A Safety, Tolerability and Preliminary Efficacy Evaluation of CC-90011 Given in Combination With Cisplatin and Etoposide in Subjects With First Line, Extensive Stage Small Cell Lung Cancer

NCT03850067 | Completed Phase 1 DMC

• 3 other identifiers: CC-90011-SCLC-001U1111-1228-20672018-002799-42
• Study Type: interventional
• Target: 90
• Locations: 3 countries
• Sites: 13

Brief Summary

CC-90011-SCLC-001 is a multicenter, Phase 1b, open-label, dose finding study to assess the safety, tolerability, and preliminary efficacy of CC-90011 given concurrently and sequentially to standard of care platinum-based, cisplatin and etoposide, carboplatin and etoposide and/or etoposide and Nivolumab to subjects with first line ES SCLC. The dose finding part of the study will explore escalating oral doses of CC-90011 in combination with cisplatin, etoposide and/or carboplatin with or without Nivolumab (chemotherapy), to determine the maximum tolerated dose of CC- 90011 in combination with chemotherapy with or without Nivolumab to subjects with first line ES SCLC.

Conditions

Small Cell Lung Carcinoma

Keywords

Safety; CC-90011; Extensive stage small cell lung cancer

Outcome Measures

Primary Outcomes (3)

• Dose-Limiting Toxicity (DLT)

  A DLT is defined as any of the toxicities described in the protocol occurring within the DLT assessment unless the event can clearly be determined to be unrelated to CC-90011

  Up to approximately 2 years

• Maximum Tolerated Dose (MTD)

  MTD is the highest dose that causes DLTs in not more than 33% of the subjects treated with CC-90010 in the first cycle with at least 6 evaluable subjects treated at this dose

  Up to approximately 2 years

• Adverse Events (AEs)

  An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE

  Up to approximately 3 years

Secondary Outcomes (9)

• Objective Response Rate (ORR)

  Up to approximately 2 years

• Progression-free Survival (PFS)

  Up to approximately 2 years

• Overall Survival (OS)

  Up to approximately 2 years

• Pharmacokinetics- Cmax

  Up to approximately 2 years

• Pharmacokinetics- AUC

  Up to approximately 2 years

Study Arms (3)

CC-90011 in combination with Cisplatin and Etoposide

EXPERIMENTAL

During the Chemotherapy Treatment Period, the dose escalation is designed to explore three dose levels of CC-90011, for example 20, 40, and 60 mg as determined by Bayesian design, administered orally Days 1 and 8, in combination with cisplatin intravenous (IV) 75 mg/m2, Day 1, and etoposide iv 100 mg/m2 on Days 1, 2, and 3, for 4 cycles of 21 days each. Subjects completing the chemotherapy and being responders as per RECIST 1.1 will enter the Maintenance Treatment Period. Subjects completing 6 cycles of maintenance treatment subject will be treated only with CC-90011 at RP2D (60 mg) and continuing on CC-90011 are only required to have clinic visits/assessments performed on Day 1 (± 3 days) of each subsequent cycle (Cycles 6 and higher) unless more frequent visits are clinically indicated.

Drug: CC-90011; Drug: Cisplatin

CC-90011 in combination with Carboplatin and Etoposide

EXPERIMENTAL

During the Chemotherapy Treatment Period, the dose escalation is designed to explore three dose levels of CC-90011, for example 20, 40, and 60 mg as determined by Bayesian design, administered orally Days 1 and 8, in combination with cisplatin intravenous (IV) 75 mg/m2, Day 1, and etoposide iv 100 mg/m2 on Days 1, 2, and 3, for 4 cycles of 21 days each. Subjects completing the chemotherapy and being responders as per RECIST 1.1 will enter the Maintenance Treatment Period. Subjects completing 6 cycles of maintenance treatment subject will be treated only with CC-90011 at RP2D (60 mg) and continuing on CC-90011 are only required to have clinic visits/assessments performed on Day 1 (± 3 days) of each subsequent cycle (Cycles 6 and higher) unless more frequent visits are clinically indicated

Drug: Carboplatin; Drug: Etoposide

Nivolumab combination

EXPERIMENTAL

When the RP2D of CC-90011 in combination with cisplatin or carboplatin and etoposide is determined, the combination of CC-90011 at RP2D with cisplatin or carboplatin and etoposide plus nivolumab IV 240 mg Day 1 of each chemotherapy cycle, will be explored. For CC-90011 in combination with chemotherapy and nivolumab, the starting dose will be the RP2D of CC-90011 in combination with chemotherapy. A maintenance therapy will be given to subjects responding to the combination of CC-90011 with chemotherapy or to chemotherapy with nivolumab, as per RECIST 1.1. These subjects will receive 60 mg or 40 mg (in case of combination with nivolumab) of CC-90011 orally once weekly on Days 1, 8, 15, and 22, during cycles of 28-day each and, in the case of the combination with nivolumab, nivolumab IV 480 mg on Day 1 during cycles of 28-day each.

