RRx-001 Sequentially With a Platinum Doublet or a Platinum Doublet in Third-Line or Beyond in Patients With Small Cell Lung Cancer

Carcinoma, Small Cell Lung Clinical Trial

— REPLATINUM  

Official title:

A Phase 3, Controlled, Open-label, Randomized Study of RRx-001 Administered Sequentially With a Platinum Doublet or a Platinum Doublet in Third-Line or Beyond Small Cell Lung Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03699956
• Other study ID #: RRx001-33
• Status: Terminated
• Phase: Phase 3
• Start date: December 24, 2018
• Est. completion date: March 1, 2024

Study information

• Verified date: March 2024
• Source: EpicentRx, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 cancer.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 18
• Est. completion date: March 1, 2024
• Est. primary completion date: August 11, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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. Maintenance with a checkpoint inhibitor is NOT required

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. PS 0-1

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

Related Conditions & MeSH terms

• Carcinoma, Small Cell
• Carcinoma, Small Cell Lung
• Lung Neoplasms
• Small Cell Lung Carcinoma

Intervention

Combination Product:
• RRx-001 + eLOOP Device
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

Locations

Country	Name	City	State
United States	University of Maryland Marlene and Stewart Greenbaum Comprehensive Cancer Center	Baltimore	Maryland
United States	Rush University Medical Center	Chicago	Illinois
United States	Centura Health Research Center	Denver	Colorado
United States	Millennium Oncology	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Tennessee Cancer Specialists	Knoxville	Tennessee
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Norton Cancer Institute, Norton Healthcare Pavilion	Louisville	Kentucky
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Oncology Hematology West PC dba Nebraska Cancer Specialists	Omaha	Nebraska
United States	Mid Florida Hematology and Oncology Center	Orange City	Florida
United States	AdventHealth Hematology and Oncology	Orlando	Florida
United States	Washington University School of Medicine - Siteman Cancer Center	Saint Louis	Missouri
United States	Utah Cancer Specialist	Salt Lake City	Utah
United States	H. Lee Moffitt Cancer Center & Research Institute, Inc.	Tampa	Florida
United States	Cotton O'Neil Clinical Research Center.Hematology & Oncology	Topeka	Kansas
United States	HOPE Cancer Center of East Texas	Tyler	Texas
United States	The University of Kansas Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
EpicentRx, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival	The time from the date of randomization to disease progression (radiologic and/or symptomatic per RECIST 1.1) or death from any cause	Estimated up to 12 Months
Secondary	Overall Survival	The time from randomization to death from any cause	Estimated up to 12 Months
Secondary	Overall response rate	The proportion of patients with a complete response or a partial response (per RECIST 1.1)	Estimated up to 12 Months