Clinical Trial 19836

• Overview

  Study Title:

  REPLATINUM: 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

  Summary:

  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

  Objective:

  Primary Objective: To compare the Progression Free Survival (PFS) defined as the time from randomization until disease progression or death between the two arms. Secondary Objectives: To compare ORR (overall response rate, RECIST 1.1) between the two arms. To compare overall survival (OS), defined as the time from randomization to death from any cause between switched-over and non-switched-over patients. Tertiary Objectives: To compare the disease control rate (DCR) defined as the sum of complete responses(CR) + partial responses (PR) + stable disease (SD). To correlate change in circulating tumor cells with response. To compare the Time Without Symptoms and Grade 3-4 Hematologic Toxicity (TWiST)and Quality-Adjusted TWiST (Q-TWiST). To compare platinum sensitization rates between the 2 arms. To compare the percentage of treatment delays and dose reductions. The proportion of patients on the RRx-001 arm that developed pseudoprogression. Exploratory Objectives: To correlate density of TGF-beta 1 receptor in tumor with response. To correlate CD-47 expression on circulating tumor cells (CTCs) with response. To correlate SIRP-alpha expression on circulating monocytes with response. To correlate density of tumor associated macrophages with response. To estimate the proportion of patients on the RRx-001 arm that were treated beyond RECIST 1.1 -defined progressive disease. To compare between the two treatment arms the median time to onset of severe myelosuppression, a composite event comprising Grade 3-4 thrombocytopenia, leukopenia and neutropenia. To compare the hematologic toxicity profile of each arm, which includes percent a. Grade 4 neutropenia b. > Grade 3 anemia c. Grade 4 thrombocytopenia d. Febrile neutropenia e. Platelet transfusions. Safety Objective: To evaluate the safety and tolerability assessed by the frequency and severity of adverse events (AEs), abnormal findings on physical examination, laboratory tests, vital signs,and weight.

• Treatments

  Therapies:

  Chemotherapy (NOS); Immunotherapy

  Medications:

  Paraplatin (carboplatin); RRx-001 (); carboplatin (); cisplatin (); etoposide ()

• Inclusion Criteria

  • Age ≥ 18 and >Prior platinum treatment is required
  • Prior treatment an anti-PD-(L)1 antibody in combination with platinum, unless contraindicated.
  • Patient must have received at least 2 prior lines of therapy
  • Biopsy confirmation of small cell carcinoma lung cancer
  • Capable of providing informed consent and complying with trial procedures
  • Measurable disease by RECIST 1.1. Measurable lesions will be confirmed by imaging (CT scan)
  • ECOG Performance Status 0-2
  • Adequate organ function
  • Prior chemoembolization, radiofrequency ablation, or radiation is allowed as long as the patient has measurable disease and the lesion(s) that is being measured is (1) at least 12 weeks out from palliative therapy and (2) exhibits increased measurable growth
  • Palliative radiotherapy is allowed provided the patient has other sentinel lesions to follow outside of the radiation therapy field(s)
  • Vaccination to COVID-19 is strongly recommended as deemed appropriate by the treating investigator.
  • Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

• Exclusion Criteria

  • Symptomatic central nervous system metastases or neurologically unstable patients that are on increasing steroid dose.
  • The presence of another primary malignancy (excluding in situ of the cervix or basal carcinoma of the skin).
  • Treatment of Small Cell Lung Cancer with any antineoplastic agent with the exception of steroids.
  • 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. NOTE: Patients with history of hepatitis infections controlled with antiviral therapy are allowed.
  • 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)
  • 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
  • Uncontrolled or symptomatic pleural or pericardial effusion
  • Pregnant or nursing. There is a potential for congenital abnormalities and for this regimen to harm nursing infants.
  • Uncontrolled or clinically relevant pulmonary edema
  • Greater than 10% weight loss in the last 6 weeks
  • Any condition that might interfere with participation in this study or in the evaluation of the study results
  • Major surgery within 30 days prior to study day 1

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