Clinical trial NCT02913443: A Dose Finding and Expansion Study of RO7051790 Administered Orally in Participants With Relapsed, Extensive-Stage Disease Small Cell Lung Cancer (ED SCLC)
Official title: A Multi-Center, Open Label, Phase I, Dose Finding and Expansion Study of RO7051790 Administered Orally in Patients With Relapsed, Extensive-Stage Disease Small Cell Lung Cancer (ED SCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Small Cell Lung Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-09-23
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a Phase I, open-label, multicenter study designed to assess the safety and tolerability of RO7051790 in participants with relapsed ED SCLC. This dose escalation and expansion study plans to determine the maximum tolerated dose and/or optimal biological dose as a recommended Phase 2 dose for RO7051790, based on the safety, tolerability, pharmacokinetic and pharmacodynamic profiles observed after oral administration of RO7051790.


Eligibility criteria: Inclusion Criteria:

* Life expectancy greater than or equal to (\>=) 12 weeks
* Participants must have histologically or cytologically confirmed diagnosis of SCLC
* Participants must have recurrent or refractory disease after receiving at least one prior platinum-containing chemotherapy regimen, or standard therapy is refused or not suitable. For participants in Canada: participants should also not be suitable for treatment with topotecan hydrochloride
* Acute toxicities from any prior treatment, surgery, or radiotherapy must be National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 Grade less than or equal to (\<=) 1
* Measureable disease per RECIST v1.1 prior to administration of study medication
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
* Adequate bone marrow function
* Adequate renal function
* Participant must be able to swallow and retain orally administered study treatment
* Women of childbearing potential and men should agree to use an effective form of contraception and to continue its use for the duration of study treatment and for a period of time after the last dose of study treatment

Exclusion Criteria:

* Active malignancy other than SCLC within the previous 5 years
* Participants who have received radiotherapy less than 2 weeks prior to first dose of study medication
* Surgical procedure or clinically significant trauma within 2 weeks of first dose of study treatment
* Treatment with any investigational agent \<=3 weeks prior to first dose of study treatment
* Participants with gastrectomy or pre-existing gastrointestinal disorders that may interfere with the proper absorption of the drug(s), as per conclusion of the clinical Investigator
* Participants medicated with anti-depressants reported to have lysine-specific histone demethylase 1A (KDM1A)/lysine (K)-specific demethylase 1A (LSD1) inhibitory activity (such as tranylcypromine or phenelzine) within 28 days of treatment start
* History of allergic reactions attributed to components of the formulated product(s)
* History of seizure disorders
* Participants with untreated central nervous system metastases, or history of previously treated disease. Participants must have stable hematological parameters, satisfying eligibility, platelet count must be stable for \>=2 weeks prior to study drug administration
* Participants who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
* Participants with evidence of electrolyte imbalance
* Participants who are pregnant or breastfeeding
* Participants who refuse to potentially receive blood products and/or have a hypersensitivity to blood products
* Participants with known bone marrow disorders which may interfere with bone marrow recovery or participants with delayed recovery from prior chemoradiotherapy
* Participants with known coagulopathy, platelet disorder or history of non-drug-induced thrombocytopenia
* Hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)-positive participants with active infection
* Use of strong Cytochrome P450 3A4 (CYP3A4) inducers while on study medication
* Participants with abnormal hepatic function
* Participants with history of clinically significant bleeding, specifically any history of intracranial hemorrhage/hemorrhagic cardiovascular accident (CVA), or participants with gastrointestinal bleeding within the 12 months prior to study entry
* Participants receiving therapeutic anti-coagulation or anti-platelet (anti-aggregant) therapies, except for therapeutic enoxaparin or low dose aspirin. Use of subcutaneous heparin prophylaxis, including low molecular weight heparin is also permitted

