Clinical trial NCT05566041: 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
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Carcinoma, Small Cell Lung
Lead sponsor: EpicentRx, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Sciclone Pharmaceuticals (China) Co., Ltd.
First posted: 2022-10-04
Enrollment: 292
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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).
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 and ≤ 80 years
2. Prior platinum treatment is required
3. Prior treatment with a checkpoint inhibitor is required unless contraindicated.
4. Patient must have received at least 2 prior lines of therapy
5. Biopsy confirmation of small cell lung cancer
6. Capable of providing informed consent and complying with trial procedures
7. Measurable disease by RECIST 1.1. Measurable lesions will be confirmed by imaging (CT scan)
8. Performance Status (ECOG) 0-2

Exclusion Criteria:

1. Symptomatic central nervous system metastases or neurologically unstable patients that are on increasing steroid dose.
2. The presence of another primary malignancy (excluding in situ of the cervix or basal carcinoma of the skin)
3. Treatment of SCLC with any antineoplastic agent with the exception of steroids.
4. 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.
5. 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)
6. 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
7. Uncontrolled or symptomatic pleural or pericardial effusion
8. Pregnant or nursing. There is a potential for congenital abnormalities and for this regimen to harm nursing infants
9. Virologic, serologic, or clinical evidence of active SARS-CoV-2 infection

Primary outcomes:
measure: Progression Free Survival (PFS) and Overall Survival (OS)
timeFrame: Estimated up to 12 Months
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Estimated up to 12 Months
Other outcomes:
measure: Disease Control Rate (DCR)
timeFrame: Estimated up to 12 Months
measure: Relative Dose Intensities (RDIs)
timeFrame: Estimated up to 12 Months
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute, Inc.
state: Florida
city: Westwood
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
Study officials:
References: