Clinical trial NCT02875223: A Safety and Efficacy Study of CC-90011 in Participants With Relapsed and/or Refractory Solid Tumors and Non-Hodgkin's Lymphomas
Official title: A Phase 1, Open-label, Dose Finding Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CC-90011 in Subjects With Relapsed and/or Refractory Solid Tumors and Non-Hodgkin's Lymphomas
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Lymphoma, Non-Hodgkin
Neoplasms
Keywords: Safety
CC-90011
Advanced unresectable solid Tumors
Low intermediate-grade lung neuroendocrine tumors (Typical and Atypical carcinoids)
Neuroendocrine prostate cancer (NEPC)
R/R Non-Hodgkin's Lymphomas
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2016-08-23
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study CC-90011-ST-001 is an open-label, Phase 1, dose escalation and expansion, First-In-Human (FIH) clinical study of CC-90011 in subjects with advanced unresectable solid tumors (enriched for grade 2 NENs, grade 2 NETs and NECs) and R/R NHL (MZL, including extranodal MZL \[EMZL\], splenic MZL \[SMZL\], nodal MZL \[NMZL\], and histologic transformation of MZL). The dose escalation part (Part A) of the study will explore escalating oral doses of CC-90011 to estimate the maximum tolerated dose (MTD) of CC-90011. The expansion part (Part B) will further evaluate the safety and efficacy of CC-90011 administered at or below the MTD in 3 selected expansion cohorts of approximately 10-20 evaluable subjects each, in order to further define the RP2D.


Eligibility criteria: Inclusion Criteria:

* Advanced or unresectable solid tumors including those who have progressed on (or not been able to tolerate due to medical comorbidities or unacceptable toxicity) standard anticancer therapy or for whom no other approved conventional therapy exists
* Eastern Cooperative Oncology Group Performance Status of 0 to 1

Exclusion Criteria:

* Prior autologous stem cell transplant ≤ 3 months before first dose or those who have not recovered
* Symptomatic or uncontrolled ulcers (gastric or duodenal), particularly those with a history of and/or risk of perforation and gastrointestinal tract hemorrhages
* Impaired cardiac function or clinically significant cardiac diseases
* Poor bone marrow reserve as assessed by Investigator

Refer to protocol defined exclusion criteria for parts C and D. Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Part A - Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (Each cycle is of 28 days)
measure: Part A - Maximum Tolerated Dose (MTDs)
timeFrame: Cycle 1 (Each cycle is of 28 days)
Secondary outcomes:
measure: Part A - Clinical Benefit Rate (CBR) as Per Confirmed Best Overall Response Based on Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST 1.1)
timeFrame: From first dose (Day 1) till disease progression or death due to any cause (up to 803 days)
measure: Part A - Objective Response Rate as Per Confirmed Best Overall Response Based on Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST 1.1)
timeFrame: From first dose (Day 1) untill disease progression or death due to any cause (up to 803 days)
measure: Part A - Duration of Response (DoR) Based on Confirmed Responses
timeFrame: From first dose (Day 1) until disease progression or death due to any cause (up to 803 days)
measure: Part A - Progression-Free Survival (PFS)
timeFrame: From first dose (Day 1) until disease progression or death due to any cause (up to 803 days)
measure: Part A - Overall Survival (OS)
timeFrame: From first dose (Day 1) until death due to any cause (up to 803 days)
measure: Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011
timeFrame: Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days)
measure: Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011
timeFrame: Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days)
measure: Part A - Time to Cmax (Tmax) of CC-90011
timeFrame: Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days)
measure: Part A - Half-life (t1/2) of CC-90011
timeFrame: Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days)
measure: Part A - Apparent Clearance (CL/F) of CC-90011
timeFrame: Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days)
measure: Part A- Volume of Distribution (Vz/F) of CC-90011
timeFrame: Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days)
measure: Part B - Clinical Benefit Rate (CBR) as Per Confirmed Best Overall Response Based on Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST 1.1)
timeFrame: From first dose (Day 1) until disease progression or death due to any cause (up to 720 days)
measure: Part B - Objective Response Rate as Per Confirmed Best Overall Response Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST 1.1)
timeFrame: From first dose (Day 1) till disease progression or death due to any cause (up to 720 days)
measure: Part B - Duration of Response (DoR)
timeFrame: From first dose (Day 1) until disease progression or death due to any cause (up to 720 days)
measure: Part B - Progression Free Survival (PFS)
timeFrame: From first dose (Day 1) until disease progression or death due to any cause (up to 720 days)
measure: Part B - Overall Survival (OS)
timeFrame: From first dose (Day 1) until death due to any cause (up to 720 days)
Other outcomes:
Locations:
city: Dijon
country: France
facility: Local Institution - 101
city: Marseille Cedex 9
country: France
facility: Local Institution - 102
city: Villejuif Cedex
country: France
facility: Local Institution - 100
city: Bologna
country: Italy
facility: Local Institution - 200
city: Milano
country: Italy
facility: Local Institution - 201
city: Milano
country: Italy
facility: Local Institution - 202
city: Chuo-ku
country: Japan
facility: Local Institution - 501
state: Tokyo
city: Koto-Ku
country: Japan
facility: Local Institution - 502
state: Tokyo
city: Kashiwa
country: Japan
facility: Local Institution - 500
city: Barcelona
country: Spain
facility: Local Institution - 400
city: Madrid
country: Spain
facility: Local Institution - 402
city: Madrid
country: Spain
facility: Local Institution - 404
city: Santander
country: Spain
facility: Local Institution - 401
city: London
country: United Kingdom
facility: Local Institution - 300
city: Newcastle Upon Tyne
country: United Kingdom
facility: Local Institution - 301
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Hollebecque A, Salvagni S, Plummer R, Isambert N, Niccoli P, Capdevila J, Curigliano G, Moreno V, Martin-Romano P, Baudin E, Arias M, Mora S, de Alvaro J, Di Martino J, Parra-Palau JL, Sanchez-Perez T, Aronchik I, Filvaroff EH, Lamba M, Nikolova Z, de Bono JS. Phase I Study of Lysine-Specific Demethylase 1 Inhibitor, CC-90011, in Patients with Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin Lymphoma. Clin Cancer Res. 2021 Jan 15;27(2):438-446. doi: 10.1158/1078-0432.CCR-20-2380. Epub 2020 Oct 12.
citation: Hollebecque A, Salvagni S, Plummer R, Niccoli P, Capdevila J, Curigliano G, Moreno V, de Braud F, de Villambrosia SG, Martin-Romano P, Baudin E, Arias M, de Alvaro J, Parra-Palau JL, Sanchez-Perez T, Aronchik I, Filvaroff EH, Lamba M, Nikolova Z, de Bono JS. Clinical activity of CC-90011, an oral, potent, and reversible LSD1 inhibitor, in advanced malignancies. Cancer. 2022 Sep 1;128(17):3185-3195. doi: 10.1002/cncr.34366. Epub 2022 Jun 23.