Carcinoma, Small Cell LungPhase 3REPLATINUMNCT05566041
A Phase 3, Controlled, Open-label, Global Randomized Study of RRx-001 With a Platinum Doublet or a Platinum Doublet in Small Cell Lung Cancer
A Phase 3 study testing RRx-001 + eLOOP Device and Cisplatin/carboplatin plus etoposide in people with Carcinoma, Small Cell Lung, run by EpicentRx, Inc. at 2 sites in United States.
Trial summary
This Global Phase 3 study aims to find out whether RRx-001 + platinum chemotherapy is more effective than platinum chemotherapy alone in 3rd line or beyond small cell cancer. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Carcinoma, Small Cell Lung
- What is being tested?
- RRx-001 + eLOOP Device and Cisplatin/carboplatin plus etoposide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 292 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Aug 2022to 31 Dec 2025
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 and ≤ 80 years
- Prior platinum treatment is required
- Prior treatment with a checkpoint inhibitor is required unless contraindicated.
- Patient must have received at least 2 prior lines of therapy
- Biopsy confirmation of small cell lung cancer
- Capable of providing informed consent and complying with trial procedures
- Measurable disease by RECIST 1.1. Measurable lesions will be confirmed by imaging (CT scan)
- Performance Status (ECOG) 0-2
Who cannot join
- Symptomatic central nervous system metastases or neurologically unstable patients that are on increasing steroid dose.
- The presence of another primary malignancy (excluding in situ of the cervix or basal carcinoma of the skin)
- Treatment of SCLC with any antineoplastic agent with the exception of steroids.
- Patients with clinically significant illnesses which would compromise participation in the study, including, but not limited to active or uncontrolled infection, immune deficiencies, Hepatitis B, Hepatitis C, uncontrolled diabetes, uncontrolled hypertension, certain heart conditions, or mental illness/social situations that would limit compliance with study requirements.
- History of an allergic reaction to previously received platinum-based regimen, or history of having to discontinue previously received platinum-based regimen secondary to toxicity (excluding hematologic toxicity)
- Any clinical laboratory findings, which give reasonable suspicion of a disease or condition that contraindicates the use of any study medication or renders the patient at high risk from treatment
Show all 9Show fewer
- Uncontrolled or symptomatic pleural or pericardial effusion
- Pregnant or nursing. There is a potential for congenital abnormalities and for this regimen to harm nursing infants
- Virologic, serologic, or clinical evidence of active SARS-CoV-2 infection
Trial locations and contacts
2 sites in 1 country.
United States2 sites
H. Lee Moffitt Cancer Center & Research Institute, Inc.
Tampa, Florida, 33612
The University of Kansas Cancer Center
Westwood, Kansas, 66205
About this study
Official title: REPLATINUM: A Phase 3, Controlled, Open-label, Global Randomized Study of RRx-001 Administered Sequentially With a Platinum Doublet or a Platinum Doublet in Third-Line or Beyond Small Cell Lung Cancer
This Global Phase 3 study aims to find out whether RRx-001 + platinum chemotherapy is more effective than platinum chemotherapy alone in 3rd line or beyond small cell cancer.
Read the detailed description
Small cell cancer (SCC), which mostly arises in the lungs but also in other parts of the body as well such as the prostate and the intestines, is one of the most aggressive forms of cancer; in fact, SCC is so aggressive that in 2012 Congress designated it a recalcitrant or difficult-to-treat cancer, along with pancreatic cancer and glioblastoma or GBM, a primary tumor of the brain, which share the terrible "distinction" of having a 5 year survival rate less than 50%.
One of the main reasons that SCC is so recalcitrant or difficult-to-treat has to do with the development of resistance. Almost all cancers (and SCC is no exception) are treated according to lines of therapy. A line of therapy is a particular course of treatment or treatment regimen. So, in SCC, the first line of treatment is a platinum doublet, with the word doublet meaning two, and consists of the double chemotherapy regimen of cisplatin or carboplatin + etoposide. Most patients initially respond well to the platinum doublet but unavoidably, as a matter of course, resistance to treatment develops and, with that development, a new treatment in second line is started. The same pattern is followed in later lines of therapy: resistance in second line leads to the start of another treatment in 3rd line, and with resistance in 3rd line, which is, unfortunately, just as inevitable, and usually happens even sooner, since the later the line of therapy the more aggressive the tumor, a 4th line treatment is started and so on and so forth until, eventually, no lines of treatment are left. The implicit or unwritten rule in cancer therapy is that once resistance occurs on a particular treatment that same treatment is never reintroduced or restarted.
RRx-001 is a form of immunotherapy that has the potential to overturn this unwritten rule by sensitizing tumors, in other words, by making them more sensitive to the platinum doublet that they received in first line. This is very important because, as previously stated, the platinum doublet is usually the most effective therapy, so it is a benefit to patients if sensitivity to the platinum doublet is restored or increased (even in cases where no response ever occurred) and now they respond as if they were in 1st line rather than in 3rd line or beyond.
In this study, which is called REPLATINUM, because patients will be reintroduced to or restarted on a platinum doublet, there is a 50% chance of receiving either RRx-001 + platinum doublet in Arm 1 or a platinum doublet without RRx-001 in Arm 2. However, patients in arm 2 whose cancer progresses or gets worse (as determined by imaging scans), have the opportunity to "cross-over" to Arm 1 and receive RRx-001 + platinum doublet until such time as their cancer progresses. In this way, all patients, even those on Arm 2, are potentially eligible to be treated with RRx-001.
- Conditions
- Carcinoma, Small Cell Lung
- Being tested
- RRx-001 + eLOOP Device, Cisplatin/carboplatin plus etoposide
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RRx-001 + eLOOP DeviceDrug
RRx-001 is a small molecule anticancer drug which is mixed with patient's own blood using the eLOOP device
Drug: Cisplatin/carboplatin plus etoposide Standard of care platinum doublet chemotherapy
Cisplatin/carboplatin plus etoposideDrug
Standard of care platinum doublet chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | RRx-001 + eLOOP Device 4 mg IV infusion once weekly for 3 weeks
Cisplatin/carboplatin plus etoposide (up to 4 cycles):
Cisplatin or Carboplatin:
Cisplatin initially dosed at 60 mg/m2 on Day 1 every 3 weeks OR Carboplatin initially dosed at an AUC (area under the curve) of 5 on Day 1 every 3 weeks Etoposide to be given per the initial approval by the package insert (USPI FDA) at 100 mg/m2 Days 1-3 every 3 weeks Receives: Drug: RRx-001 + eLOOP Device |
| Arm 2 | Active comparator | Cisplatin/carboplatin plus etoposide (up to 4 cycles):
Cisplatin or Carboplatin:
Cisplatin initially dosed at 60 mg/m2 on Day 1 every 3 weeks OR Carboplatin initially dosed at an AUC of 5 on Day 1 every 3 weeks Etoposide to be given per the initial approval by the package insert (USPI FDA) at 100 mg/m2 Days 1-3 every 3 weeks Receives: Drug: Cisplatin/carboplatin plus etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS) and Overall Survival (OS)
To compare the co-primary efficacy endpoints comprising progression free survival (PFS) and overall survival (OS). PFS is defined as the time from randomization until disease progression or all-cause mortality between the two arms. Disease progression is assessed by the blinded independent central review (BICR) via RECIST 1.1, and is the basis for the principal definition of PFS. OS is defined as the time from randomization to all-cause mortality
Measured: Estimated up to 12 Months
Secondary outcomes (1)
Overall Response Rate (ORR)
To compare overall response rate (ORR, as assessed by the BICR via RECIST 1.1), between the two arms Duration of response will also be characterized and compared between the two arms
Measured: Estimated up to 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2022
- Study start1 Aug 2022
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Small Cell LungStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- In this study, patients will be randomized to 1 of 2 groups or arms. Patients in Arm 1 will receive the study drug, RRx-001, once a week for 3 weeks followed by up to 4 cycles of platinum doublet (platinum plus etoposide) chemotherapy. Patients with stable disease or better will go on to the Platinum Stacking Phase and will receive RRx-001 once a week for 2 weeks followed by 2 cycles of single agent platinum chemotherapy in a repeating pattern until such time as their cancer gets worse.. Patients in Arm 2 will receive the standard of care platinum doublet (platinum plus etoposide) chemotherapy for up to 4 cycles. . Patients in arm 2 whose cancer gets worse (as determined by imaging scans), may "cross-over" to the Platinum Stacking Phase of Arm 1 (see study schema below).
- Masking
- None (open label)
- Enrolment
- 292 participants (estimated)
Sponsor and investigators
- Lead sponsor
- EpicentRx, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Sciclone Pharmaceuticals (China) Co., Ltd.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05566041
- Sponsor's protocol ID
- EpicentRx
- Acronym
- REPLATINUM
- Status last verified
- Oct 2024
- First submitted
- 30 Sep 2022
- Last updated
- 31 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- REPLATINUM: A Phase 3, Controlled, Open-label, Global Randomized Study of RRx-001 Administered Sequentially With a Platinum Doublet or a Platinum Doublet in Third-Line or Beyond Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT05566041
- Acronym / sponsor ID
- REPLATINUM / EpicentRx
- Conditions
- Carcinoma, Small Cell Lung
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 292 participants (estimated)
- Lead sponsor
- EpicentRx, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Sciclone Pharmaceuticals (China) Co., Ltd.
- Study start
- 1 Aug 2022 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 4 Oct 2022 (actual)
- 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 Global Phase 3 study aims to find out whether RRx-001 + platinum chemotherapy is more effective than platinum chemotherapy alone in 3rd line or beyond small cell cancer.
Detailed description
Small cell cancer (SCC), which mostly arises in the lungs but also in other parts of the body as well such as the prostate and the intestines, is one of the most aggressive forms of cancer; in fact, SCC is so aggressive that in 2012 Congress designated it a recalcitrant or difficult-to-treat cancer, along with pancreatic cancer and glioblastoma or GBM, a primary tumor of the brain, which share the terrible "distinction" of having a 5 year survival rate less than 50%.
One of the main reasons that SCC is so recalcitrant or difficult-to-treat has to do with the development of resistance. Almost all cancers (and SCC is no exception) are treated according to lines of therapy. A line of therapy is a particular course of treatment or treatment regimen. So, in SCC, the first line of treatment is a platinum doublet, with the word doublet meaning two, and consists of the double chemotherapy regimen of cisplatin or carboplatin + etoposide. Most patients initially respond well to the platinum doublet but unavoidably, as a matter of course, resistance to treatment develops and, with that development, a new treatment in second line is started. The same pattern is followed in later lines of therapy: resistance in second line leads to the start of another treatment in 3rd line, and with resistance in 3rd line, which is, unfortunately, just as inevitable, and usually happens even sooner, since the later the line of therapy the more aggressive the tumor, a 4th line treatment is started and so on and so forth until, eventually, no lines of treatment are left. The implicit or unwritten rule in cancer therapy is that once resistance occurs on a particular treatment that same treatment is never reintroduced or restarted.
RRx-001 is a form of immunotherapy that has the potential to overturn this unwritten rule by sensitizing tumors, in other words, by making them more sensitive to the platinum doublet that they received in first line. This is very important because, as previously stated, the platinum doublet is usually the most effective therapy, so it is a benefit to patients if sensitivity to the platinum doublet is restored or increased (even in cases where no response ever occurred) and now they respond as if they were in 1st line rather than in 3rd line or beyond.
In this study, which is called REPLATINUM, because patients will be reintroduced to or restarted on a platinum doublet, there is a 50% chance of receiving either RRx-001 + platinum doublet in Arm 1 or a platinum doublet without RRx-001 in Arm 2. However, patients in arm 2 whose cancer progresses or gets worse (as determined by imaging scans), have the opportunity to "cross-over" to Arm 1 and receive RRx-001 + platinum doublet until such time as their cancer progresses. In this way, all patients, even those on Arm 2, are potentially eligible to be treated with RRx-001.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- In this study, patients will be randomized to 1 of 2 groups or arms. Patients in Arm 1 will receive the study drug, RRx-001, once a week for 3 weeks followed by up to 4 cycles of platinum doublet (platinum plus etoposide) chemotherapy. Patients with stable disease or better will go on to the Platinum Stacking Phase and will receive RRx-001 once a week for 2 weeks followed by 2 cycles of single agent platinum chemotherapy in a repeating pattern until such time as their cancer gets worse.. Patients in Arm 2 will receive the standard of care platinum doublet (platinum plus etoposide) chemotherapy for up to 4 cycles. . Patients in arm 2 whose cancer gets worse (as determined by imaging scans), may "cross-over" to the Platinum Stacking Phase of Arm 1 (see study schema below).
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: RRx-001 + eLOOP DeviceRRx-001 + eLOOP Device 4 mg IV infusion once weekly for 3 weeks Cisplatin/carboplatin plus etoposide (up to 4 cycles): Cisplatin or Carboplatin: Cisplatin initially dosed at 60 mg/m2 on Day 1 every 3 weeks OR Carboplatin initially dosed at an AUC (area under the curve) of 5 on Day 1 every 3 weeks Etoposide to be given per the initial approval by the package insert (USPI FDA) at 100 mg/m2 Days 1-3 every 3 weeks |
| Arm 2 | Active comparator | Drug: Cisplatin/carboplatin plus etoposideCisplatin/carboplatin plus etoposide (up to 4 cycles): Cisplatin or Carboplatin: Cisplatin initially dosed at 60 mg/m2 on Day 1 every 3 weeks OR Carboplatin initially dosed at an AUC of 5 on Day 1 every 3 weeks Etoposide to be given per the initial approval by the package insert (USPI FDA) at 100 mg/m2 Days 1-3 every 3 weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 18 and ≤ 80 years
- Prior platinum treatment is required
- Prior treatment with a checkpoint inhibitor is required unless contraindicated.
- Patient must have received at least 2 prior lines of therapy
- Biopsy confirmation of small cell lung cancer
Key exclusion criteria (9 listed)
- Symptomatic central nervous system metastases or neurologically unstable patients that are on increasing steroid dose.
- The presence of another primary malignancy (excluding in situ of the cervix or basal carcinoma of the skin)
- Treatment of SCLC with any antineoplastic agent with the exception of steroids.
- Patients with clinically significant illnesses which would compromise participation in the study, including, but not limited to active or uncontrolled infection, immune deficiencies, Hepatitis B, Hepatitis C, uncontrolled diabetes, uncontrolled hypertension, certain heart conditions, or mental illness/social situations that would limit compliance with study requirements.
- History of an allergic reaction to previously received platinum-based regimen, or history of having to discontinue previously received platinum-based regimen secondary to toxicity (excluding hematologic toxicity)
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 + eLOOP DeviceRRx-001 is a small molecule anticancer drug which is mixed with patient's own blood using the eLOOP device Drug: Cisplatin/carboplatin plus etoposide Standard of care platinum doublet chemotherapy | Drug | Arm 1 |
| Cisplatin/carboplatin plus etoposideStandard of care platinum doublet chemotherapy | Drug | Arm 2 |
Primary outcome
Progression Free Survival (PFS) and Overall Survival (OS)
Time frame: Estimated up to 12 Months
To compare the co-primary efficacy endpoints comprising progression free survival (PFS) and overall survival (OS). PFS is defined as the time from randomization until disease progression or all-cause mortality between the two arms. Disease progression is assessed by the blinded independent central review (BICR) via RECIST 1.1, and is the basis for the principal definition of PFS. OS is defined as the time from randomization to all-cause mortality
1 secondary outcome
Overall Response Rate (ORR)
Time frame: Estimated up to 12 Months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2024.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing RRx-001 + eLOOP Device and Cisplatin/carboplatin plus etoposide in people with Carcinoma, Small Cell Lung, run by EpicentRx, Inc. at 2 sites 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 8 inclusion and 9 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: under way, not looking for participants, as of the sponsor's last update on 31 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Progression Free Survival (PFS) and Overall Survival (OS) (time frame: Estimated up to 12 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Oct 2024.