Clinical trial NCT05329103: A Study to Evaluate PEEL-224 in Patients With Advanced Solid Tumors
Official title: An Early Phase Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of PEEL-224 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: Peel Therapeutics Inc
Sponsor class: INDUSTRY
First posted: 2022-04-14
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a first-in-human, dose escalation, repeat-dose, multi-center, open-label study evaluating safety, tolerability, PK, and preliminary antitumor activity of PEEL-224 in patients with advanced solid tumors.

Detailed description: This is a first-in-human, dose escalation, repeat-dose, multi-center, open-label study evaluating safety, tolerability, PK, and preliminary antitumor activity of a novel topoisomerase I inhibitor (PEEL-224) in patients with advanced solid tumors. Dose escalation will be guided by the modified toxicity probability interval-2 (mTPI-2) design with a target toxicity rate of 25% and an acceptable DLT interval of 20% to 30%. Cohorts of 2 or more patients will be sequentially enrolled at progressively higher dose levels of PEEL-224. For each dose level, all patients must complete Cycle 1 before the decision to dose escalate the next cohort of patients is made.

Eligibility criteria: Inclusion criteria:

* Have a diagnosis of colorectal cancer confirmed by local pathology review (histology or cytology) - Part 2 only
* ECOG of 0 or 1
* Have a diagnosis of advanced or metastatic solid tumor that has progressed after prior standard therapy, have been intolerant or ineligible for standard therapy, or have a malignancy for which there is no approved therapy considered standard of care
* Have at least 1 documented measurable lesion as detected by radiological methods at study entry as per Response Evaluation Criteria in Solid Tumors v1.1
* Have adequate bone marrow reserve
* Have adequate liver function
* Have adequate renal function
* Have completed prior anticancer therapy, including investigational agents, ≥28 days or 5 half lives, whichever is shorter, prior to study treatment
* Have resolution of any clinically significant toxic effects of prior therapy

Exclusion criteria:

* Have primary central nervous system tumors
* Have brain or spinal metastases, except if treated by surgery, surgery plus focal radiotherapy, or radiotherapy alone, with no evidence of progression or hemorrhage ≤14 days prior to the first dose of PEEL-224. Have craniospinal radiotherapy ≤12 weeks prior to the first dose of PEEL-224
* Have significant abnormalities in the level of serum electrolytes
* Have received neutrophil growth factor support ≤14 days prior to the first dose of PEEL 224
* Have an active infection ≤14 days prior to the first dose of PEEL-224
* Use of strong cytochrome P450 (CYP)1A2 and CYP3A4 inhibitors and/or inducers ≤14 days prior to the first dose of PEEL-224 or during the study
* Use of systemic corticosteroids ≤14 days prior to the first dose of PEEL-224
* Are known to be HIV-positive, unless CD4 + lymphocyte count ≥ 300/μL, undetectable viral load; AND Receiving anti-retroviral therapy.
* Have uncontrolled hepatitis B infection or hepatitis C infection;
* Are pregnant or lactating, plan to become pregnant, or plan to donate gametes (ova or sperm) for in vitro fertilization during the study period or for 90 days after the patient's last study-related visit (for eligible patients only, if applicable). Eligible female patients unwilling to employ appropriate contraceptive measures to ensure that pregnancy does not occur during the study will be excluded;
* Have evidence of another malignancy ≤2 years prior to screening (except in situ non melanoma skin cell cancers and in situ cervical carcinoma);
* Are currently enrolled in another therapeutic clinical study or a non-therapeutic clinical study that will conflict with scheduled visits required by this study;
* Have clinically significant, uncontrolled cardiovascular disease
* Have history of cerebrovascular accident, transient ischemic attack, or thrombosis requiring treatment ≤3 months prior to the first dose of PEEL-224
* Have received or will receive a live vaccine ≤14 days prior to the first dose of PEEL 224.
* Have tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection ≤14 days of the Screening Visit.

Primary outcomes:
measure: Determine maximum tolerated dose
timeFrame: 28 days
Secondary outcomes:
measure: Overall safety and tolerability of PEEL-224
timeFrame: through study completion, expected average of 6 months
measure: Antitumor activity assessment
timeFrame: every 8 weeks through study completion, expected average of 6 months
measure: Cmax of PEEL-224 and its metabolite
timeFrame: Through 96 hours after dosing on Cycle 1 Day 1 and through 168 hours hours of dosing on Cycle 1 Day 15
measure: Tmax of PEEL-224 and its metabolite
timeFrame: Through 96 hours after dosing on Cycle 1 Day 1 and through 168 hours hours of dosing on Cycle 1 Day 15
measure: changes in QTcF/QTcBBB
timeFrame: Through Cycle 1 (28 days)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institiute
state: Arizona
city: Palo Alto
country: United States
facility: Stanford Cancer Center
state: California
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Philadelphia
country: United States
facility: Abramson Cancer Center at Pennsylvania Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute, University of Utah
state: Utah
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
Study officials:
References: