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

NCT ID: NCT04768296

Last Updated: 2024-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-29
• Study Completion Date: 2023-07-21

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.

Conditions

Small-cell Lung Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Safety run-in Part (Dose Level1 [DL 1]): Berzosertib 105 mg/m^2 + Topotecan 1.25 mg/m^2

Participants received Berzosertib at a dose of 105 milligrams per square meter (mg/m\^2 ) intravenously on Day 2 and Day 5 of each 21-daycycle in combination with Topotecan at a dose of 1.25mg/m\^2 intravenously on Days1 through 5 of each 21-day cycle in DL1 of safety run-in part until disease progression or other criteria for study intervention discontinuation are met.

Group Type: EXPERIMENTAL

Berzosertib

Intervention Type: DRUG

Participants received 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 until disease progression or other criteria for study intervention discontinuation are met.

Topotecan

Intervention Type: DRUG

Participants received 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.

Safety run-in Part (DL2) +Main Part: Berzosertib 210 mg/m^2 + Topotecan 1.25 mg/m^2

Participants received Berzosertib at a dose of 210 mg/m\^2 intravenously on Day 2 and Day 5 of each 21-day cycle in combination with Topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in DL 1 and DL 2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met.

Group Type: EXPERIMENTAL

Berzosertib

Intervention Type: DRUG

Participants received 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

Intervention Type: DRUG

Participants received 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.

Interventions

Berzosertib

Participants received 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 until disease progression or other criteria for study intervention discontinuation are met.

Intervention Type: DRUG

Berzosertib

Participants received 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.

Intervention Type: DRUG

Topotecan

Participants received 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.

Intervention Type: DRUG

Other Intervention Names

M6620; M6620

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Locations

Providence Medical Foundation

Santa Rosa, California, United States

St Joseph Heritage Healthcare

Santa Rosa, California, United States

Cotton-O'Neil Clinical Research Center, Hematology and Oncology

Topeka, Kansas, United States

National Cancer Institute

Bethesda, Maryland, United States

Cancer & Hematology Centers of Western Michigan

Grand Rapids, Michigan, United States

MidAmerica Cancer Care

Kansas City, Missouri, United States

NJ Center for Cancer Research

Brick, New Jersey, United States

Southeastern Medical Oncology Center

Goldsboro, North Carolina, United States

FirstHealth of the Carolinas, Inc.

Pinehurst, North Carolina, United States

Summa Health

Akron, Ohio, United States

Toledo Clinic

Toledo, Ohio, United States

Millennium Physicians Association, LLP

Houston, Texas, United States

Centre Hospitalier de l'Ardenne

Arlon, , Belgium

Institut Jules Bordet - Department of Institut Jules Bordet

Brussels, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

AZ Delta

Roeselare, , Belgium

CHU UCL Namur - Mont-Godinne

Yvoir, , Belgium

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, , China

Institut Bergonié

Bordeaux, , 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, , France

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)

Milan, , 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, , Italy

National Cancer Center Hospital

Chūōku, , Japan

Kansai Medical University Hospital

Hirakata-shi, , Japan

National Cancer Center Hospital East

Kashiwa-shi, , Japan

Cancer Institute Hospital of JFCR

Kōtoku, , Japan

Kindai University Hospital

Osaka, , Japan

Kurume University Hospital

Osaka, , Japan

Osaka Medical and Pharmaceutical University Hospital

Takatsuki-shi, , Japan

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

Málaga, , Spain

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Countries

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

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS201923_0050

Trial Awareness and Transparency website

https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

http://www.DDRiver-trials.com

DDRiver website

Other Identifiers

2020-004231-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MS201923_0050

Identifier Type: -

Identifier Source: org_study_id