Malignant Solid TumorPhase 1PRIMETIMENCT02518958
A Phase I, Open-Label, Multiple Ascending Dose Study of RRx-001 and Nivolumab
A Phase 1 study testing RRx-001 and Nivolumab in people with Malignant Solid Tumor and Lymphoma, run by EpicentRx, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Solid Tumor, Lymphoma
- What is being tested?
- RRx-001 and Nivolumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jul 2015to 12 Sep 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Malignant Solid Tumor, Lymphoma
- Being tested
- RRx-001, Nivolumab
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RRx-001Drug
NivolumabDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: RRx-001; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number, frequency and type of adverse events
Measured: 23 weeks
Secondary outcomes (4)
Time to Tumor Progression (TTP)
Time to Tumor Progression (TTP) using Response Evaluation Criteria in Solid Tumors [RECIST v1.1] criteria
Measured: 23 weeks
Overall Survival
Measured: 2 years
Clinical benefit Rate
Duration of clinical benefit (Stable disease or better) using Response Evaluation Criteria in Solid Tumors [RECIST v1.1] criteria
Measured: 23 weeks
Progression-Free Survival (PFS)
Progression-Free Survival (PFS) using Response Evaluation Criteria in Solid Tumors [RECIST v1.1] criteria
Measured: 23 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2015 (estimated)
- Study start21 Jul 2015
- Primary completion17 May 2016
- Study completion12 Sep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malignant Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- EpicentRx, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bryan Oronsky, MD, Study director, EpicentRx, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02518958
- Sponsor's protocol ID
- RRx001-14-02
- Acronym
- PRIMETIME
- Status last verified
- Nov 2019
- First submitted
- 4 Aug 2015
- Last updated
- 18 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 36960054
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT02518958
- Acronym / sponsor ID
- PRIMETIME / RRx001-14-02
- Conditions
- Malignant Solid Tumor, Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- EpicentRx, Inc.Industry (pharma, biotech, devices)
- Study start
- 21 Jul 2015 (actual)
- Primary completion
- 17 May 2016 (actual)
- Study completion
- 12 Sep 2016 (actual)
- First posted
- 10 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RRx-001 + Nivolumab | Experimental | Drug: RRx-001, Drug: NivolumabPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RRx-001 | Drug | RRx-001 + Nivolumab |
| Nivolumab | Drug | RRx-001 + Nivolumab |
Primary outcome
Number, frequency and type of adverse events
Time frame: 23 weeks
4 secondary outcomes
Time to Tumor Progression (TTP)
Time frame: 23 weeks
Overall Survival
Time frame: 2 years
Clinical benefit Rate
Time frame: 23 weeks
Progression-Free Survival (PFS)
Time frame: 23 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2019.
- Derived from this study: PubMed 36960054Reid 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bryan Oronsky, MD study director
EpicentRx, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RRx-001 and Nivolumab in people with Malignant Solid Tumor and Lymphoma, run by EpicentRx, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number, frequency and type of adverse events (time frame: 23 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02518958, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2019.