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

Phase 1
Terminated
Conditions
Metastatic Cancer
Malignant Solid Tumor
Advanced Cancer
Interventions
Registration Number
NCT02801097
Lead Sponsor
EpicentRx, Inc.
Brief Summary

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

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
28
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
RRx-001 + IrinotecanRRx-001Cohorts 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.
RRx-001 + IrinotecanIrinotecanCohorts 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.
Primary Outcome Measures
NameTimeMethod
Number, frequency and type of adverse events14 Weeks
Secondary Outcome Measures
NameTimeMethod
Overall Response rate1 year

Proportion of patients with reduction in tumor burden using Response Evaluation Criteria in Solid Tumors

Overall Survival2 years
Duration of clinical benefit rate1 year

Duration of clinical benefit (Stable disease or better) using Response Evaluation Criteria in Solid Tumors \[RECIST v1.1\] criteria

Progression-Free Survival1 year

Progression-Free Survival (PFS) using Response Evaluation Criteria in Solid Tumors

Trial Locations

Locations (2)

Rutgers Cancer Institute of New Jersey

🇺🇸

New Brunswick, New Jersey, United States

University of California, Davis

🇺🇸

Sacramento, California, United States

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