A Phase I Safety and Pharmacokinetic Study of Gamitrinib Administered Intravenously to Patients With Advanced Cancer
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorFox Chase Cancer Center
About this trial
This is a first-in-human, phase I, open-label, non-randomized dose-escalation and dose-expansion study with the primary objective to determine the safety profile of small molecule, mitochondrial-targeted Hsp90 inhibitor, gamitrinib, including identification of dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) in patients with advanced cancers. A secondary objective of the study is to determine the recommended dose and regimen(s) for a phase II study. This study is based on preclinical data demonstrating the anticancer activity, unique mechanism of action and preliminary safety of gamitrinib.
In the dose-finding portion of this study, gamitrinib formulated in Lipoid S100®-based formulation will be administered as a 1-hour IV infusion once weekly for four weeks as 28-day treatment cycles. Up to 36 patients will be enrolled in the dose-escalation component of the study based on anticipated cohorts. The starting dose will be 10 mg, corresponding to allometric scaling) from the most sensitive species (rats) in the 29-day GLP toxicology and toxicokinetic studies with 14-day recovery period of gamitrinib. Dose-escalation will follow a 3+3 design. Six patients will be enrolled in the dose-expansion component of the study at MTD for the purpose of exploring pharmacodynamic effects via tumor pre and on-therapy biopsies.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histologically confirmed diagnosis of advanced cancer refractory to standard of care therapy, or for whom no standard of care therapy is available. Any numbers of prior therapies are allowed.
Dose escalation phase: Solid tumors and lymphoma may have measurable or evaluable disease as per Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1) or as per RECIL 2017 criteria
All previous therapies of cancer, including radiotherapy major surgery and investigational therapies must be discontinued for ≥14 days (≥ 28 days for mitomycin C or nitrosoureas) before Cycle 1 Day 1 (C1D1), and all acute effects of any prior therapy must have resolved to baseline severity or Grade ≤ 1 Common Terminology Criteria for Adverse Events (CTCAE v5), except alopecia or parameters defined in this eligibility list.
Age > 18 years.
Disqualifiers
Patients with symptomatic brain metastases are excluded. Patients with asymptomatic and treated CNS metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases > 28 days prior to study entry, including radiotherapy or surgery. Concurrent use of steroids for the treatment of brain metastasis are not permitted.
Current treatment on another (therapeutic) clinical trial
Hypertension not adequately controlled with medications (>150/100 mm Hg despite optimal medical therapy)
Active bacterial fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), requiring treatment with IV antibiotic, IV anti-fungal, or anti-viral (Testing is not required for eligibility).
Trial design
Design model
Sequential
Treatments tested in this trial
Gamitrinib
DrugThis is a first-in-human, phase I, open-label, non-randomized dose-escalation and dose-expansion study with the primary objective to determine the safety profile of small molecule, mitochondrial-targeted Hsp90 inhibitor, gamitrinib, including identification of dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) in patients with advanced cancers. A secondary objective of the study is to determine the recommended dose and regimen(s) for a phase II study. This study is based on preclinical data demonstrating the anticancer activity, unique mechanism of action and preliminary safety of gamitrinib.
Treatment groups
42 Participants
are divided into 7 treatment groups7
Treatment groupsSee each treatment group below.
Group A: Dose -1Experimental treatment 1 intervention
Group B: Dose 1Experimental treatment 1 intervention
Group C: Dose 2Experimental treatment 1 intervention
Group D: Dose 3Experimental treatment 1 intervention
Group E: Dose 4Experimental treatment 1 intervention
Group F: Dose 5Experimental treatment 1 intervention
Group G: Dose 6Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Determine the MTD and/or RP2D of gamitrinib when administered once weekly.
First cycle dose-limiting toxicities. The maximally tolerated dose (MTD) is defined as the dose level below which the absolute observed DLT rate is \> 25%. The MTD is equivalent to the anticipated recommended phase 2 dose (RP2D).
Time frame
7 yearsSecondary outcomes
1
Evaluate the overall safety profile of intravenously administered single-agent gamitrinib
Overall, safety profile of gamitrinib as characterized by type, frequency, severity, timing and relationship to study therapy of adverse events and laboratory abnormalities according to NCI CTCAE v5.0.
Time frame
7 years2
To evaluate the peak concentration (Cmax) of gamitrinib
Blood sample will be collected for determination of gamitrinib plasma concentrations. The PK parameter to be evaluated includes peak concentration (Cmax).
Time frame
7 years3
To evaluate the area under the concentration time curve (AUC0-t) of gamitrinib
Blood sample will be collected for determination of gamitrinib plasma concentrations. PK parameter to be evaluated includes area under the concentration time curve (AUC0-t).
Time frame
7 years4
To evaluate the clearance (CL) of gamitrinib
Blood sample will be collected for determination of gamitrinib plasma concentrations. PK parameter to be evaluated includes clearance (CL).
Time frame
7 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Fox Chase Cancer Center
Lead sponsor
National Institutes of Health (NIH)
Collaborator
National Cancer Institute (NCI)
Collaborator
Source ClinicalTrials.gov