A Phase 1 Dose-Escalation and Expansion Study to Assess Safety and Preliminary Antitumor Activity of Debio 0123 in Combination With Carboplatin and Etoposide in Adult Participants With Small Cell Lung Cancer That Recurred or Progressed After Previous Standard Platinum-Based Therapy
Overview
- Phase
- Phase 1
- Intervention
- Debio 0123
- Conditions
- Small Cell Lung Cancer Recurrent
- Sponsor
- Debiopharm International SA
- Enrollment
- 34
- Locations
- 24
- Primary Endpoint
- Part 1: Number of Participants Experiencing Dose-limiting Toxicities (DLTs)
- Status
- Active, not recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
The primary purpose of part 1 (dose escalation) of this study is to identify the recommended dose and to characterize the safety and tolerability of Debio 0123 in combination with carboplatin and etoposide.
The primary purpose of part 2 (dose expansion) of this study is to characterize the safety and tolerability of Debio 0123 at the recommended dose when administered in combination with carboplatin and etoposide.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed SCLC
- •Tumor that is not bleeding
- •Prior platinum-based chemotherapy (carboplatin and/or cisplatin)
- •Part 1 (dose escalation): Recurrence or progression after a minimum of 45 days since the last dose of prior standard platinum-based therapy
- •Part 2 (expansion): Recurrence or progression after a minimum of 90 days since the last dose of prior standard platinum-based therapy
- •Measurable disease per RECIST 1.1
- •Willingness and ability to undergo tumor biopsy unless an archived tumor sample is available
- •ECOG performance status of 0-1
- •Life expectancy of at least 3 months in the best judgment of the Investigator
- •Adequate bone marrow, hepatic and renal function, adequate coagulation status
Exclusion Criteria
- •Use of an investigational agent or medical device within 28 days prior to first dose of study treatment.
- •History of other malignancies requiring active treatment in the last 2 years prior to first dose of study treatment, except for superficial bladder cancers, ductal carcinoma in situ or other carcinomas in situ, and non-melanoma skin cancers (basal cell/squamous cell skin cancer) that have been treated with curative intent.
- •History of myocardial infarction or stroke in the last 6 months prior to first dose of study treatment, congestive heart failure greater than New York Heart Association (NYHA) class II, unstable angina pectoris, unexplained recurrent syncope, cardiac arrhythmia requiring treatment, known family history of sudden death from cardiac-related causes before the age of 50, or any cardiotoxicity experienced after previous chemotherapy.
- •Left ventricular ejection fraction (LVEF) below 55%.
- •QTcF \>450 ms, history of congenital long QT syndrome, or clinically significant conduction abnormality, or any conduction abnormality that may increase the risk of TdP.
- •Clinically significant gastrointestinal abnormality that could affect the absorption of orally administered drugs
- •Major surgery ≤4 weeks prior to first dose of study treatment or incomplete recovery from the surgical procedure at the time of the first dose of study treatment.
- •Radiographic findings showing tumor involvement with large blood vessels or poor demarcation from them with increased risk for bleeding.
- •Radiographic findings of Interstitial lung disease (ILD) that are considered clinically significant.
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
Arms & Interventions
Part 1: Dose Escalation: Debio 0123 + Etoposide + Carboplatin
Participants will receive Debio 0123 escalating doses, orally along with etoposide IV infusion and carboplatin IV infusion in 21-day cycles until disease progression or death or end of study.
Intervention: Debio 0123
Part 1: Dose Escalation: Debio 0123 + Etoposide + Carboplatin
Participants will receive Debio 0123 escalating doses, orally along with etoposide IV infusion and carboplatin IV infusion in 21-day cycles until disease progression or death or end of study.
Intervention: Etoposide
Part 1: Dose Escalation: Debio 0123 + Etoposide + Carboplatin
Participants will receive Debio 0123 escalating doses, orally along with etoposide IV infusion and carboplatin IV infusion in 21-day cycles until disease progression or death or end of study.
Intervention: Carboplatin
Part 2: Dose Expansion: Debio 0123 + Etoposide + Carboplatin
Participants will receive Debio 0123 recommended dose determined in Part 1 of the study, orally along with etoposide IV infusion and carboplatin IV infusion in 21-day cycles until disease progression or death or end of study.
Intervention: Debio 0123
Part 2: Dose Expansion: Debio 0123 + Etoposide + Carboplatin
Participants will receive Debio 0123 recommended dose determined in Part 1 of the study, orally along with etoposide IV infusion and carboplatin IV infusion in 21-day cycles until disease progression or death or end of study.
Intervention: Etoposide
Part 2: Dose Expansion: Debio 0123 + Etoposide + Carboplatin
Participants will receive Debio 0123 recommended dose determined in Part 1 of the study, orally along with etoposide IV infusion and carboplatin IV infusion in 21-day cycles until disease progression or death or end of study.
