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

Primary Purpose

Small Cell Lung Cancer

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
RO7051790
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham
  • The Ottawa Hospital Cancer Centre; Oncology
  • University Health Network; Princess Margaret Hospital; Medical Oncology Dept
  • Rigshospitalet; Onkologisk Klinik
  • Institut Gustave Roussy
  • Hospital Univ Vall d'Hebron; Servicio de Oncologia
  • Hospital Universitario 12 de Octubre; Servicio de Oncologia
  • Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Introductory Cohort - 400 μg RO7051790

Dose Escalation - 1000 μg RO7051790

Dose Escalation - 1300 μg RO7051790

Dose Escalation - 1900 μg RO7051790

Arm Description

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.

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

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

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

Outcomes

Primary Outcome Measures

Percentage of Participants with Adverse Events
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).

Secondary Outcome Measures

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.
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.
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.
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.
Overall Survival (OS)
Maximum Observed Plasma Concentration (Cmax) of RO7051790
Minimum Observed Plasma Trough Concentration (Cmin) of RO7051790
Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO7051790
Plasma Decay Half-Life (t1/2) of RO7051790
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of RO7051790
Area Under the Curve from Time Zero to End of Dosing Interval (AUCtau) of RO7051790
Apparent Oral Clearance (CL/F) of RO7051790
Apparent Volume of Distribution (Vz/F) of RO7051790
Accumulation Ratio (RA) of RO7051790

Full Information

First Posted
September 16, 2016
Last Updated
October 18, 2018
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT02913443
Brief Title
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

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
December 20, 2016 (Actual)
Primary Completion Date
October 24, 2017 (Actual)
Study Completion Date
October 24, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Introductory Cohort - 400 μg RO7051790
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose Escalation - 1000 μg RO7051790
Arm Type
Experimental
Arm Description
1000 μg of RO7051790 was administered to six (6) participants once every 3 weeks (Q3W).
Arm Title
Dose Escalation - 1300 μg RO7051790
Arm Type
Experimental
Arm Description
1300 μg of RO7051790 was administered to seven (7) participants once every 3 weeks (Q3W).
Arm Title
Dose Escalation - 1900 μg RO7051790
Arm Type
Experimental
Arm Description
1900 μg of RO7051790 was administered to three (3) participants once every 3 weeks (Q3W).
Intervention Type
Drug
Intervention Name(s)
RO7051790
Intervention Description
RO7051790 will be given orally. Treatment will be continued until disease progression/treatment failure, unacceptable toxicity, or study discontinuation.
Primary Outcome Measure Information:
Title
Percentage of Participants with Adverse Events
Time Frame
Baseline up to approximately 18 weeks
Title
Number of Participants with Dose-Limited Toxicities (DLTs)
Description
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).
Time Frame
First treatment cycle (21 days)
Secondary Outcome Measure Information:
Title
Percentage of Participants with Best Confirmed Overall Response
Description
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 Frame
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)
Title
Percentage of Participants with Objective Response According to RECIST
Description
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 Frame
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)
Title
Duration of Response According to RECIST v1.1
Description
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 Frame
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)
Title
Progression-Free Survival (PFS) According to RECIST v1.1
Description
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 Frame
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)
Title
Overall Survival (OS)
Time Frame
Time from first study treatment to death from any cause (up to approximately 12 months)
Title
Maximum Observed Plasma Concentration (Cmax) of RO7051790
Time Frame
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
Title
Minimum Observed Plasma Trough Concentration (Cmin) of RO7051790
Time Frame
Predose (0 hrs) on Day 1 of every cycle until end of treatment (up to 18 weeks, each cycle is 21 days)
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO7051790
Time Frame
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
Title
Plasma Decay Half-Life (t1/2) of RO7051790
Time Frame
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
Title
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of RO7051790
Time Frame
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
Title
Area Under the Curve from Time Zero to End of Dosing Interval (AUCtau) of RO7051790
Time Frame
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
Title
Apparent Oral Clearance (CL/F) of RO7051790
Time Frame
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
Title
Apparent Volume of Distribution (Vz/F) of RO7051790
Time Frame
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
Title
Accumulation Ratio (RA) of RO7051790
Time Frame
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
The Ottawa Hospital Cancer Centre; Oncology
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
University Health Network; Princess Margaret Hospital; Medical Oncology Dept
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Rigshospitalet; Onkologisk Klinik
City
København Ø
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
Hospital Univ Vall d'Hebron; Servicio de Oncologia
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre; Servicio de Oncologia
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica
City
Madrid
ZIP/Postal Code
28050
Country
Spain

12. IPD Sharing Statement

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

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