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

NCT02913443 | Completed Phase 1

• 2 other identifiers: NP391482016-001942-25
• Study Type: interventional
• Target: 18
• Locations: 5 countries
• Sites: 8

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.

Conditions

Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants with Adverse Events

  Baseline up to approximately 18 weeks

• 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 Outcomes (14)

• Percentage of Participants with Best Confirmed Overall Response

  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)

• Percentage of Participants with Objective Response According to RECIST

  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)

• Duration of Response According to RECIST v1.1

  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)

• Progression-Free Survival (PFS) According to RECIST v1.1

  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)

• Overall Survival (OS)

  Time from first study treatment to death from any cause (up to approximately 12 months)

Study Arms (4)

Introductory Cohort - 400 μg RO7051790

EXPERIMENTAL

Introductory cohort to ensure participant safety, prior to the dose escalation study. 400 μg of RO7051790 was administered to two (2) participants followed by a 21-day DLT observation period.

Drug: RO7051790

Dose Escalation - 1000 μg RO7051790

EXPERIMENTAL

1000 μg of RO7051790 was administered to six (6) participants once every 3 weeks (Q3W).

Drug: RO7051790

Dose Escalation - 1300 μg RO7051790

EXPERIMENTAL

1300 μg of RO7051790 was administered to seven (7) participants once every 3 weeks (Q3W).

Drug: RO7051790

Dose Escalation - 1900 μg RO7051790

EXPERIMENTAL

1900 μg of RO7051790 was administered to three (3) participants once every 3 weeks (Q3W).

Drug: RO7051790

Interventions

RO7051790 DRUG

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

Dose Escalation - 1000 μg RO7051790; Dose Escalation - 1300 μg RO7051790; Dose Escalation - 1900 μg RO7051790; Introductory Cohort - 400 μg RO7051790

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (8)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

The Ottawa Hospital Cancer Centre; Oncology

Ottawa, Ontario, K1H 8L6, Canada

Location

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

Toronto, Ontario, M5G 2M9, Canada

Location

Rigshospitalet; Onkologisk Klinik

København Ø, 2100, Denmark

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, 08035, Spain

Location

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, 28041, Spain

Location

Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica

Madrid, 28050, Spain

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Condition Hierarchy (Ancestors)

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

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: September 16, 2016
• First Posted: September 23, 2016
• Study Start: December 20, 2016
• Primary Completion: October 24, 2017
• Study Completion: October 24, 2017
• Last Updated: October 19, 2018

Record last verified: 2018-10

Locations

ES (3); US (1); DK (1); CA (2); FR (1)