A Study to Assess the Safety and Efficacy of Nitric Oxide Injection Into Unresectable Solid Primary or Metastatic Tumors

Study Overview
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Brief Summary
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This is a Phase 1, open-label, dose-escalation and dose-expansion study comprised of a screening period, a single treatment session, and follow-up period of up to Day 60±5 days post-treatment.

Detailed Description
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The purpose of this Phase 1 study is to initiate clinical development of gNO in patients with unresectable cutaneous or subcutaneous primary or metastatic solid tumors that are not amenable or have failed standard treatment, for which no therapy of proven efficacy exists, or which has progressed despite standard therapy. This study of gNO treatment will consist of 2 parts: a dose-escalation part to establish a safe and tolerable dose of gNO in patients with primary or metastatic unresectable cutaneous or subcutaneous solid tumors (Part A), and a dose expansion phase (Part B) which may be initiated at the Sponsor's discretion after the maximum tolerated dose (MTD) (or recommended Phase 2 dose [RP2D]) has been determined in the dose-escalation phase (Part A). This study will be the basis for future studies.

Official Title
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A Phase 1, Open-Label, Dose Escalation and Dose Expansion Study to Assess the Safety and Efficacy of Nitric Oxide Injection Into Unresectable Solid Cutaneous/Subcutaneous Primary or Metastatic Tumors

Conditions
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Cancer

Intervention / Treatment
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* Drug: Nitric Oxide 25,000 ppm
* Drug: Nitric Oxide 50,000 ppm
* Drug: Nitric Oxide 100,000 ppm
* Drug: Nitric Oxide selected dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient (male or female) is at least 18 years of age at the time of signature of the informed consent form. Patient has an ECOG Performance Status score of 0-3 and with a life expectancy of ≥3 months. Patient must have a confirmed diagnosis of at least one unresectable cutaneous or subcutaneous histologically confirmed primary or metastatic solid tumor. No therapy of proven efficacy exists for the tumor, the tumor is not amenable to standard therapies, the tumor has failed to respond to standard therapy or has progressed despite standard therapy. Patient has measurable disease on imaging based on RECIST Version 1.1 or non-measurable disease. Patient have adequate hematologic and organ function. Exclusion Criteria: The tumor is situated in the lymph node, in thyroid, close to trachea or in facial area or other region which, in the Investigator's opinion, can pose extra risk to the patient. Has received prior systemic anti-cancer therapy including investigational agents within 14 days of the start of study treatment. Active central nervous system tumors or metastases.. Received systemic corticosteroid therapy ≤1 week prior to study treatment or any other form of systemic immunosuppressive medication for medically significant acute or chronic conditions. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, neuropathy and protocol-defined laboratory values. Active or prior documented autoimmune or inflammatory disorders. History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of enrolment. Known active infection and uncontrolled intercurrent illness. Receiving drugs that have contraindication with NO.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: In Part A, the following gNO doses will be studied to determine MTD: 25,000 ppm, 50,000 ppm and 100,000 ppm. Once the MTD is determined, additional patients will be treated in Part B Dose Expansion to further characterize the safety and biomarkers of gNO and determine RP2D.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Subjects will receive 25,000 ppm NO | Drug: Nitric Oxide 25,000 ppm<br>* Intratumoral injection of 25,000 gNO<br>* Other names: gNO injection;|
| Experimental: Cohort 2<br>Subjects will receive 50,000 ppm NO | Drug: Nitric Oxide 50,000 ppm<br>* Intratumoral injection of 50000 gNO<br>|
| Experimental: Cohort 3<br>Subjects will receive 100,000 ppm NO | Drug: Nitric Oxide 100,000 ppm<br>* Intratumoral injection of 100,000 gNO<br>|
| Experimental: RP2D Expansion<br>Subjects will receive the RP2D dose of NO | Drug: Nitric Oxide selected dose<br>* Intratumoral injection of selected does on gNO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of AEs, SAEs and DLTs (safety) parameters. | The incidence and characteristics of adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs) and changes in assessed safety parameters. Toxicity will be graded according to NCI CTCAE version 5.0 | up to 60 days from injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intratumoral Injection, Nitric Oxide, single gNO injection