The primary objective of the phase 1 trial is to identify a dose of topotecan that will be safe to take forward into a Phase 2 trial, with no unexpected toxicities or drug-drug interactions with standard therapy for COVID-19. The investigators hypothesise that a single dose of low-dose Topotecan will blunt the expression of inflammatory genes in patients with moderate COVID-19, without cytotoxic side effects.
4 fixed dosing levels (0.25 -0.5mg) of Topotecan will be evaluated in this trial, using sub-cytotoxic doses of Topotecan which are well below typical chemotherapy levels and shown not to cause myelosuppression in previously tested populations. The dose escalation will be in a standard 3+3 dose escalation design with 0.25 mg increments of Topotecan. The study aims to establish the recommended phase 2 dose (RP2D) of Topotecan in hypoxic patients with moderate to severe COVID-19.The RP2D is defined as the maximum safe dose at which 3 or more patients are found to have clinically relevant concentrations of Topotecan in the blood stream, without reaching anti-cancer concentrations in plasma (defined as Area under the curve (AUC)\>150000) and without causing Grade 2/3/4 neutropenia (CTCAE5).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Topotecan hydrochloride is a semi-synthetic derivative of camptothecin and is an anti-tumor drug with topoisomerase I-inhibitor activity. It is a well-established chemotherapeutic agent used for cancer treatment.
Christian Medical College
Vellore, Tamil Nadu, India
RECRUITINGMaximal tolerable dose of Topotecan
To determine a maximal dose of Topotecan, at which less than 1 out of 3 patients exhibit anti-cancer concentrations in plasma, or have G2/3/4 neutropenia
Time frame: 24 hours and 14 days from the time of Topotecan administration
Rate of reduction in the duration of supplemental oxygen requirement in participants
Determine effect of Topotecan on duration of additional oxygen requirements
Time frame: 1 week from administration of Topotecan
Rate of treatment related CTCAE grade 3/4 haematological toxicity
Dose limiting toxicities will be graded using CTCAE version 5.0.
Time frame: Up to Day 10 from Topotecan administration
Number of participant with Serious Adverse Events
Serious Adverse Events experience by subject after Topotecan administration (related and unrelated).
Time frame: Within 14 days from Topotecan administration
Proportion of patients requiring ICU care
Number of patients requiring intubation/inotropic/vasopressor support
Time frame: 28 days from Topotecan administration
Proportion of patients requiring mechanical ventilation
Number of patients requiring mechanical ventilation
Time frame: 28 days from Topotecan administration
Time to discharge
Time to hospital discharge in days
Time frame: 28 days from Topotecan administration
Anand JEYASEKHARAN
CONTACT
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Proportion of patients with secondary infections
Number of patients with secondary infections
Time frame: 28 days from Topotecan administration
Proportion of patients who died after enrolment into trial
Death from related and unrelated causes
Time frame: 28 days from Topotecan administration