A phase 1 study of oral Debio 0123 in combination with carboplatin in patients with advanced solid tumors.
- Conditions
- Advanced Malignancy / Cancer10027655
- Registration Number
- NL-OMON56391
- Lead Sponsor
- Debiopharm
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 81
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.
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 (< 55%)
5.Baseline Fridericia's corrected QT (QTcF) interval greater than 470 ms
(female) or greater than 450 ms (male), history of congenital long QT syndrome,
the presence in the screening ECG of a conduction abnormality that in the
opinion of the Investigator would preclude safe participation in this study.
6.Concomitant use of a drug with a known risk of QTc. If such a drug has been
used by the subject, a wash-out period of at least 5 half-lives of the drug
must occur before the first administration of study treatment.
7. Concomitant use of a drug or herbal product that is an inhibitor or inducer
of CYP3A4, orr concomitant use of any drug(s) on the prohibited medication list
(provided in Section 6.5.3). If such a drug has been used by the subject, a
wash-out period of at least 5 half-lives of the drug must occur before the
first administration of study treatment. For irreversible CYP inhibitors and
CYP inducers, a 4-week wash-out period must be applied.
8.Known infection requiring the systemic use of, for example, an antibiotic or
antiviral agent.
9.Pregnant or lactating woman with positive pregnancy test result
10.Chemotherapy, monoclonal antibodies/biologics, radiotherapy with curative
intent or coronavirus disease-19 (COVID-19) vaccine within 28 days prior to
starting study treatment. Treatment can start earlier if toxicities from
previous treatment(s) are reduced to grade 1, and the investigator judges that
treatment cannot wait. Palliative radiation for pain relief is allowed up to
one week prior to study treatment start.
11.Not recovered from AEs (>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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Dose escalation part: RP2D of Debio 0123 when administered in combination with<br /><br>carboplatin.<br /><br><br /><br>Expansion part: Safety and tolerability: Incidence of treatment-emergent SAEs,<br /><br>incidence and severity of TEAEs and laboratory abnormalities graded according<br /><br>to NCI-CTCAE version 5.0 criteria, incidence of treatment discontinuations and<br /><br>treatment modifications dut to AEs and laboratory abnormalities, change in<br /><br>vital signs, ECG, and ECOG PS. Preliminary anti-tumor activity: Tumor response<br /><br>according to RECIST version 1.1: ORR. </p><br>
- Secondary Outcome Measures
Name Time Method