Study of Oral Debio 0123 in Combination With Carboplatin in Participants With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
The primary objective of the study is to determine the recommended phase 2 dose (RP2D) of Debio 0123 when administered in combination with carboplatin in participants with advanced solid tumors that recurred or progressed after prior cisplatin or carboplatin containing therapy and for which no standard therapy of proven benefit is available.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group A: Debio 0123 Participants will receive Debio 0123 as monotherapy (Day -3), orally, daily for 3 days during Cycle 1 then in combination with carboplatin intravenous infusion from Cycle 2 onwards. Depending on pharmacokinetics (PK) and safety results from previous cohorts, the Debio 0123 dosing regimen may be modified for subsequent cohorts. |
Drug: Debio 0123
Debio 0123 will be given as an oral capsule for 3 days during each 21-day cycle, except Cycle 1 which is of 24 days.
Drug: Carboplatin
Carboplatin will be given as an IV infusion in combination with Debio 0123 on Day 1 from Cycle 2 onwards in Group A.
|
| Experimental: Group B: Debio 0123 Participants will receive Debio 0123, orally, daily, for 6 days during each cycle in combination with carboplatin IV infusion. |
Drug: Debio 0123
Debio 0123 will be given as an oral capsule for 6 days during each 21-day cycle.
Drug: Carboplatin
Carboplatin will be given as an IV infusion in combination with Debio 0123 on Day 1 from Cycle 1 onwards.
|
Outcome Measures
Primary Outcome Measures
- Recommended Phase 2 Dose (RP2D) of Debio 0123 When Administered in Combination with Carboplatin [2 Cycles i.e., 45 days (Cycle 1 = 24 days; Cycle 2 onwards = 21 day-cycles)]
Secondary Outcome Measures
- Percentage of Participants with Dose Limiting Toxicities (DLTs) of Debio 0123 When Administered in Combination with Carboplatin [2 Cycles i.e., 45 days (Cycle 1 = 24 days; Cycle 2 onwards = 21 day-cycles)]
- Percentage of Participants with Treatment-Emergent Serious Adverse Events (SAEs) [Up to 46 months]
- Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs) and Laboratory Abnormalities [Up to 46 months]
- Percentage of Participants with Treatment Discontinuations and Treatment Modifications Due to Adverse Events (AEs) and Laboratory Abnormalities [Up to 46 months]
- Number of Participants with Changes in Vital Signs [Day 1 of each cycle (up to 46 months) [Group A: Cycle 1 = 24 days, Cycle 2 onwards and all cycles in Group B = 21-day cycles]]
- Number of Participants with Changes in Electrocardiogram (ECG) [Up to 46 months]
- Number of Participants with Change in Eastern Cooperative Oncology Group Performance Status (ECOG PS) [Day 1 of each cycle (up to 46 months) [Group A: Cycle 1 = 24 days, Cycle 2 onwards and all cycles in Group B = 21-day cycles]]
- Group A: Plasma Concentration of Debio 0123 [Day -3 to predose Day 1; postdose at multiple time points from Day 3 to Day 21 in Cycle 1 (Cycle 1 = 24 days), Day 1 on Cycle 2 (Cycle 2 onwards = 21 day-cycles) and subsequent cycles (Up to 46 months)]
The pharmacokinetics (PK) of Debio 0123 will be evaluated in plasma.
- Group A: Concentration of Debio 0123 in Urine [Day -3 to Day 21 Cycle 1 (Cycle 1 = 24 days)]
The PK of Debio 0123 will be evaluated in urine.
- Group A: Area Under the Concentration Curve Over the Time 0 to Infinity (AUC∞) of Free Platinum in Plasma Ultrafiltrate of Carboplatin in Combination [Day 1 to Day 21 Cycle 2 (Cycle 2 onwards = 21 day-cycles) and subsequent cycles (Up to 46 months)]
- Group B: Plasma Concentration of Debio 0123 [Cycle 1 to Cycle 3: Days 1 and 10 (cycle length = 21 days)]
The PK of Debio 0123 will be evaluated in plasma.
- Group B: Concentration of Free Platinum in Plasma of Carboplatin [Cycle 1 Day 1 (cycle length = 21 days)]
- Correlation Between Plasma Concentration of Debio 0123 and Changes in QT Interval Corrected Using Fridericia's Formula (QTcF) [Up to 46 months]
- Tumor Response [From the start of study treatment until disease progression/recurrence is documented or analysis cut-off, whichever occurs first (Up to 46 months)]
- Progression Free-Survival (PFS) [From the start of study treatment until disease progression or death from any cause, whichever occurs first (Up to 46 months)]
- Overall Survival (OS) [From the start of study treatment until death from any cause (Up to 46 months)]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically or cytologically confirmed locally advanced or metastatic solid and nonbleeding tumors that had recurred or progressed following standard therapy, has not responded to standard therapy or for which no standard therapy of proven benefit is available
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Able and willing to undergo tumor biopsy
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Prior platinum-based therapy (carboplatin or cisplatin).
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Life expectancy of at least 3 months
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ECOG performance score 0-1
Exclusion Criteria:
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History of other malignancies requiring active treatment in the last 6 months
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Brain tumors and/or symptomatic brain metastases
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Receiving other investigating agents
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Presence of significant cardiovascular disease or other co-morbidities such as symptomatic ascites
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Medical Center Groningen | Groningen | Netherlands | 9713 | |
| 2 | Leiden University Medical Center, Dept. of Clinical Oncology | Leiden | Netherlands | 2333 | |
| 3 | Radboud university medical center | Nijmegen | Netherlands | 6525 | |
| 4 | Hospital Vall Hebrón, Unidad de Investigación en Terapia Molecular (UITM) | Barcelona | Spain | 08035 |
Sponsors and Collaborators
- Debiopharm International SA
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Debio 0123-101
- 2018-003659-39