Primary outcomes:
measure: Percentage of Participants with Adverse Events
timeFrame: Baseline up to approximately 18 weeks
measure: Number of Participants with Dose-Limited Toxicities (DLTs)
timeFrame: First treatment cycle (21 days)
Secondary outcomes:
measure: Percentage of Participants with Best Confirmed Overall Response
timeFrame: Time from first study treatment to the time of progression or death from any cause, whichever occurs first (Assessed every 6 weeks up to approximately 18 weeks)
measure: Percentage of Participants with Objective Response According to RECIST
timeFrame: Time from first study treatment to the time of progression or death from any cause, whichever occurs first (assessed every 6 weeks up to approximately 18 weeks)
measure: Duration of Response According to RECIST v1.1
timeFrame: Time from first occurrence of a documented objective response to the time of progression or death from any cause, whichever occurs first (assessed every 6 weeks up to approximately 18 weeks)
measure: Progression-Free Survival (PFS) According to RECIST v1.1
timeFrame: Time from first study treatment to the time of progression or death from any cause, whichever occurs first (assessed every 6 weeks up to approximately 18 weeks)
measure: Overall Survival (OS)
timeFrame: Time from first study treatment to death from any cause (up to approximately 12 months)
measure: Maximum Observed Plasma Concentration (Cmax) of RO7051790
timeFrame: Predose (0 hours [hrs]) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days); Cycles 1 and 2: 1,2,4,6,8 (only in Cycle 1) hrs postdose on Day 1 and on Days 2 (only in Cycle 1), 4, 5 (only in Cycle 1), 8,12,15,19
measure: Minimum Observed Plasma Trough Concentration (Cmin) of RO7051790
timeFrame: Predose (0 hrs) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO7051790
timeFrame: Predose (0 hrs) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days); Cycles 1 and 2: 1, 2, 4, 6, 8 (only in Cycle 1) hrs postdose on Day 1 and on Days 2 (only in Cycle 1), 4, 5 (only in Cycle 1), 8, 12, 15, 19
measure: Plasma Decay Half-Life (t1/2) of RO7051790
timeFrame: Predose (0 hrs) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days); Cycles 1 and 2: 1, 2, 4, 6, 8 (only in Cycle 1) hrs postdose on Day 1 and on Days 2 (only in Cycle 1), 4, 5 (only in Cycle 1), 8, 12, 15, 19
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of RO7051790
timeFrame: Predose (0 hrs) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days); Cycles 1 and 2: 1, 2, 4, 6, 8 (only in Cycle 1) hrs postdose on Day 1 and on Days 2 (only in Cycle 1), 4, 5 (only in Cycle 1), 8, 12, 15, 19
measure: Area Under the Curve from Time Zero to End of Dosing Interval (AUCtau) of RO7051790
timeFrame: Predose (0 hrs) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days); Cycles 1 and 2: 1, 2, 4, 6, 8 (only in Cycle 1) hrs postdose on Day 1 and on Days 2 (only in Cycle 1), 4, 5 (only in Cycle 1), 8, 12, 15, 19
measure: Apparent Oral Clearance (CL/F) of RO7051790
timeFrame: Predose (0 hrs) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days); Cycles 1 and 2: 1, 2, 4, 6, 8 (only in Cycle 1) hrs postdose on Day 1 and on Days 2 (only in Cycle 1), 4, 5 (only in Cycle 1), 8, 12, 15, 19
measure: Apparent Volume of Distribution (Vz/F) of RO7051790
timeFrame: Predose (0 hrs) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days); Cycles 1 and 2: 1, 2, 4, 6, 8 (only in Cycle 1) hrs postdose on Day 1 and on Days 2 (only in Cycle 1), 4, 5 (only in Cycle 1), 8, 12, 15, 19
measure: Accumulation Ratio (RA) of RO7051790
timeFrame: Predose (0 hrs) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days); Cycles 1 and 2: 1, 2, 4, 6, 8 (only in Cycle 1) hrs postdose on Day 1 and on Days 2 (only in Cycle 1), 4, 5 (only in Cycle 1), 8, 12, 15, 19
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre; Oncology
state: Ontario
city: Toronto
country: Canada
facility: University Health Network; Princess Margaret Hospital; Medical Oncology Dept
state: Ontario
city: København Ø
country: Denmark
facility: Rigshospitalet; Onkologisk Klinik
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre; Servicio de Oncologia
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: