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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03699956
Recruitment Status : Active, not recruiting
First Posted : October 9, 2018
Last Update Posted : April 10, 2020
Sponsor:
Information provided by (Responsible Party):
EpicentRx, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
Carcinoma, Small Cell Lung Combination Product: RRx-001 + eLOOP Device Drug: Cisplatin/carboplatin plus etoposide Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 126 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
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).
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 24, 2018
Estimated Primary Completion Date : November 1, 2020
Estimated Study Completion Date : May 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 1

RRx-001 + eLOOP Device 4 mg IV infusion once weekly for 3 weeks

Cisplatin/carboplatin plus etoposide (up to 4 cycles):

  1. Cisplatin or Carboplatin:

    1. Cisplatin initially dosed at 60 mg/m2 on Day 1 every 3 weeks OR
    2. Carboplatin initially dosed at an AUC (area under the curve) of 5 on Day 1 every 3 weeks
  2. Etoposide to be given per the initial approval by the package insert (USPI FDA) at 100 mg/m2 Days 1-3 every 3 weeks
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

Active Comparator: Arm 2

Cisplatin/carboplatin plus etoposide (up to 4 cycles):

  1. Cisplatin or Carboplatin:

    1. Cisplatin initially dosed at 60 mg/m2 on Day 1 every 3 weeks OR
    2. Carboplatin initially dosed at an AUC of 5 on Day 1 every 3 weeks
  2. Etoposide to be given per the initial approval by the package insert (USPI FDA) at 100 mg/m2 Days 1-3 every 3 weeks
Drug: Cisplatin/carboplatin plus etoposide
Standard of care platinum doublet chemotherapy




Primary Outcome Measures :
  1. Progression Free Survival [ Time Frame: Estimated up to 12 Months ]
    The time from the date of randomization to disease progression (radiologic and/or symptomatic per RECIST 1.1) or death from any cause


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: Estimated up to 12 Months ]
    The time from randomization to death from any cause

  2. Overall response rate [ Time Frame: Estimated up to 12 Months ]
    The proportion of patients with a complete response or a partial response (per RECIST 1.1)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03699956


Locations
Show Show 18 study locations
Sponsors and Collaborators
EpicentRx, Inc.
Investigators
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Study Director: Bryan Oronsky, MD, PhD EpicentRx, Inc.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: EpicentRx, Inc.
ClinicalTrials.gov Identifier: NCT03699956    
Other Study ID Numbers: RRx001-33
First Posted: October 9, 2018    Key Record Dates
Last Update Posted: April 10, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by EpicentRx, Inc.:
RRx-001
Lung Cancer
Lung Neoplasms
Phase 3
Immunotherapy
Small Cell Carcinoma
Additional relevant MeSH terms:
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Lung Neoplasms
Small Cell Lung Carcinoma
Carcinoma, Small Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carboplatin
Etoposide
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action