Clinical Trials /

Berzosertib + Topotecan in Relapsed Platinum-Resistant Small-Cell Lung Cancer (DDRiver SCLC 250)

NCT04768296

Description:

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.

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Berzosertib + Topotecan in Relapsed Platinum-Resistant Small-Cell Lung Cancer (DDRiver SCLC 250)
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: MS201923_0050
  • SECONDARY ID: 2020-004231-25
  • NCT ID: NCT04768296

Conditions

  • Small-cell Lung Cancer

Interventions

DrugSynonymsArms
BerzosertibM6620Berzosertib + Topotecan
BerzosertibM6620Berzosertib + Topotecan
TopotecanBerzosertib + Topotecan

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Berzosertib + TopotecanExperimentalIn 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.
  • Berzosertib
  • Berzosertib
  • Topotecan

Eligibility 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 4 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Main Part: Overall Survival (OS)
Time Frame:From first administration of study intervention up to 15 months
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Safety Run-in Part: Overall Survival (OS)
Time Frame:From first administration of study intervention up to 15 months
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:EMD Serono Research & Development Institute, Inc.

Trial Keywords

  • M6620
  • Berzosertib
  • Solid Tumor
  • Topotecan
  • Ataxia telangiectasia mutated and Rad3-related
  • Platinum-resistant Small-Cell Lung Cancer
  • DDRiver

Last Updated

February 24, 2021