Drug: Nivolumab

Interventions

CC-90011 DRUG

CC-90011

CC-90011 in combination with Cisplatin and Etoposide

Cisplatin DRUG

Cisplatin

CC-90011 in combination with Cisplatin and Etoposide

Carboplatin DRUG

Carboplatin

CC-90011 in combination with Carboplatin and Etoposide

Etoposide DRUG

Etoposide

CC-90011 in combination with Carboplatin and Etoposide

Nivolumab DRUG

Nivolumab

Nivolumab combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subject is 18 years of age or older at the time of signing the informed consent form (ICF).
• Subject with histological or cytological confirmation of extensive stage SCLC according to 2015 WHO classification (Travis, 2015).
• Subject must be able to provide fresh or archival tumor tissues
• Subject is found suitable for at least 4 cycles of platinum-based standard chemotherapy.
• Subject has at least 1 site of measurable disease per RECIST 1.1.
• Subject must have the following laboratory values:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Hemoglobin (Hgb) ≥ 10 g/dL (≥ 100 g/L or \> 6.2 mmol/L)
• Platelet count (Plt) ≥ 150 x 109/L
• Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamate pyruvate transaminase (ALT/SGPT) ≤ 3.0 x upper limit of normal (ULN) or ≤ 5.0 x ULN if liver metastases are present
• Serum total bilirubin ≤ 1.5 x ULN
• Serum creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 60 mL/min (see Appendix G to see creatinine clearance formula). For the purposes of this protocol, the glomerular filtration rate (GFR) is considered to be equivalent to the creatinine clearance.
• Prothrombin time (or international normalized ratio \[INR\]) and activated partial thromboplastin time (APTT) ≤ 1.5 ULN
• Females of childbearing potential (FCBP) must:
• Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use one highly effective contraceptive method plus one barrier method.

You may not qualify if:

• Subject has received anticancer therapy (either approved or investigational, including radiation with curative intent) for SCLC prior to study entry.
• Subject has undergone major surgery ≤ 4 weeks prior to Cycle 1 Day 1 or has not recovered from surgery.
• Subject has persistent diarrhea due to a malabsorptive syndrome (such as celiac sprue or inflammatory bowel disease) ≥ NCI CTCAE Grade 2, despite medical management), or any other significant gastrointestinal (GI) disorder that could affect the absorption of CC- 90011.
• Subject with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly those with a history of and/or risk of perforation and GI tract hemorrhages.
• Subject with any hemorrhage/bleeding event \> CTCAE Grade 2 or hemoptysis \> 1 teaspoon within 4 weeks prior to the first dose.
• Subject with symptomatic and untreated or unstable central nervous system (CNS) metastases.
• Subject has impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• \- Left ventricular ejection fraction (LVEF) \< 45% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO).
• \- Complete left bundle branch or bifascicular block.
• \- Congenital long QT syndrome.
• \- Persistent or clinically meaningful ventricular arrhythmias or atrial fibrillation.
• \- QTcF ≥ 480 msec on Screening ECG (mean of triplicate recordings).
• Subject has other clinically significant heart disease such as congestive heart failure requiring treatment or uncontrolled hypertension (blood pressure ≥ 160/95 mm Hg).
• Subject is a pregnant or nursing female.
• Subject has known human immunodeficiency virus (HIV) infection.

Sponsors & Collaborators

• Celgene: lead

Study Sites (13)

Local Institution - 102

Marseille, 13385, France

Location

Local Institution - 103

Saint-Herblain, 44800, France

Location

Local Institution - 100

Villejuif, 94805, France

Location

Local Institution - 203

Ancona, 60126, Italy

Location

Local Institution - 200

Bologna, 40138, Italy

Location

Local Institution - 201

Rozzano (MI), 20089, Italy

Location

Local Institution - 406

Majadahonda, Madrid, 28222, Spain

Location

Local Institution - 403

Barcelona, 08035, Spain

Location

Local Institution - 402

Barcelona, 08916, Spain

Location

Local Institution - 400

Madrid, 28041, Spain

Location

Local Institution - 404

Málaga, 29010, Spain

Location

Local Institution - 405

Valencia, 46010, Spain

Location

Local Institution - 401

Valencia, 46026, Spain

Location

Related Publications (1)

• Kanouni T, Severin C, Cho RW, Yuen NY, Xu J, Shi L, Lai C, Del Rosario JR, Stansfield RK, Lawton LN, Hosfield D, O'Connell S, Kreilein MM, Tavares-Greco P, Nie Z, Kaldor SW, Veal JM, Stafford JA, Chen YK. Discovery of CC-90011: A Potent and Selective Reversible Inhibitor of Lysine Specific Demethylase 1 (LSD1). J Med Chem. 2020 Dec 10;63(23):14522-14529. doi: 10.1021/acs.jmedchem.0c00978. Epub 2020 Oct 9.

  PMID: 33034194 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

pulrodemstat besilate; Cisplatin; Carboplatin; Etoposide; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

• Oscar Juan Vidal, MD, PhD

  Hospital Universitario La Fe

  PRINCIPAL INVESTIGATOR

• Stefania Salvagni, MD

  Azienda Ospedaliero Universitarua, Policlinico S. Orsola Malpighi

  PRINCIPAL INVESTIGATOR

• Rossana Berardi, MD

  Ospedali Riuniti di Ancona

  PRINCIPAL INVESTIGATOR

• Armando Santoro, MD

  IRCCS Instituto Clinic Humanitas

  PRINCIPAL INVESTIGATOR

• Benjamin Besse, MD, PhD

  Gustave Roussy, Ditep

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2019
• First Posted: February 21, 2019
• Study Start: March 12, 2019
• Primary Completion: July 16, 2024
• Study Completion: July 16, 2024
• Last Updated: August 26, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

IT (3); ES (7); FR (3)