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

Small-cell Lung Cancer Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT04768296
• Other study ID #: MS201923_0050
• Secondary ID: 2020-004231-25
• Status: Completed
• Phase: Phase 2
• Start date: March 29, 2021
• Est. completion date: July 21, 2023

Study information

• Verified date: August 2023
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: July 21, 2023
• Est. primary completion date: July 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Carcinoma
• Small-cell Lung Cancer

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
Belgium	Centre Hospitalier de l'Ardenne	Arlon
Belgium	Institut Jules Bordet - Department of Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	AZ Delta	Roeselare
Belgium	CHU UCL Namur - Mont-Godinne	Yvoir
China	Beijing Cancer Hospital	Beijing
China	Jilin Cancer Hospital	Changchun
China	Sichuan Cancer Hospital	Chengdu
China	West China Hospital, Sichuan University	Chengdu
China	Jiangsu Province Hospital	Nanjing
China	Liaoning Cancer Hospital & Institute	Shenyang
China	Union Hospital of Tongji Medical College, Huazhong University of Science and Technology	Wuhan
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an
China	The First Affiliated Hospital of Zhejiang University school of medicine	Zhejiang
France	Institut Bergonié	Bordeaux cedex
France	Centre Hospitalier Intercommunal de Créteil - Service de Pneumologie	Créteil
France	Hopital Albert Calmette - CHU Lille - service de pneumologie et immuno allergologie	Lille
France	CHU Poitiers - Hôpital la Milétrie - service d'oncologie médicale	Poitiers
France	CHU Nantes - Hôpital Guillaume et René Laënnec - Service de Pneumologie	Saint-Herblain
France	CHU de Strasbourg - Nouvel Hôpital Civil - Service de Pneumologie	Strasbourg
Italy	IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST	Meldola
Italy	Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)	Milano
Italy	Azienda Ospedaliero Universitaria Pisana (Presidio di Cisanello)	Pisa
Italy	Istituto Nazionale Tumori Regina Elena IRCCS	Roma
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica	Rome
Japan	National Cancer Center Hospital	Chuo-ku
Japan	Kansai Medical University Hospital	Hirakata-shi
Japan	National Cancer Center Hospital East	Kashiwa-shi
Japan	Cancer Institute Hospital of JFCR	Koto-ku
Japan	Kindai University Hospital	Osaka
Japan	Kurume University Hospital	Osaka
Japan	Osaka Medical and Pharmaceutical University Hospital	Takatsuki-shi
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria - Oncology Service	Malaga
Spain	Hospital Universitario Virgen de la Victoria	Malaga
Spain	Hospital Universitario Virgen Macarena	Sevilla
United States	Summa Health	Akron	Ohio
United States	National Cancer Institute	Bethesda	Maryland
United States	NJ Center for Cancer Research	Brick	New Jersey
United States	Southeastern Medical Oncology Center	Goldsboro	North Carolina
United States	Cancer & Hematology Centers of Western Michigan	Grand Rapids	Michigan
United States	Millennium Physicians Association, LLP	Houston	Texas
United States	MidAmerica Cancer Care	Kansas City	Missouri
United States	FirstHealth of the Carolinas, Inc.	Pinehurst	North Carolina
United States	Providence Medical Foundation	Santa Rosa	California
United States	St Joseph Heritage Healthcare	Santa Rosa	California
United States	Toledo Clinic	Toledo	Ohio
United States	Cotton-O'Neil Clinical Research Center, Hematology and Oncology	Topeka	Kansas

