A Phase I, Open-Label, Multiple Ascending Dose Study of RRx-001 and Nivolumab
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Lymphoma |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 5/24/2018 |
| Start Date: | July 21, 2015 |
| End Date: | December 2018 |
A Phase I, Open-Label, Multiple Ascending Dose Study to Assess the Safety and Tolerability of RRx-001 and Nivolumab in Subjects With Advanced Solid Tumors or Lymphomas For Which There Are No Currently Accepted Life-Prolonging Therapies (PRIMETIME)
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.
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.
This is an open-label dose escalation study, consisting of the following periods:
- 1) Screening Period (Up to 16 days): Eligibility for the study will be determined by
Screening tests, physical examination/medical history, and fulfillment of eligibility
criteria. Potential participants are required to provide written informed consent prior
to the performance of any study specific Screening procedures.
- 2) Treatment Period (Day 1 to 57): Between 15 and 45 eligible male and female adult
subjects will receive weekly RRx-001 for a total of nine doses and every other week
nivolumab for a total of 5 doses (odd cycles) or 4 doses (even cycles). Study medication
(RRx-001 and nivolumab) will be administered intravenously at the study center. The
Treatment Period will end following the last dose of nivolumab. Subjects will attend the
study center weekly for on-study assessments.
- 3) Follow-up Period: Subjects that have completed nivolumab dosing will undergo a
follow-up assessment monthly, up to 100 days, for the emergence of delayed toxicity with
particular attention to delayed immune related toxicities.
- 1) Screening Period (Up to 16 days): Eligibility for the study will be determined by
Screening tests, physical examination/medical history, and fulfillment of eligibility
criteria. Potential participants are required to provide written informed consent prior
to the performance of any study specific Screening procedures.
- 2) Treatment Period (Day 1 to 57): Between 15 and 45 eligible male and female adult
subjects will receive weekly RRx-001 for a total of nine doses and every other week
nivolumab for a total of 5 doses (odd cycles) or 4 doses (even cycles). Study medication
(RRx-001 and nivolumab) will be administered intravenously at the study center. The
Treatment Period will end following the last dose of nivolumab. Subjects will attend the
study center weekly for on-study assessments.
- 3) Follow-up Period: Subjects that have completed nivolumab dosing will undergo a
follow-up assessment monthly, up to 100 days, for the emergence of delayed toxicity with
particular attention to delayed immune related toxicities.
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
We found this trial at
1
site
8901 Rockville Pike
Bethesda, Maryland 20889
Bethesda, Maryland 20889
(301) 295-4000
Principal Investigator: Corey Carter, MD
Phone: 301-295-8505
Walter Reed National Military Medical Center The Walter Reed National Military Medical Center is one...
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