Clinical Trials /

Lamivudine in Combination With Chemoimmunotherapy for the Treatment of Extensive Stage Small Cell Lung Cancer

NCT04696575

Description:

This phase II trial studies the effect of lamivudine in combination with standard of care chemoimmunotherapy in treating patients with extensive stage small cell lung cancer. Even though small cell lung cancer is initially highly responsive to first-line chemotherapy treatment, treatment resistance inevitably emerges; treatment resistance is when tumor cells stop responding to a drug treatment that they had previously responded to. Lamivudine is an oral antiviral a drug that may be able to reduce the ability of tumors to develop drug resistance. Chemotherapy drugs, such as carboplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving lamivudine together with the usual standard of care chemoimmunotherapy may help prevent the growth and spread of the tumor cells to other parts of the body.

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Lamivudine in Combination With Chemoimmunotherapy for the Treatment of Extensive Stage Small Cell Lung Cancer
  • Official Title: A Phase II Trial of Lamivudine in Combination With Chemoimmunotherapy in Patients With Extensive Stage SCLC

Clinical Trial IDs

  • ORG STUDY ID: I 691720
  • SECONDARY ID: NCI-2020-13169
  • SECONDARY ID: I 691720
  • NCT ID: NCT04696575

Conditions

  • Extensive Stage Lung Small Cell Carcinoma

Interventions

DrugSynonymsArms
AtezolizumabMPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, TecentriqTreatment (lamivudine, chemoimmunotherapy)
CarboplatinBlastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, RibocarboTreatment (lamivudine, chemoimmunotherapy)
EtoposideDemethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16Treatment (lamivudine, chemoimmunotherapy)
Lamivudine(-)-BCH-189, 3TC, Epivir, GR109714X, LAMTreatment (lamivudine, chemoimmunotherapy)

Purpose

This phase II trial studies the effect of lamivudine in combination with standard of care chemoimmunotherapy in treating patients with extensive stage small cell lung cancer. Even though small cell lung cancer is initially highly responsive to first-line chemotherapy treatment, treatment resistance inevitably emerges; treatment resistance is when tumor cells stop responding to a drug treatment that they had previously responded to. Lamivudine is an oral antiviral a drug that may be able to reduce the ability of tumors to develop drug resistance. Chemotherapy drugs, such as carboplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving lamivudine together with the usual standard of care chemoimmunotherapy may help prevent the growth and spread of the tumor cells to other parts of the body.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To evaluate the 6-month progression-free survival (PFS) rate of lamivudine in combination
      with platinum-based chemotherapy in patients with extensive stage small cell lung cancer
      (SCLC).

      SECONDARY OBJECTIVES:

      I. To evaluate the 12-month survival and overall survival (OS) of patients with extensive
      stage SCLC receiving study treatment.

      II. To assess the toxicity of the combination of lamivudine with platinum-based chemotherapy
      in this population.

      EXPLORATORY OBJECTIVE:

      I. To study tissue and blood-based biomarkers as potential predictors of treatment efficacy.

      OUTLINE:

      INDUCTION: Patients receive lamivudine orally (PO) once daily (QD) on days 1-28. Patients
      also receive carboplatin intravenously (IV) over 30-60 minutes and atezolizumab IV on day 1,
      and etoposide IV over 60-120 minutes on days 1-3. Treatment repeats every 28 days for up to 4
      cycles in the absence of disease progression or unacceptable toxicity.

      MAINTENANCE: Patients receive lamivudine PO QD on days 1-28 and atezolizumab IV on day 1.
      Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

      NOTE: Patients who are not eligible for atezolizumab as outlined in exclusion criteria or who
      refuse to receive atezolizumab may still be treated in this study with carboplatin and
      etoposide as the IV drug component, in addition to lamivudine orally administered.

      After completion of study treatment, patients are followed up for 30 days and then every 60
      days thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (lamivudine, chemoimmunotherapy)ExperimentalINDUCTION: Patients receive lamivudine PO QD on days 1-28. Patients also receive carboplatin IV over 30-60 minutes and atezolizumab IV on day 1, and etoposide IV over 60-120 minutes on days 1-3. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive lamivudine PO QD on days 1-28 and atezolizumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. NOTE: Patients who are not eligible for atezolizumab as outlined in exclusion criteria or who refuse to receive atezolizumab may still be treated in this study with carboplatin and etoposide as the IV drug component, in addition to lamivudine orally administered.
  • Atezolizumab
  • Carboplatin
  • Etoposide
  • Lamivudine

Eligibility Criteria

        Inclusion Criteria:

          -  Age >= 18 years of age

          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 1 at the
             time of study treatment initiation

          -  Histologically or cytologically confirmed diagnosis of SCLC

          -  Patient should have extensive stage disease, defined as, malignant pleural effusion,
             pulmonary metastases in a different lobe in the ipsilateral lung or contralateral
             lung, and/or the presence of extra-thoracic metastatic disease

          -  Must have measurable disease based on Response Evaluation Criteria in Solid Tumors
             (RECIST) 1.1 prior to starting platinum-based systemic chemotherapy

          -  Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

          -  Platelets >= 100 x 10^9/L

          -  Hemoglobin >= 9 g/dL

          -  Serum creatinine =< 1.5 x institution upper limit of normal (ULN) and calculated
             creatinine clearance of at least 15 ml/min

