The purpose of this study is to determine the appropriate dosage, safety and effectiveness of the study drug, IPN01194 in adults with advanced solid tumours. The participants in this study will have advanced solid tumours. 'Advanced solid tumours' refers to cancers that can occur in several places, including cancers in organs or tissues that have spread from their original site to nearby tissues or other parts of the body. In this study, all participants will receive the study drug, which will be taken by mouth (orally).
The study consists of two parts, called Phase I and Phase IIa. Phase I is designed to assess the safety of increasing doses of IPN01194 in participants with specific types of advanced solid tumours. The aim of this "dose escalation" phase is to find the dose range showing activity on the tumor that can be tolerated by the participants, and to determine the two doses for further testing in Phase IIa. Phase I will assess how the body processes and responds to the study drug when administered with and without food. In Phase IIa, participants with selected single tumour type will be invited to take part. During this phase, the two dose levels of the study drug identified from Phase I will be tested. Participants will take the study drug one of the two dose levels. Each participant will be assigned to a dose level at random (by chance). Each phase will consist of three periods: 1. A period to assess eligibility (screening period) that will take up to 28 days. 2. A treatment period of at least 28 days that will require at least two visits for the first month followed by one visit every month. There will be also one visit, at the end of treatment, at least 30 days after the last administration of study drug. 3. A follow-up period (Phase IIa participants only), where every 3 months, participants will be contacted by phone, until death or the study cut-off date, whichever comes first. Participants will undergo blood samplings, urine collections, physical examinations, and clinical evaluations. They may continue some other medications, but the details need to be recorded. If in the opinion of the investigator a participant is continuing to experience clinical benefit after the cut-off date, the participant may remain in the study and continue to receive the study drug until either disease progression, unacceptable toxicity or other withdrawal criteria are met.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
220
IPN01194 will be taken orally over a period of 28 days (a "Cycle") at the assigned dose level. The dose limiting toxicity (DLT) observation period consists of the first 28 days of treatment with IPN01194 (Cycle 1). Participants will receive IPN01194 treatment beyond Cycle 1 until treatment is precluded by toxicity, disease progression, or upon participant's request or investigator decision.
All participants will receive IPN01194 orally for 28-day cycles at one of the two dose levels determined at the end of Phase I. Participants will receive IPN01194 treatment until treatment is precluded by toxicity, disease progression, or upon participant's request or investigator decision
The Angeles Clinic and Research Institute - California
Los Angeles, California, United States
RECRUITINGUC San Diego Health System - La Jolla
San Diego, California, United States
WITHDRAWNYale Cancer Center - New Heaven
New Haven, Connecticut, United States
RECRUITINGSarah Cannon Research Institute (SCRI) - Nashville
Nashville, Tennessee, United States
RECRUITINGVirginia Cancer Specialist
Fairfax, Virginia, United States
RECRUITINGCentre Léon Bérard - Lyon
Lyon, France
RECRUITINGParis Saint-Louis
Paris, France
RECRUITINGInstitut de Cancerologie de l'Ouest (St-Herblain)
Saint-Herblain, France
RECRUITINGIGR-Villejuif
Villejuif, France
RECRUITINGBarcelona - Val D'Hebron
Barcelona, Spain
RECRUITING...and 2 more locations
Phase 1: Percentage of participants with dose limiting toxicity (DLT)
Time frame: Within 28 days of first dose
Phase 1: Percentage of participants experiencing Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TE SAEs)
An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Time frame: At 30 days following the last administration of study intervention
Phase 1: Percentage of participants with dose interruptions and permanent treatment discontinuations
Time frame: At 30 days following the last administration of study intervention
Phase 2a: Objective response rate (ORR)
Defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) as determined by investigator.
Time frame: At end of treatment (up to approximately 32 months)
Phase 1: Time to maximum observed drug concentration (Tmax) after single and multiple doses of IPN01194
Time frame: At Day 1 and Day 15.
Phase 1: Maximum observed drug concentration (Cmax) after single and multiple doses of IPN01194
Time frame: At Day 1 and Day 15.
Phase 1: Area under the plasma concentration time curve (AUCtau) after single and multiple doses of IPN01194
AUCtau is defined as the concentration of drug over one dosing interval.
Time frame: At Day 1 and Day 15.
Phase 1: Geometric mean ratio of Cmax of IPN01194 administered in fed state relative to fasted state
Time frame: Between Day -8 and Day -3 (fasted period) and between Day -10 and Day -7 (fed state period)
Phase 1: Geometric mean ratio of AUClast of IPN01194 administered in fed state relative to fasted state
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Time frame: Between Day -8 and Day -3 (fasted period) and between Day -10 and Day -7 (fed state period)
Phase 1: Geometric mean ratio of AUCinf administered in fed state relative to fasted state
AUCinf is defined as the concentration of drug extrapolated to infinite time.
Time frame: Between Day -8 and Day -3 (fasted period) and between Day -10 and Day -7 (fed state period)
Phase 1: Prolongation of corrected QT interval (QTc)
Prolongation of QTc defined as the upper limit of 90% confidence interval for change from baseline QTc evaluated over Cycle 1 at the highest clinically relevant exposure.
Time frame: Within 28 days of first dose
Phase 1: Objective response rate (ORR)
The ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR).
Time frame: At end of treatment (up to approximately 32 months)
Phase 2a: Duration of response (DoR)
Defined as the percentage of participants with BOR of CR or PR, as determined by investigator per RECIST version 1.1
Time frame: From randomisation to end of treatment (up to approximately 32 months)
Phase 2a: Progression-free survival (PFS)
PFS is defined as the time from the date of randomisation to the date of the first documented disease progression, as determined by investigator per RECIST version 1.1.
Time frame: From randomisation to end of treatment (up to approximately 32 months)
Phase 2a: PFS rate at 4 months
Time frame: From randomisation to 4 months
Phase 2a: Disease control rate (DCR)
DCR is defined as the percentage of participants with BOR of CR, PR or stable disease (SD), as determined by investigator per RECIST version 1.1.
Time frame: At end of treatment (up to approximately 32 months)
Phase 2a: Percentage of participants with TEAEs and TE SAEs
Time frame: At end of treatment (up to approximately 32 months)
Phase 2a: Percentage of participants with dose interruptions and permanent treatment discontinuations
Time frame: At end of treatment (up to approximately 32 months)
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