Phase 1/2 Clinical Trial of CP-506 (HAP) in Monotherapy or With Carboplatin or ICI
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorMaastricht University Medical Center
About this trial
A modular, first time in human, open label, multiple dose, accelerated escalation with cohort expansion study of the safety and pharmacokinetics of intravenous infusion of CP-506, a tumor agnostic Hypoxia Activated Prodrug in patients with HRD/FAD solid tumours or tumor types with high incidence of HRD/FAD in monotherapy or in combination with carboplatin or patients with solid tumour and oligoprogressive disease receiving immune checkpoint inhibitors (ICI): a phase I-IIa clinical trial
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Male or female, aged 18 years or more at the time of signing the informed consent
Be willing and able to provide written informed consent for the trial
Life expectancy of at least 3 months
Be willing to have a biopsy collection procedure
Disqualifiers
Prior radiotherapy to more than 25% of bone marrow
Not recovered from all acute toxic effects of prior anticancer therapy (excluding CTCAE Grade 1 alopecia or peripheral neuropathy)
Patients with significant cardiac co-morbidity, such as NYHA Class III or IV CHF, unstable angina, MI within the previous 6 months, or ventricular arrhythmias requiring drug therapy, pacemaker or implanted defibrillator. Serious, uncontrolled cardiac arrhythmia or clinically significant electrocardiogram abnormalities including second degree (Type II) or third-degree atrioventricular block. This does not apply to patient with a pace maker. Cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting or bypass grafting. Congestive heart failure (Class II, III, or IV) as defined by the New York Heart Association functional classification system. Symptomatic pericarditis
A marked baseline prolongation of QT/QTc interval (> 450 ms)
Trial design
Design model
Sequential
Treatments tested in this trial
CP-506
DrugCP-506 is a hypoxia-activated DNA alkylating agent specifically designed to have a bystander effect, aqueous solubility, oral bioavailability, and no off-mechanism activation by the human aerobic reductase AKR1C3
Carboplatin
DrugAntineoplastic agent, ATC Code: LO1X A02
Immune checkpoint inhibitor
DrugDrug that blocks immune checkpoint proteins: PD-1, PD-L1, CTLA-4
Treatment groups
126 Participants
are divided into 6 treatment groups6
Treatment groupsSee each treatment group below.
Group A: Module 1A Monotherapy Multiple Ascending DoseExperimental treatment 1 intervention
Group B: Module 1B Monotherapy Dose Expansion CohortExperimental treatment 1 intervention
Group C: Module 2A Combination with carboplatin Multiple Ascending DoseExperimental treatment 2 interventions
Group D: Module 2B Combination with carboplatin Dose Expansion CohortExperimental treatment 2 interventions
Group E: Module 3A Combination with Immune Checkpoint Inhibitor Multiple Ascending DoseExperimental treatment 2 interventions
Group F: Module 3B Combination with carboplatin Dose Expansion CohortExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Incidence of treatment-emergent adverse events including dose-limiting toxicities
The proportion of patients with treatment-emergent (serious) adverse events including dose-limiting toxicity (DLT)
Time frame
Baseline until 60 days after last administration of CP-5062
Incidence of clinically significant abnormal measurements in physical examination, vital signs, electrocardiogram (ECG), lab tests and ECOG performance status
Physical examination; vital signs; electrocardiogram (ECG); haematology; clinical chemistry; urinalysis; plasma/renal makers; tumour markers; ECOG performance status
Time frame
Baseline until 60 days after last administration of CP-506Secondary outcomes
1
Area under curve of CP-506 plasma concentration
Measurement of CP-506 levels in plasma over time to calculate AUC Area under the curve (AUC) of CP-506 plasma concentration
Time frame
At the end of cycle 1 day 42
Determine the minimal biological effective dose
Number of patients that show 1) a decrease of 20% of hypoxia radiomics score on sequential CT of at least one lesion OR 2) a decrease of 20% of the initial tumour volume of at least one lesion
Time frame
Baseline until 60 days after last administration of CP-5063
Objective Response Rate
Objective response rate (ORR) by RECIST 1.1 - the proportion of patients with a confirmed reduction in tumour burden of a predefined amount (this will include short lived responses).
Time frame
Baseline until 60 days after last administration of CP-5064
Percentage change in tumour size
Percentage change in tumour size will be determined for patients with measurable disease at baseline and is derived at each visit by the percentage change from baseline in the sum of the diameters of target lesions. The best percentage change in tumour size will be the patient's value representing the largest decrease (or smallest increase) from baseline in tumour size
Time frame
Baseline until 60 days after last administration of CP-506Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Maastricht University Medical Center
Lead sponsor
Erasmus Medical Center
Collaborator
Jules Bordet Institute
Collaborator
Academisch Ziekenhuis Maastricht
Collaborator
Vall d'Hebron Institute of Oncology
Collaborator
University Ghent
Collaborator
Source ClinicalTrials.gov