Study of Oral Debio 0123 in Combination With Carboplatin in Participants With Advanced Solid Tumors

Advanced Solid Tumors Clinical Trial

Official title:

A Phase 1 Study of Oral Debio 0123 in Combination With Carboplatin in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03968653
• Other study ID #: Debio 0123-101
• Secondary ID: 2018-003659-39
• Status: Recruiting
• Phase: Phase 1
• Start date: July 30, 2019
• Est. completion date: April 2027

Study information

• Verified date: May 2024
• Source: Debiopharm International SA
• Contact: Debiopharm International S.A
• Phone: +41 21 321 01 11
• Email: clinicaltrials[@]debiopharm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 115
• Est. completion date: April 2027
• Est. primary completion date: June 5, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

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.
• Carboplatin
Carboplatin will be given as an IV infusion in combination with Debio 0123 on Day 1 from Cycle 2 onwards in Group A.
• Debio 0123
Debio 0123 will be given as an oral capsule for 3 or 6 days during each 21-day cycle.
• Carboplatin
Carboplatin will be given as an IV infusion in combination with Debio 0123 on Day 1 from Cycle 1 onwards.

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Leiden University Medical Center, Dept. of Clinical Oncology	Leiden
Netherlands	Radboud university medical center	Nijmegen
Spain	Hospital Vall Hebrón, Unidad de Investigación en Terapia Molecular (UITM)	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Debiopharm International SA

Countries where clinical trial is conducted

Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Escalation: 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)
Primary	Dose Expansion: Percentage of Participants with Treatment-Emergent Serious Adverse Events (SAEs)		Up to 46 months
Primary	Dose Expansion: Percentage of Participants with Treatment Discontinuations and Treatment Modifications Due to Adverse Events (AEs) and Laboratory Abnormalities		Up to 46 months
Primary	Dose Expansion: Overall Response Rate (ORR)		From the start of study treatment until disease progression/recurrence is documented or analysis cut-off, whichever occurs first (up to 46 months)
Secondary	Dose Escalation: 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)
Secondary	Dose Escalation: Percentage of Participants with Treatment-Emergent SAEs		Up to 46 months
Secondary	Dose Escalation: Percentage of Participants with TEAEs and Laboratory Abnormalities		Up to 46 months
Secondary	Dose Escalation: Percentage of Participants with Treatment Discontinuations and Treatment Modifications Due to Adverse Events (AEs) and Laboratory Abnormalities		Up to 46 months
Secondary	Dose Escalation: 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]
Secondary	Dose Escalation: Number of Participants with Changes in ECG		Up to 46 months
Secondary	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]
Secondary	Dose Escalation: Group A: Plasma Concentration of Debio 0123	The pharmacokinetics (PK) of Debio 0123 will be evaluated in plasma.	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)
Secondary	Dose Escalation: Group A: Concentration of Debio 0123 in Urine	The PK of Debio 0123 will be evaluated in urine.	Day -3 to Day 21 Cycle 1 (Cycle 1 = 24 days)
Secondary	Dose Escalation: Group A: Area Under the Concentration Curve Over the Time 0 to Infinity (AUC8) 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)
Secondary	Dose Escalation: Group B: Plasma Concentration of Debio 0123	The PK of Debio 0123 will be evaluated in plasma.	Cycle 1 to Cycle 3: Days 1 and 10 (cycle length = 21 days)
Secondary	Dose Escalation: Group B: Concentration of Free Platinum in Plasma of Carboplatin		Cycle 1 Day 1 (cycle length = 21 days)
Secondary	Dose Escalation: Correlation Between Plasma Concentration of Debio 0123 and Changes in QT Interval Corrected Using Fridericia's Formula (QTcF)		Up to 46 months
Secondary	Dose Escalation: 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)
Secondary	Dose Escalation: 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)
Secondary	Dose Escalation: Overall Survival (OS)		From the start of study treatment until death from any cause (Up to 46 months)
Secondary	Dose Expansion: Best Overall Response (BOR)		From the start of study treatment until disease progression/recurrence is documented or analysis cut-off, whichever occurs first (Up to 46 months)
Secondary	Dose Expansion: Disease Control Rate		From the start of study treatment until disease progression/recurrence is documented or analysis cut-off, whichever occurs first (Up to 46 months)
Secondary	Dose Expansion: Number of Participants with Best Change in Tumor Size		From the start of study treatment until disease progression/recurrence is documented or analysis cut-off, whichever occurs first (Up to 46 months)
Secondary	Dose Expansion: Duration of Response (DOR)		Up to disease progression (Up to 46 months)
Secondary	Dose Expansion: Time to Progression (TTP)		Time from treatment initiation until objective tumor progression (Up to 46 months)
Secondary	Dose Expansion: Plasma Concentration of Debio 0123		Cycle 1 and Cycle 2: Days 1, 3, 8 and 15 (cycle length = 21 days)