A Phase I, Open-Label, Multiple Ascending Dose Study of RRx-001 and Nivolumab

NCT02518958 | Completed Phase 1

• 1 other identifier: RRx001-14-02
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a dose escalation protocol to determine the feasibility of co-administration of RRx-001 and nivolumab. Immune surveillance is an endogenous mechanism to cause remission of neoplastic growth. Epigenetic agents like RRx-001 are associated not only with enhanced gene transcription and restored expression of silenced genes but also with increased expression of pro-inflammatory mediators, upregulation of PD-L1 on tumor cells and de-repression of antigens that promote immune recognition of tumors. It is hypothesized that RRx-001, will prime or sensitize to immune checkpoint therapy targeting PD-1 interaction with nivolumab.

Conditions

Malignant Solid Tumor; Lymphoma

Outcome Measures

Primary Outcomes (1)

• Number, frequency and type of adverse events

  23 weeks

Secondary Outcomes (4)

• Time to Tumor Progression (TTP)

  23 weeks

• Overall Survival

  2 years

• Clinical benefit Rate

  23 weeks

• Progression-Free Survival (PFS)

  23 weeks

Study Arms (1)

RRx-001 + Nivolumab

EXPERIMENTAL

Patients enrolled in this trial will receive study drug (RRx-001) on Day 1 as a single agent. Nivolumab (3 mg/kg) will be administered on Day 2 or Day 3 as a single agent.

Drug: RRx-001; Drug: Nivolumab

Interventions

RRx-001 DRUG

RRx-001 + Nivolumab

Nivolumab DRUG

RRx-001 + Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of an advanced, malignant, solid tumor(s) or lymphoma that are either refractory or is intolerant to, or has refused all standard available life-prolonging therapies.
• Measurable or evaluable disease based on RECIST criteria version. 1.1.
• ECOG performance status is 0-2 at Screening.
• Acceptable liver function at Screening,
• Serum creatinine \< 2x institution upper limit of normal
• Acceptable hematologic status at Screening
• 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.

You may not qualify if:

• Serious co-morbid medical condition, or a clinically significant laboratory finding(s) that, in the opinion of the Investigator, suggests the presence of an infectious, endocrine, and/or other inadequately treated systemic disorder.
• If female, subject is pregnant and/or breastfeeding.
• Subjects with active autoimmune disease or history of autoimmune disease that might recur and may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded.
• Subjects having a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration.
• Prior therapy with any antibody/drug that targets the T cell coregulatory proteins, including but not limited to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, and anti-CD40 antibodies. However, prior exposure to RRx-001 is allowed.

Sponsors & Collaborators

• EpicentRx, Inc.: lead

Study Sites (1)

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889, United States

Location

Related Publications (1)

• Reid T, Oronsky B, Caroen S, Quinn M, Williams J, Cabrales P, Abrouk N. Phase 1 pilot study of RRx-001 + nivolumab in patients with advanced metastatic cancer (PRIMETIME). Front Immunol. 2023 Mar 7;14:1104753. doi: 10.3389/fimmu.2023.1104753. eCollection 2023.

  PMID: 36960054 DERIVED

MeSH Terms

Conditions

Lymphoma

Interventions

RRx-001; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Bryan Oronsky, MD

  EpicentRx, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2015
• First Posted: August 10, 2015
• Study Start: July 21, 2015
• Primary Completion: May 17, 2016
• Study Completion: September 12, 2016
• Last Updated: November 18, 2019

Record last verified: 2019-11

Locations

US (1)