Advanced Malignancy / Cancer
Conditions
Interventions
Debio 0123 is formulated for oral administration in capsules of 20 mg, 30 mg,
60 mg, 100 mg, 130 mg and 150 mg strength (10 mg mini-tablets in hard gelatin
capsules)
Carboplatin: concentrate for sol
Sponsors
Debiopharm
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Dose escalation part: 1.Histologically or cytologically confirmed locally advanced or metastatic solid and non-bleeding 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. 2. In addition, for Arm B of the dose escalation part only: The subject should be willing to comply with the requirements for the food effect high gastric pH (lansoprazole) investigations and have no contraindications to these requirements. Expansion part: 1. Platinum-resistant, recurrent, histologically or cytologically confirm high grade (serious, clear cell, or endometrioid) EOC, primary peritoneal cancer, or fallopian tube cancer. 2. Measurable disease per RECIST version 1.1. 3. Documented progressive or recurrent disease according to RECIST version 1.1 since the last anti-cancer therapy and prior to study entry. Patients with CA-125 progression in the absence of measurable disease will NOT be eligible. Both dose escalation and Expansion: 1.Able and willing to undergo tumor biopsy unless archived tumor sample is available. 2.Previous platinum-based chemotherapy (carboplatin or cisplatin). 3.Life expectancy of at least 3 months in the best judgement of the Investigator. 4.Adequate bone marrow, liver biochemistry, renal function and adequate coagulation status 5.Female subjects of child-bearing potential must have a negative serum pregnancy test at screening and be willing to practice the following highly effective contraception methods from the time of study entry up to 6 months after the last day of treatment: Male subjects must agree to use a condom from study entry and up to 6 months after the last day of treatment. The subject's female partner should use highly effective contraception methods, which may include oral contraceptives or any of the methods outlined above, during this period.
Exclusion criteria
Exclusion criteria: 1.History of other malignancies requiring active treatment in the last 6 months. 2.Brain tumors and/or brain metastases unless they are asymptomatic, stable on recent imaging (not dated more than 30 days from the inclusion date) and have not required active treatment in the last 3 months. 3.History of myocardial infarction or stroke within 6 months, congestive heart failure greater than New York Heart Association (NYHA) class II, unstable angina pectoris, unexplained recurrent syncope, cardiac arrhythmia requiring treatment or family history of sudden death from cardiac-related causes before the age of 50, any cardiotoxicity experienced after previous chemotherapy. 4. Left ventricular ejection fraction (LVEF) below the normal range (grade 1) or toxicities due to previous treatments 12.Hypersensitivity to carboplatin or any of the excipients 13. Subjects who are exposed to high levels of ultraviolet (UV) light, for example occupational exposure to sunlight or sun bathing 14. Immunization with live or live-attenuated vaccine within 28 days prior to study inclusion or planned injection of live or live-attenuated vaccine. 15. For dose escalation Arm B only, hypersensitivity to lansoprazole or any of the excipients
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Dose escalation part: - Occurrence of DLTs - Incidence of treatment-emergent Serious Adverse Events (SAEs) - Incidence and severity of treatment-emergent adverse events (TEAEs) and laboratory abnormalities, graded according to NCI-CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 5.0 criteria - Incidence of treatment discontinuations and treatment modifications due to AEs and laboratory abnormalities - Change in vital signs, ECG, and ECOG PS (Eastern Cooperative Oncology Group performance status) - For Arm A, PK parameters of Debio 0123 in monotherapy in plasma and urine after single dose on Cycle Day -3 and following 3 days of dosing (i.e. after the morning dose on Cycle 1 Day 3) - For Arm A, PK parameters of Debio 0123 and carboplatin in combination after the morning dose of Debio 0123 on Cycle 2 Day 1. - For Arm B, PK parameters of Debio 0123 and its metabolite on Cycle 1 Day 1 and Cycle 1 Day 10, i.e. after the first and last dose of the first cycle - For Arm B, PK parameters of carboplatin (concentration of free platinum in plasma and other PK parameters as deemed appropriate) on Cycle 1 Day 1 - For Arm B, PK parameters of Debio 0123 and its metabolite on Day 10 of Cycle 2 (fed state) and Cycle 3 (high gastric pH with concomitant lansoprazole), compared to PK parameters on Day 10 of Cycle 1 (fasted state and normal gastric pH conditions) - Relationship between plasma concentration of Debio 0123 (and its metabolite) and changes in QTcF - Tumor response according to RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1 criteria: best overall response (BOR), overall response rate (ORR), disease control rate, best change in tumor size - Median and 1- and 2-years rates of progression-free survival (PFS) and OS Expansion part: - BOR, disease control rate, according to RECIST version 1.1, and best change in tumor size - Duration of response (DOR), time to progression (TTP) - Median | — |
Primary
| Measure | Time frame |
|---|---|
| Dose escalation part: RP2D of Debio 0123 when administered in combination with carboplatin. Expansion part: Safety and tolerability: Incidence of treatment-emergent SAEs, incidence and severity of TEAEs and laboratory abnormalities graded according to NCI-CTCAE version 5.0 criteria, incidence of treatment discontinuations and treatment modifications dut to AEs and laboratory abnormalities, change in vital signs, ECG, and ECOG PS. Preliminary anti-tumor activity: Tumor response according to RECIST version 1.1: ORR. | — |
Countries
Netherlands
Outcome results
None listed