Intervention: Carboplatin
Outcomes
Primary Outcomes
Part 1: Number of Participants Experiencing Dose-limiting Toxicities (DLTs)
Time Frame: Cycle 1 (Cycle=21 days)
Parts 1 and 2: Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE)
Time Frame: Approximately up to 44 months
Parts 1 and 2: Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Time Frame: Baseline up to approximately 44 months
Parts 1 and 2: Number of Participants With Clinically Significant Abnormalities in Laboratory, Vital Signs, Electrocardiogram (ECG), and Echocardiogram Parameters
Time Frame: Approximately up to 44 months
Secondary Outcomes
- Part 1: Area Under the Concentration Curve up to Infinity (AUCinf) of Debio 0123 and its Metabolite(Multiple timepoints post dose from Day 1 to Day 21 of Cycle 1 and Day 1 of Cycle 2 (Cycle=21 days))
- Part 1: Apparent Terminal Half-life (t1/2) of Debio 0123 and its Metabolite(Multiple timepoints post dose from Day 1 to Day 21 of Cycle 1 and Day 1 of Cycle 2 (Cycle=21 days))
- Part 1: Apparent Clearance (CL/F) of Debio 0123(Multiple timepoints post dose from Day 1 to Day 21 of Cycle 1 and Day 1 of Cycle 2 (Cycle=21 days))
- Part 1: Apparent Volume of Distribution (Vd/F) of Debio 0123(Multiple timepoints post dose from Day 1 to Day 21 of Cycle 1 and Day 1 of Cycle 2 (Cycle=21 days))
- Part 1: Maximum Plasma Concentration (Cmax) of Etoposide(Multiple timepoints from administration to post dose from Day 1 to Day 3 of Cycle 1 (Cycle=21 days)])
- Part 1: Area Under the Concentration Curve Over 24 hours (AUC24h) of Etoposide(Multiple timepoints post dose from Day 1 to Day 5 of Cycle 1 (Cycle=21 days))
- Part 1: Trough Concentration (Ctrough) of Etoposide(Predose from Day 2 to Day 5 of Cycle 1 (Cycle=21 days))
- Part 1: Maximum Plasma Concentration (Cmax) of Carboplatin(Multiple timepoints from administration up to 6 hours post dose on Day 1 of Cycle 1 (Cycle=21 days))
- Parts 1 and 2: Percentage of Participants With Best Overall Response (BOR) Assessed as per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 Criteria(From the start of study treatment until disease progression or end of study (up to approximately 44 months))
- Parts 1 and 2: Percentage of Participants With Objective Response (OR) Assessed as per RECIST 1.1 Criteria(Up to end of study (approximately 44 months))
- Parts 1 and 2: Percentage of Participants With Disease Control (DC) Assessed as per RECIST 1.1 Criteria(From the start of study treatment until disease progression or end of study (up to approximately 44 months))
- Parts 1 and 2: Duration of Response (DOR) Assessed as per RECIST 1.1 Criteria(Up to disease progression or end of study (approximately 44 months))
- Parts 1 and 2: Progression Free Survival (PFS) Assessed as per RECIST 1.1 Criteria(From the start of study treatment until disease progression or death or end of study (up to approximately 44 months))
- Parts 1 and 2: Trough Concentration (Ctrough) of Debio 0123 and its Metabolite(For Part 1: Predose from Day 2 to Day 11 of Cycle 1; For Part 2: Predose from Day 3 to Day 10 of Cycle 1 and only Day 8 of subsequent cycles up to Cycle 5 (Cycle=21 days))
- Parts 1 and 2: Maximum Plasma Concentration (Cmax) of Debio 0123 and its Metabolite(For Part 1: Multiple timepoints post dose from Day 1 to Day 11 of Cycle 1 (Cycle=21 days); For Part 2: Will be derived from the population Pharmacokinetic (PK) model using the sparse samples collected)
- Parts 1 and 2: Area Under the Concentration Curve Over 24 hours (AUC24h) of Debio 0123 and its Metabolite(For Part 1: Multiple timepoints post dose from Day 1 to Day 11 of Cycle 1 (Cycle=21 days); For Part 2: Will be derived from the population PK model using the sparse samples collected)
- Part 1: Time to Maximum Plasma Concentration (tmax) of Debio 0123 and its Metabolite(Multiple timepoints post dose from Day 1 to Day 11 of Cycle 1 (Cycle=21 days))
- Part 1: Area Under the Concentration Curve up to the Last Measurable Concentration (AUClast) of Debio 0123 and its Metabolite(Multiple timepoints post dose from Day 1 to Day 21 of Cycle 1 and Day 1 of Cycle 2 (Cycle=21 days))
- Part 2: Overall Survival(From the start of study treatment until death from any cause or end of study (up to approximately 44 months)