Phase I Study of RiMO-301 With Radiation in Advanced Tumors

Study Overview
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Brief Summary
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This is a prospective, open-label, single arm, non-randomized study of RiMO-301 with radiation in patients with advanced tumors. A single escalation dose of RiMO-301 is intratumorally injected in a 3 + 3 study design to identify the recommended dose and dosing volumes. Condition or Disease: Patient with advanced tumor which is clinically accessible for intratumoral injection Intervention/Treatment: Drug - RiMO-301 Radiation - Radiotherapy Phase: Phase 1

Detailed Description
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Primary Objectives: • The primary objective is to determine the maximum tolerated dose (MTD) of RiMO-301 as determined by toxicity observed in patients treated with palliative radiation doses Secondary Objectives: To determine clinical response after RiMO-301 and radiotherapy as assessed by clinical response rate using clinical evaluation, imaging and/or symptom relief To characterize adverse events of RiMO-301 in patients with advanced cancers To evaluate the pharmacokinetics (PK) of RiMO-301 with radiation The target population is patients with clinically accessible lesions for intratumoral injection. Up to 3 dose levels (5%, 10%, and 15% of the total baseline tumor volume, respectively) will be tested in a 3 + 3 dose escalation study design. MTD will be defined as the dose associated with a dose limiting toxicity (DLT) in less than or equal to 33% of patients at the dose level tested. Dose limiting toxicity (DLT) is defined as one of the following events occurring from the intratumor injection of RiMO-301 to 30 days after the completion of radiation treatment: Grade 4 or greater treatment related hematologic or dermatologic toxicity Any Grade 3 or greater treatment related non-hematologic, non-dermatologic toxicity (excluding nausea, vomiting or diarrhea without maximal medical intervention)

Official Title
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Phase I Dose-Escalating Study of RiMO-301 With Radiation in Advanced Tumors

Conditions
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Advanced Tumors

Intervention / Treatment
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* Drug: RiMO-301


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of advanced or metastatic cancer not amenable to curative therapy Lesion that is amenable to palliative radiotherapy Lesion that is technically feasible to irradiation and accessible for direct intratumoral injection Target tumor in region not in previously irradiated field Patient must have recovered from acute toxic effects (≤ grade 1) of previous cancer treatments prior to enrollment Age >18 years Has measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion Females with child bearing age should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to the start of dosing Patients must sign a study-specific informed consent form prior to study entry Exclusion Criteria: Patients with a histological diagnosis of lymphomas and/or leukemias Patients may not have received chemotherapy, targeted therapies, biologic response modifiers and/or hormonal therapy within the last 14 days Ongoing clinically significant infection at or near the incident lesion Major surgery over the target area (excluding placement of vascular access) <21 days from beginning of the study drug or minor surgical procedures <7 days Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that would make the patient inappropriate for enrollment in this study Has any mental or medical condition that prevents the patient from giving informed consent or participating in the trial Pregnant and nursing women Patients with a target lesion located in a previously irradiated field

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
Intervention Model: Single Group Assignment
Interventional Model Description: 3 + 3 dose escalation study design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RiMO-301+Radiotherapy<br>3 dose levels (5%, 10%, and 15% of the total baseline tumor volume, respectively) will be tested in a 3 + 3 dose escalation study | Drug: RiMO-301<br>* Drug: RiMO-301 RiMO-301 will be administered by intratumoral route as slow injection Radiotherapy Patients will receive 10 fractions of 3 Gy each over 2 weeks<br>* Other names: Radiotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) | • To determine the maximum tolerated dose (MTD), which is defined as the dose level at which fewer than 33% of patients experience a dose limiting toxicity (DLT) using a 3+3 strategy | 45 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical benefit | • To assess clinical benefit by change in tumor size and resolution of symptoms, which will be reported as response rate (%) | 45 days | 
| adverse effect | • To assess adverse effect as either treatment-related or non-treatment-related as defined by CTCAE | 45 days | 
| Maximum Plasma Concentration [Cmax] | • To evaluate Maximum Plasma Concentration [Cmax] of RiMO-301 in patients tested | 45 days | 
| Area Under the Curve [AUC] | To evaluate Area Under the Curve [AUC] of RiMO-301 in patients tested | 45 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intratumoral