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Belgium,  China,  France,  Italy,  Japan,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Main Part: Objective Response (OR) according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 as assessed by Independent Review Committee (IRC)		From first administration of study intervention up to 15 months
Primary	Safety Run-in Part: Number of Participants With Dose Limiting Toxicities (DLTs)		Up to Cycle 1 Day 21 (each cycle is of 21 days)
Primary	Safety Run-in Part: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-Related TEAEs		From first administration of study intervention up to 15 months
Primary	Safety Run-in Part: Number of Participants with Clinically Significant Changes From Baseline in Vital Signs, 12-Lead Electrocardiogram (ECG) Findings and Laboratory Parameters		From first administration of study intervention up to 15 months
Secondary	Main Part: Duration of Response (DoR) according to RECIST version 1.1 as assessed by IRC		From first administration of study intervention up to 15 months
Secondary	Main Part: Progression-free Survival (PFS) according to RECIST version 1.1 as assessed by IRC		From first administration of study intervention up to 15 months
Secondary	Main Part: Overall Survival (OS)		From first administration of study intervention up to 15 months
Secondary	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)		Baseline, Safety follow-up (up to 15 months)
Secondary	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)		Baseline, Safety follow-up (up to 15 months)
Secondary	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)		Baseline, Safety follow-up (up to 15 months)
Secondary	Main Part: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-Related TEAEs		From first administration of study intervention up to 15 months
Secondary	Main Part: Number of Participants with Clinically Significant Changes From Baseline in Vital Signs, 12-Lead Electrocardiogram (ECG) Findings and Laboratory Parameters		From first administration of study intervention up to 15 months
Secondary	Safety Run-in Part: Objective response according to RECIST version 1.1 as assessed by the Investigator		From first administration of study intervention up to 15 months
Secondary	Safety Run-in Part: Duration of Response (DoR) according to RECIST version 1.1 as assessed by the Investigator		From first administration of study intervention up to 15 months
Secondary	Safety Run-in Part: Progression-free Survival (PFS) according to RECIST version 1.1 as assessed by the Investigator		From first administration of study intervention up to 15 months
Secondary	Safety Run-in Part: Overall Survival (OS)		From first administration of study intervention up to 15 months
Secondary	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)		Baseline, Safety follow-up (up to 15 months)
Secondary	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)		Baseline, Safety follow-up (up to 15 months)
Secondary	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)		Baseline, Safety follow-up (up to 15 months)
Secondary	Safety Run-in Part: Area Under the Plasma Concentration-Time Curve from Time Zero to the Last Sampling Time (AUC0-tlast) of Berzosertib		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)
Secondary	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		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)
Secondary	Safety Run-in Part: Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of Berzosertib		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)
Secondary	Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of Berzosertib		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)
Secondary	Safety Run-in Part: Area Under the Plasma Concentration-Time Curve from Time Zero to 48 Hours (AUC0-48h) of Berzosertib		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)
Secondary	Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve from Time Zero to 48 Hours (AUC0-48h/Dose) of Berzosertib		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)
Secondary	Safety Run-in Part: Area Under the Plasma Concentration-Time Curve from Time Zero to 72 Hours (AUC0-72h) of Berzosertib		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)
Secondary	Safety Run-in Part: Dose Normalized Area Under the Plasma Concentration-Time Curve from Time Zero to 72 Hours (AUC0-72h/Dose) of Berzosertib		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)
Secondary	Safety Run-in Part: Maximum Observed Plasma Concentration (Cmax) of Berzosertib		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)
Secondary	Safety Run-in Part: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of Berzosertib		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)
Secondary	Safety Run-in Part: Plasma Observed Concentration at the End of the Infusion (Ceoi) of Berzosertib		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)
Secondary	Safety Run-in Part: Plasma Observed Concentration Immediately Before Next Dosing (Ctrough) of Berzosertib		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)
Secondary	Safety Run-in Part: Apparent Total Body Clearance (CL) of Berzosertib		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)
Secondary	Safety Run-in Part: Metabolic Ratio of Maximum Observed Plasma Concentration (MR[Cmax]) of Berzosertib		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)
Secondary	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		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)
Secondary	Safety Run-in Part: Metabolic Ratio Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (MR[AUC0-inf]) of Berzosertib		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)
Secondary	Safety Run-in Part: Accumulation Ratio for Maximum Observed Plasma Concentration [Racc(Cmax)] of Berzosertib		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)
Secondary	Safety Run-in Part: Time to Reach the Maximum Observed Plasma Concentration (tmax) of Berzosertib		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)
Secondary	Safety Run-in Part: Apparent Terminal Half-life (t1/2) of Berzosertib		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)
Secondary	Safety Run-in Part: Last Sampling Time (tlast) of Berzosertib		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)
Secondary	Safety Run-in Part: Apparent Volume of Distribution (Vz) of Berzosertib		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)

External Links

•   DDRiver website
•   Trial Awareness and Transparency website
•   US Medical Information website, Medical Resources