 15 months) ]
  14. Safety Run-in Part: Change From Baseline in Physical Functioning Measured by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) [ Time Frame: Baseline, Safety follow-up (up to 15 months) ]
  15. Safety Run-in Part:Change From Baseline in Health State as Measured by Visual Analogue Scale (VAS) Component of European Quality of Life 5-dimensions 5 Level Scale (EQ-5D-5L) [ Time Frame: Baseline, Safety follow-up (up to 15 months) ]
  16. Safety Run-in Part: Area Under the Plasma Concentration-Time Curve from Time Zero to the Last Sampling Time (AUC0-tlast) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  17. Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve from Time Zero to the Last Sampling Time (AUC0-tlast/Dose) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  18. Safety Run-in Part: Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  19. Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  20. Safety Run-in Part: Area Under the Plasma Concentration-Time Curve from Time Zero to 48 Hours (AUC0-48h) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  21. Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve from Time Zero to 48 Hours (AUC0-48h/Dose) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  22. Safety Run-in Part: Area Under the Plasma Concentration-Time Curve from Time Zero to 72 Hours (AUC0-72h) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  23. Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve from Time Zero to 72 Hours (AUC0-72h/Dose) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  24. Safety Run-in Part: Maximum Observed Plasma Concentration (Cmax) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  25. Safety Run-in Part: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  26. Safety Run-in Part: Plasma Observed Concentration at the End of the Infusion (Ceoi) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  27. Safety Run-in Part: Plasma Observed Concentration Immediately Before Next Dosing (Ctrough) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  28. Safety Run-in Part: Apparent Total Body Clearance (CL) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  29. Safety Run-in Part: Metabolic Ratio of Maximum Observed Plasma Concentration (MR[Cmax]) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  30. Safety Run-in Part: Metabolic Ratio of Area Under the Plasma Concentration-Time Curve from Time Zero to the Last Sampling Time (MR[AUC0-tlast]) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  31. Safety Run-in Part: Metabolic Ratio Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (MR[AUC0-inf]) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  32. Safety Run-in Part: Accumulation Ratio for Maximum Observed Plasma Concentration [Racc(Cmax)] of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  33. Safety Run-in Part: Time to Reach the Maximum Observed Plasma Concentration (tmax) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  34. Safety Run-in Part: Apparent Terminal Half-life (t1/2) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  35. Safety Run-in Part: Last Sampling Time (tlast) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]
  36. Safety Run-in Part: Apparent Volume of Distribution (Vz) of Berzosertib [ Time Frame: 23 hours post-dose on Cycle 1 Day 3 and 47 hours post-dose on Cycle 1 Day 4 (each cycle is of 21 days) ]

Eligibility Criteria
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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:

  • Dose level 1 participants with histologically proven advanced solid tumors, for which no effective standard therapy exists, or standard therapy has failed or cannot be tolerated
  • Dose level 1 participants with Eastern Cooperative Oncology Group Performance Status (ECOG PS) less than or equal to (<=) 1 and Karnofsky Scale greater than or equal to (>=) 70 percent (%)
  • Dose level 2 and main part participants with ECOG PS <= 2 and Karnofsky Scale >= 60%
  • Dose level 2 and main part participants with histologically confirmed SCLC
  • Dose level 2 and main part participants with radiologically confirmed progression after first-line or chemoradiation platinum-based treatment (carboplatin or cisplatin), with or without immunotherapy, for treatment of limited or extensive stage SCLC, with a Platinum-free interval (PFI) less than (<) 90 days. The PFI is measured by the elapsed time from the last day of the regimen of a platinum-based treatment until the first day of documented disease progression
  • Dose level 2 and main part participants with measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (RECISTv1.1) at Screening. Evidence of measurable disease must be confirmed by the IRC prior to start of treatment
  • Tumor tissue provision: archival (collected within 12 months before date of informed consent form [ICF]) signature for Screening) or fresh biopsy specimen, if medically feasible
  • Have adequate hematologic and renal function
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria:

  • Clinically relevant (that is [i.e.], active), uncontrolled intercurrent illness including, but not limited to, severe active infection including, severe acute respiratory syndrome coronavirus-2 infection/coronavirus disease 2019, immune deficiencies, uncontrolled diabetes, uncontrolled arterial hypertension, symptomatic congestive heart failure (New York Heart Association Classification greater than or equal to [>=] Class III), unstable angina pectoris, myocardial infarction, uncontrolled cardiac arrhythmia, cerebral vascular accident/stroke. Calculated corrected QT interval (QTc) average (using the Fridericia correction calculation) of greater than [>] 450 millisecond (msec) for males and > 470 msec for females. Any psychiatric illness/social situations that would limit compliance with study requirements
  • Unstable brain metastases; however, participants with known brain metastases may be enrolled in this clinical study if they are clinically stable (without evidence of progression by imaging for at least 2 weeks prior to the first study intervention dose and any neurologic symptoms have returned to baseline), have no evidence of new brain metastases, and are on a stable or decreasing dose of steroids for at least 14 days prior to study intervention Participants with carcinomatous meningitis are excluded regardless of clinical stability. Screening central nervous system imaging is not mandatory
  • Prior malignant disease within the last 3 years. Exceptions include fully resected basal cell carcinoma of the skin or squamous cell carcinoma of the skin, in situ cervical cancer, fully resected ductal carcinoma in situ of the breast, superficial or noninvasive bladder cancer, and Stage IA, Grade I endometrioid endometrial cancer with no myometrial invasion, that has undergone curative therapy. Participants with other localized malignancies treated with curative intent need to be discussed with the Medical Monitor
  • Participants not recovered from adverse events (AEs) Grade > 1 from prior anticancer therapies, including surgeries. Exception: Grade 2 AEs not constituting a safety risk (for example [e.g.], alopecia), based on the Investigator's judgment; must consult with the medical Monitor prior to enrollment.
  • Other protocol defined exclusion criteria could apply
Contacts and Locations
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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): NCT04768296


Locations
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Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Investigators
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Study Director: Medical Responsible Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
More Information
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Additional Information:

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Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT04768296    
Other Study ID Numbers: MS201923_0050
2020-004231-25 ( EudraCT Number )
First Posted: February 24, 2021    Key Record Dates
Last Update Posted: April 26, 2023
Last Verified: April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
URL: https://bit.ly/IPD21

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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. ):
M6620
Berzosertib
Solid Tumor
Topotecan
 Ataxia telangiectasia mutated and Rad3-related
Platinum-resistant Small-Cell Lung Cancer
DDRiver
Additional relevant MeSH terms:
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Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
 Carcinoma, Bronchogenic
Bronchial Neoplasms
Topotecan
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents