RRx-001 + Platinum Chemotherapy for Small Cell Lung Cancer

(REPLATINUM Trial)

Not currently recruiting at 5 trial locations

Overseen By Scott Caroen

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: EpicentRx, Inc.

Must be taking: Platinum chemotherapy

Must not be taking: Antineoplastic agents

Disqualifiers: CNS metastases, Other malignancy, Uncontrolled illnesses, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding RRx-001, an experimental treatment, to platinum chemotherapy is more effective than chemotherapy alone for small cell lung cancer. It targets individuals who have tried at least two other treatments, including a platinum-based one, and still have measurable cancer. Those with small cell lung cancer who have undergone two or more previous treatments might find this trial suitable. As a Phase 3 trial, it represents the final step before FDA approval, providing an opportunity to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it excludes patients on certain treatments, so it's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found RRx-001 to be safe for patients. The most common side effects included mild discomfort at the infusion site (experienced by 23% of patients) and reduced appetite (reported by 15.3% of patients). Research has shown that combining RRx-001 with chemotherapy drugs like platinum and etoposide is feasible and shows promising results, indicating the combination can be used safely in treatment.

Cisplatin, carboplatin, and etoposide are common chemotherapy drugs. They are generally effective but can cause typical side effects like nausea, tiredness, and low blood cell counts. These side effects are well-known and managed in medical settings.

Overall, evidence suggests that RRx-001, when used with standard chemotherapy, is safe and has manageable side effects similar to other chemotherapy treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for small cell lung cancer?

Unlike the standard treatments for small cell lung cancer, which typically include platinum-based chemotherapy drugs like cisplatin or carboplatin combined with etoposide, the investigational treatment RRx-001 introduces a novel approach. RRx-001 works by targeting cancer cells through a unique mechanism that involves modulating the tumor microenvironment and enhancing the effects of chemotherapy. This could potentially improve the effectiveness of existing chemotherapy regimens. Additionally, RRx-001 is administered with an innovative eLOOP device, which may optimize drug delivery and reduce side effects. Researchers are excited about RRx-001 because it represents a fresh angle in combating small cell lung cancer, potentially improving patient outcomes and quality of life.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer?

Research has shown that RRx-001, when combined with platinum chemotherapy, yields promising results for small cell lung cancer. In this trial, one group of participants will receive RRx-001 with platinum chemotherapy and etoposide. Earlier studies indicated that patients who received RRx-001 before platinum chemotherapy responded well, suggesting this combination might outperform chemotherapy alone. One case study reported a partial improvement in a patient using this treatment, highlighting its potential in challenging cases. Although the treatment remains under investigation, these early findings suggest that RRx-001 could enhance the effectiveness of standard chemotherapy for small cell lung cancer. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with small cell lung cancer who've had at least two prior treatments, including platinum chemotherapy and a checkpoint inhibitor (unless not suitable). They must have measurable disease confirmed by CT scan, be able to consent and follow the study plan. Exclusions include uncontrolled illnesses, certain infections like Hepatitis B/C or COVID-19, allergic reactions to platinum drugs (except blood toxicity), symptomatic brain metastases, another primary cancer, pregnancy/nursing.

Inclusion Criteria

My cancer can be measured and tracked using scans.

My lung cancer was confirmed by a biopsy.

I have previously been treated with a checkpoint inhibitor, unless it was not suitable for me.

Exclusion Criteria

I have fluid buildup in my chest or heart area that is causing symptoms.

I don't have any health conditions that would make the study medication unsafe for me.

I have brain metastases causing symptoms or need more steroids to manage them.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive RRx-001 + platinum doublet or platinum doublet alone for up to 4 cycles

12 weeks

Weekly visits for RRx-001 infusion, every 3 weeks for chemotherapy

Crossover

Participants in Arm 2 may cross over to receive RRx-001 + platinum doublet if their cancer progresses

Until disease progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

Estimated up to 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin/Carboplatin
• Etoposide
• RRx-001

Trial Overview The study compares RRx-001 combined with a platinum-based chemo drug using an eLOOP Device against standard treatment of cisplatin/carboplatin plus etoposide in patients who are receiving their third line or later treatment for small cell lung cancer. The goal is to see if adding RRx-001 improves effectiveness.

How Is the Trial Designed?

Group I: Arm 1 Experimental Treatment 1 Intervention

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

Group II: Arm 2 Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

EpicentRx, Inc.

Lead Sponsor

Trials

16

Recruited

1,000+

Sciclone Pharmaceuticals (China) Co., Ltd.

Collaborator

Trials

1

Recruited

290+

Published Research Related to This Trial

In a pilot phase II trial involving 31 high-risk patients with advanced non-small cell lung cancer (NSCLC), a novel metronomic regimen of weekly cisplatin and oral etoposide showed a promising objective response rate of 45.2%, indicating significant anti-tumor activity.

The treatment was generally well tolerated, although some patients experienced severe side effects like leukopenia and anemia, and three patients died from pulmonary embolism; however, the regimen demonstrated a mean survival time of 13 months, suggesting potential benefits even for patients with poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel metronomic chemotherapy regimen of weekly platinum and daily oral etoposide in high-risk non-small cell lung cancer patients. Correale, P., Cerretani, D., Remondo, C., et al.[2022]

In a trial involving 228 patients with advanced non-small-cell lung cancer, cisplatin (CDDP) combined with etoposide showed a higher objective response rate (27%) compared to carboplatin (CBDCA) with etoposide (16%), although this difference was not statistically significant (P = .07).

Cisplatin treatment was associated with significantly increased toxicity, particularly myelosuppression and renal function impairment, indicating that while it may be more effective, it also poses greater risks compared to carboplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organization for Research and Treatment of Cancer Protocol 07861. Klastersky, J., Sculier, JP., Lacroix, H., et al.[2017]

In a pilot study of 40 patients with limited-stage small-cell lung carcinoma, concurrent chemotherapy with cisplatin and etoposide alongside radiotherapy resulted in a high complete response rate, with 23 patients showing complete remission.

The median survival for all patients was 18 months, and five patients survived over 2 years without therapy, indicating promising long-term outcomes and acceptable toxicity levels, primarily neutropenia and mild to moderate radiation-related effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemotherapy and radiotherapy for limited small-cell carcinoma of the lung: a Southwest Oncology Group Study. McCracken, JD., Janaki, LM., Taylor, SB., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03699956

Study Details: RRx-001 With Platinum Doublet in SCLC This 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 ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.e20104

Multicenter phase II trial of RRx-001 in previously treated ... The most common treatment-emergent adverse events from RRx-001 was mild discomfort at the infusion site (23%) and decreased appetite (15.3%).

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4821137/

RRx-001 in Refractory Small-Cell Lung Carcinoma: A Case ... The purpose of this case study is first to report a partial response to carboplatin and etoposide in a patient with small-cell lung cancer pretreated with RRx- ...

4. nature.com nature.com/articles/s41416-019-0504-8

RRx-001 + Platinum etoposide for treated SCLC RRx-001 followed by re-challenge with platinum plus etoposide chemotherapy is feasible and associated with promising results.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05566041?spons=COVERAGE%5BFullMatch%5DEXPANSION%5BNone%5D(%22EpicentRx,%20Inc.%22)&viewType=Table&rank=2

Study Details | NCT05566041 | A Phase 3, Controlled, ... 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 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31231122/

RRx-001 followed by platinum plus etoposide in patients ... RRx-001 followed by re-challenge with platinum plus etoposide chemotherapy is feasible and associated with promising results.