RRx-001 + Platinum Chemotherapy for Small Cell Lung Cancer

(REPLATINUM Trial)

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

292 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment called RRx-001 combined with standard chemotherapy on patients with small cell cancer who have not responded to previous treatments. The goal is to see if this combination works better than chemotherapy alone by making the cancer cells more sensitive to the treatment. RRx-001 is an experimental agent designed to help cancer cells respond better to treatment.

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.

What data supports the effectiveness of the drug combination RRx-001 and platinum chemotherapy for small cell lung cancer?

Research shows that the combination of cisplatin and etoposide is effective for treating extensive-stage small-cell lung cancer. Additionally, a study found that RRx-001 followed by platinum and etoposide was effective in patients who had been previously treated for small-cell lung cancer. ^{1 2 3 4 5}

Is the combination of RRx-001 and platinum chemotherapy safe for humans?

The combination of RRx-001 and platinum chemotherapy has been studied in patients with small-cell lung cancer, and the safety profile is generally acceptable. Common side effects include neutropenia (low white blood cell count), mild to moderate esophagitis (inflammation of the esophagus), and mild to moderate radiation pneumonitis (lung inflammation). RRx-001 itself is described as systemically nontoxic in ongoing trials. ^{4 5 6 7 8}

What makes the drug RRx-001 combined with platinum chemotherapy unique for small cell lung cancer?

The drug RRx-001 is unique because it can potentially resensitize small cell lung cancer patients to platinum-based chemotherapy, which is often ineffective after initial treatment. This is achieved through its role as an epigenetic inhibitor, which may help overcome drug resistance and improve treatment outcomes. ^{4 8 9 10 11}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Phase II study of carboplatin and 1-h intravenous etoposide and paclitaxel in a novel sequence as first-line treatment of patients with small-cell lung cancer. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

A phase II study of carboplatin, etoposide, and exisulind in patients with extensive small cell lung cancer: CALGB 30104. [2013]

3. Australia pubmed.ncbi.nlm.nih.gov

Cisplatin plus etoposide versus other platin-based regimens for patients with extensive small-cell lung cancer: a systematic review and meta-analysis of randomised, controlled trials. [2018]

4. England pubmed.ncbi.nlm.nih.gov

RRx-001 followed by platinum plus etoposide in patients with previously treated small-cell lung cancer. [2021]

5. Greece 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. [2022]

6. United States 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. [2017]

7. United States pubmed.ncbi.nlm.nih.gov

Concurrent chemotherapy and radiotherapy for limited small-cell carcinoma of the lung: a Southwest Oncology Group Study. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

RRx-001 in Refractory Small-Cell Lung Carcinoma: A Case Report of a Partial Response after a Third Reintroduction of Platinum Doublets. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Results from a biomarker study to accompany a phase II trial of RRx-001 with reintroduced platinum-based chemotherapy in relapsed small cell carcinoma. [2022]

10. England pubmed.ncbi.nlm.nih.gov

REPLATINUM Phase III randomized study: RRx-001 + platinum doublet versus platinum doublet in third-line small cell lung cancer. [2020]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Partial Response in an RRx-001-Primed Patient with Refractory Small-Cell Lung Cancer after a Third Introduction of Platinum Doublets. [2020]