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x upper limit
             of normal (ULN) (ALT and AST =< 5 x ULN is acceptable if liver metastases are present)

          -  Total serum bilirubin =< 1.5 x ULN. For patients with well documented Gilbert's
             syndrome, total bilirubin =< 3 x ULN with direct bilirubin within normal range

          -  Patients may receive no more than 1 cycle of standard chemotherapy or
             chemoimmunotherapy for their current diagnosis prior to study treatment

          -  Patients with prior treatment for small cell lung cancer will be eligible if either of
             the following conditions are met:

               -  Received no more than one-line of platinum-based chemotherapy for small cell lung
                  cancer, or

               -  Received >= 3 cycles of platinum-based chemotherapy for SCLC previously, with the
                  last platinum-based treatment administered >= 12 months prior to diagnosis of
                  recurrence/relapse in addition to not having experienced disease progression
                  while receiving prior platinum-based treatment for SCLC

          -  Participants of child-bearing potential must agree to use adequate contraceptive
             methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study
             entry. Should a woman become pregnant or suspect she is pregnant while she or her
             partner is participating in this study, she should inform her treating physician
             immediately

          -  Participant or legal representative must understand the investigational nature of this
             study and sign an approved written informed consent form prior to receiving any study
             related procedure

        Exclusion Criteria:

          -  Receipt of anticancer chemotherapy/chemoimmunotherapy within 4 weeks prior to the
             first administration of study drug other than what is allowed in the inclusion
             criteria

          -  Symptomatic brain metastasis

               -  Patients with treated brain metastases are eligible provided they have recovered
                  from effects of radiation and neurological symptoms are improved or controlled
                  for at least two weeks prior to enrollment

               -  Patients with asymptomatic brain metastases who are being treated with systemic
                  chemotherapy alone are also eligible if no more than 6 lesions each less than 1
                  cm in size is present at the time of initiating protocol treatment

          -  Leptomeningeal involvement regardless of treatment status

          -  Participation in another interventional study within the last 28 days of study
             enrollment

          -  Had major surgery within 14 days prior to starting study drug or has not recovered
             from major side effects (tumor biopsy is not considered major surgery) resulting from
             a prior surgery

          -  Positive for immunosuppressive disease, acquired immunodeficiency syndrome (AIDS) or
             other immune depressing diseases. For human immunodeficiency virus (HIV), HVC and
             HBC-mandatory testing is required prior to enrollment

               -  Note: Patients with past or resolved hepatitis B virus (HBV) infection (defined
                  as the presence of hepatitis B surface antibody [HBsAb] and absence of hepatitis
                  B surface antigen [HBsAg]) are eligible (HBV deoxyribonucleic acid [DNA] should
                  be obtained in patients if only anti-hepatitis B core [HBc] antibody was present
                  prior to randomization). Patients with active/untreated hepatitis C virus (HCV)
                  will be excluded from the study; patients who test positive for HCV antibody are
                  eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic
                  acid (RNA)

          -  Active, clinically serious infections or other serious uncontrolled medical
             conditions, including chronic viral hepatitis (testing for hepatitis B, C required)

          -  Patient has known hypersensitivity to the components of the study drugs or any analogs

          -  History or current evidence of any condition, therapy, or laboratory abnormality that
             might confound the results of the study, interfere with the patient's participation
             for the full duration of the study, or is not in the best interest of the patient to
             participate, in the opinion of the treating Investigator, including, but not limited
             to:

               -  Myocardial infarction or arterial or venous thromboembolic events within 6 months
                  prior to baseline or severe or unstable angina, New York Heart Association (NYHA)
                  class III or IV disease

               -  History of documented congestive heart failure (New York Heart Association
                  functional classification III or IV) within 6 months prior to baseline

               -  Poorly controlled arrhythmias

          -  Contraindications to atezolizumab: Patients with active autoimmune disorder or prior
             history of autoimmune disorder requiring immunosuppressive agents within preceding two
             years will not be allowed to receive atezolizumab but will be able to receive the
             other drugs included in the treatment regimen, if eligible
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival
Time Frame:From the date of registration to the date of first confirmed progression or death, whichever occurred first, assessed at 6 months
Safety Issue:
Description:The primary test of efficacy will be carried out using an exact binomial test of a proportion. Descriptive analyses will be carried out using the Kaplan-Meier product-limit estimator. Patients who are treated beyond RECIST progression and subsequently had tumor response while on study (and no other intervening treatment) will be classified as pseudoprogression and not counted as progression event.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:From registration to death from any cause or 5 years from time of enrollment, whichever occurs first
Safety Issue:
Description:Descriptive analyses will be carried out using the Kaplan-Meier product-limit estimator.
Measure:Incidence of toxicities
Time Frame:Up to 30 days after the end of all treatment
Safety Issue:
Description:Per National Cancer Institute Common Terminology Criteria for Adverse Events version 5, the term toxicity is defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment. The maximum grade for each type of toxicity will be recorded for each patient and will be used for reporting. Frequency tables will be reviewed to determine toxicity patterns. In addition, all adverse event data graded as 3, 4, or 5 and classified as either "unrelated or unlikely to be related" to study treatment in the event of an actual relationship developing will be reviewed.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Roswell Park Cancer Institute

Last Updated

March 4, 2021