A Dose Finding and Expansion Study of RO7051790 Administered Orally in Participants With Relapsed, Extensive-Stage Disease Small Cell Lung Cancer (ED SCLC)

Small Cell Lung Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02913443
• Other study ID #: NP39148
• Secondary ID: 2016-001942-25
• Status: Completed
• Phase: Phase 1
• Start date: December 20, 2016
• Est. completion date: October 24, 2017

Study information

• Verified date: October 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: October 24, 2017
• Est. primary completion date: October 24, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• RO7051790
RO7051790 will be given orally. Treatment will be continued until disease progression/treatment failure, unacceptable toxicity, or study discontinuation.

Locations

Country	Name	City	State
Canada	The Ottawa Hospital Cancer Centre; Oncology	Ottawa	Ontario
Canada	University Health Network; Princess Margaret Hospital; Medical Oncology Dept	Toronto	Ontario
Denmark	Rigshospitalet; Onkologisk Klinik	København Ø
France	Institut Gustave Roussy	Villejuif
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona
Spain	Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Adverse Events		Baseline up to approximately 18 weeks
Primary	Number of Participants with Dose-Limited Toxicities (DLTs)	DLTs were to be assessed based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. DLTs were at least possibly related to RO7051790 and had to meet any one of the following criteria: Grade=4 neutropenia lasting >7 days; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia with bleeding; Grade=4 anemia; Febrile neutropenia; Grade=3 elevation in serum hepatic transaminase lasting >7 days; Grade=3 elevation of serum bilirubin; and Grade=3 non-hematologic, non-hepatic adverse event (with few exceptions).	First treatment cycle (21 days)
Secondary	Percentage of Participants with Best Confirmed Overall Response	Best Confirmed Overall Response was evaluated according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Complete Response (CR) included the disappearance of all target lesions; Partial Response (PR) was at least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD) was at least a 20% increase in the sum of diameters of target lesions; and Stable Disease (SD) was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.	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)
Secondary	Percentage of Participants with Objective Response According to RECIST	Objective response was defined as the percentage of participants with a Complete Response (CR) or Partial Response (PR) as defined by the Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as the disappearance of all target lesions; PR was defined as a 30% decrease in sum of longest diameter of target lesions.	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)
Secondary	Duration of Response According to RECIST v1.1	Duration of response was defined as the interval between the date of the first documented response by RECIST to the date of first disease progression or death, whichever occurred earlier.	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)
Secondary	Progression-Free Survival (PFS) According to RECIST v1.1	Progression-free survival was defined as the time from the first administration of any study treatment to the first disease progression using RECIST or death from any cause, whichever occurred first.	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)
Secondary	Overall Survival (OS)		Time from first study treatment to death from any cause (up to approximately 12 months)
Secondary	Maximum Observed Plasma Concentration (Cmax) of RO7051790		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
Secondary	Minimum Observed Plasma Trough Concentration (Cmin) of RO7051790		Predose (0 hrs) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days)
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO7051790		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
Secondary	Plasma Decay Half-Life (t1/2) of RO7051790		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
Secondary	Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of RO7051790		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
Secondary	Area Under the Curve from Time Zero to End of Dosing Interval (AUCtau) of RO7051790		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
Secondary	Apparent Oral Clearance (CL/F) of RO7051790		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
Secondary	Apparent Volume of Distribution (Vz/F) of RO7051790		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
Secondary	Accumulation Ratio (RA) of RO7051790		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