Clinical trial NCT03968653: Study of Oral Debio 0123 in Combination With Carboplatin in Participants With Advanced Solid Tumors
Official title: A Phase 1 Study of Oral Debio 0123 in Combination With Carboplatin in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: WEE1-inhibitor
Lead sponsor: Debiopharm International SA
Sponsor class: INDUSTRY
First posted: 2019-05-30
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study has two parts: Dose Escalation and Dose Expansion. The primary objective of the study, in the Dose Escalation Part 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.

The primary objective of the study, in the Dose Expansion Part is to characterize the safety and tolerability of Debio 0123 when administered in combination with carboplatin at the RP2D determined during the dose escalation part of the study and to evaluate the preliminary antitumor activity of Debio 0123 when administered in combination with carboplatin.


Eligibility criteria: Inclusion Criteria:

Dose Escalation:

* 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
* Able and willing to undergo tumor biopsy
* Prior platinum-based therapy (carboplatin or cisplatin).
* Life expectancy of at least 3 months
* ECOG PS 0-1

Dose Expansion:

* Histologically or cytologically confirmed, recurrent solid tumors of selected types.
* Participants must have progressed after at least 1 prior platinum-based line of therapy for advanced/metastatic disease.
* Participants must be platinum resistant (defined as progression within 6 months of completion of their most recent platinum-based chemotherapy). Prior poly (ADP-ribose) polymerase (PARP) inhibitor therapy is allowed. Platinum-based therapy does not need to be the last treatment prior to study entry.
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
* Documented progressive or recurrent disease according to RECIST 1.1 since the last anti-cancer therapy and prior to study entry
* Able and willing to undergo tumor biopsy
* ECOG PS 0-1
* Life expectancy of at least 3 months

Exclusion Criteria:

Dose Escalation and Dose Expansion:

* History of other malignancies requiring active treatment in the last 6 months
* Brain tumors and/or symptomatic brain metastases
* Receiving other investigating agents
* Presence of significant cardiovascular disease or other co-morbidities such as symptomatic ascites
* Prior exposure to any WEE1 inhibitor

Primary outcomes:
measure: Dose Escalation: Recommended Phase 2 Dose (RP2D) of Debio 0123 When Administered in Combination with Carboplatin
timeFrame: 2 Cycles i.e., 45 days (Cycle 1 = 24 days; Cycle 2 onwards = 21 day-cycles)
measure: Dose Expansion: Percentage of Participants with Treatment-Emergent Serious Adverse Events (SAEs)
timeFrame: Up to 46 months
measure: Dose Expansion: Percentage of Participants with Treatment Discontinuations and Treatment Modifications Due to Adverse Events (AEs) and Laboratory Abnormalities
timeFrame: Up to 46 months
measure: Dose Expansion: Overall Response Rate (ORR)
timeFrame: From the start of study treatment until disease progression/recurrence is documented or analysis cut-off, whichever occurs first (up to 46 months)
Secondary outcomes:
measure: Dose Escalation: Percentage of Participants with Dose Limiting Toxicities (DLTs) of Debio 0123 When Administered in Combination with Carboplatin
timeFrame: 2 Cycles i.e., 45 days (Cycle 1 = 24 days; Cycle 2 onwards = 21 day-cycles)
measure: Dose Escalation: Percentage of Participants with Treatment-Emergent SAEs
timeFrame: Up to 46 months
measure: Dose Escalation: Percentage of Participants with TEAEs and Laboratory Abnormalities
timeFrame: Up to 46 months
measure: Dose Escalation: Percentage of Participants with Treatment Discontinuations and Treatment Modifications Due to Adverse Events (AEs) and Laboratory Abnormalities
timeFrame: Up to 46 months
measure: Dose Escalation: Number of Participants with Changes in Vital Signs
timeFrame: 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]
measure: Dose Escalation: Number of Participants with Changes in ECG
timeFrame: Up to 46 months
measure: Number of Participants with Change in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
timeFrame: 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]
measure: Dose Escalation: Group A: Plasma Concentration of Debio 0123
timeFrame: 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)
measure: Dose Escalation: Group A: Concentration of Debio 0123 in Urine
timeFrame: Day -3 to Day 21 Cycle 1 (Cycle 1 = 24 days)
measure: Dose Escalation: Group A: Area Under the Concentration Curve Over the Time 0 to Infinity (AUC∞) of Free Platinum in Plasma Ultrafiltrate of Carboplatin in Combination
timeFrame: Day 1 to Day 21 Cycle 2 (Cycle 2 onwards = 21 day-cycles) and subsequent cycles (Up to 46 months)
measure: Dose Escalation: Group B: Plasma Concentration of Debio 0123
timeFrame: Cycle 1 to Cycle 3: Days 1 and 10 (cycle length = 21 days)
measure: Dose Escalation: Group B: Concentration of Free Platinum in Plasma of Carboplatin
timeFrame: Cycle 1 Day 1 (cycle length = 21 days)
measure: Dose Escalation: Correlation Between Plasma Concentration of Debio 0123 and Changes in QT Interval Corrected Using Fridericia's Formula (QTcF)
timeFrame: Up to 46 months
measure: Dose Escalation: Tumor Response
timeFrame: From the start of study treatment until disease progression/recurrence is documented or analysis cut-off, whichever occurs first (Up to 46 months)
measure: Dose Escalation: Progression Free-Survival (PFS)
timeFrame: From the start of study treatment until disease progression or death from any cause, whichever occurs first (Up to 46 months)
measure: Dose Escalation: Overall Survival (OS)
timeFrame: From the start of study treatment until death from any cause (Up to 46 months)
measure: Dose Expansion: Best Overall Response (BOR)
timeFrame: From the start of study treatment until disease progression/recurrence is documented or analysis cut-off, whichever occurs first (Up to 46 months)
measure: Dose Expansion: Disease Control Rate
timeFrame: From the start of study treatment until disease progression/recurrence is documented or analysis cut-off, whichever occurs first (Up to 46 months)
measure: Dose Expansion: Number of Participants with Best Change in Tumor Size
timeFrame: From the start of study treatment until disease progression/recurrence is documented or analysis cut-off, whichever occurs first (Up to 46 months)
measure: Dose Expansion: Duration of Response (DOR)
timeFrame: Up to disease progression (Up to 46 months)
measure: Dose Expansion: Time to Progression (TTP)
timeFrame: Time from treatment initiation until objective tumor progression (Up to 46 months)
measure: Dose Expansion: Plasma Concentration of Debio 0123
timeFrame: Cycle 1 and Cycle 2: Days 1, 3, 8 and 15 (cycle length = 21 days)
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leiden
country: Netherlands
facility: Leiden University Medical Center, Dept. of Clinical Oncology
city: Nijmegen
country: Netherlands
facility: Radboud university medical center
city: Barcelona
country: Spain
facility: Hospital Vall Hebrón, Unidad de Investigación en Terapia Molecular (UITM)
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
Study officials:
References: