RRx-001 in Combination With Irinotecan in Metastatic or Advanced Cancer (PAYLOAD)

Study Overview
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Brief Summary
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This is a phase 1 open-label trial to evaluate the safety, pharmacodynamics and clinical activity of RRx-001 administered in combination with irinotecan. RRx-001 is associated with resensitization to irinotecan in tumors that are previously refractory. This effect has been attributed to the ability of RRx-001 to restore the expression of aberrantly silenced genes, thus re-establishing pathway functions. However, resensitization may have more than one mechanism, among them Pgp pump inhibition and vascular modulation, leading to improved penetration of standard chemotherapy.

Detailed Description
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This dose escalation study consists of 5 sequential dose cohorts each administered RRx-001 with irinotecan. After the first 3 subjects of each cohort complete Cycle 1, the safety will be assessed before moving to the next dose level. Subjects in the current cohort will continue treatment immediately following the completion of Cycle 1, for as long as therapy is tolerated and the RECIST v.1.1 definition of progression is not met.

Official Title
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A Phase I, Open-Label, Multiple Ascending Dose Study to Assess the Safety and Tolerability of RRx-001 in Combination With Irinotecan in Metastatic or Advanced Cancer Patients Without Life-Prolonging Therapies of Demonstrated Clinical Benefit (PAYLOAD)

Conditions
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Malignant Solid Tumor, Metastatic Cancer, Advanced Cancer

Intervention / Treatment
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* Drug: RRx-001
* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of an advanced, malignant, solid tumor(s) with all standard treatment options having been exhausted or declined. Eastern Cooperative Group (ECOG) performance status is 0-2 at Screening. Measurable disease per RECIST v1.1 by radiographic techniques Acceptable liver function, serum creatinine and hematological status Female subjects of childbearing potential, and male subjects with partners of childbearing potential, must agree to use medically acceptable methods of contraception beginning on Study Day 1 and continuing until at least four weeks after administration of the subject's final dose of RRx-001. Subjects with brain metastases are eligible Exclusion Criteria: Concurrent anticancer therapy; however, radiotherapy is allowed Any history of hypersensitivity to irinotecan Cholangitis that required treatment or intervention within 4 weeks of study enrollment Bilirubin > 2.0 mg/dL Serious medical or psychiatric illness likely to interfere with participation in this clinical study If female, subject is pregnant and/or breastfeeding. UGT1A1*28 homozygote or heterozygote BMI >35

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RRx-001 + Irinotecan<br>Cohorts of participants with an advanced, malignant, solid tumor(s) will receive weekly doses of RRx-001 for 3 weeks, switching at week 4 to every-other-week treatments of RRx-001 with irinotecan. | Drug: RRx-001<br> <br> Drug: Irinotecan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number, frequency and type of adverse events |  | 14 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of clinical benefit rate | Duration of clinical benefit (Stable disease or better) using Response Evaluation Criteria in Solid Tumors [RECIST v1.1] criteria | 1 year | 
| Progression-Free Survival | Progression-Free Survival (PFS) using Response Evaluation Criteria in Solid Tumors | 1 year | 
| Overall Response rate | Proportion of patients with reduction in tumor burden using Response Evaluation Criteria in Solid Tumors | 1 year | 
| Overall Survival |  | 2 years |