Clinical Trials /

LB-100, Carboplatin, Etoposide, and Atezolizumab for the Treatment of Untreated Extensive-Stage Small Cell Lung Cancer

NCT04560972

Description:

This phase Ib trial studies the side effects and best dose of LB-100 when given together with carboplatin, etoposide, and atezolizumab for the treatment of untreated extensive-stage small cell lung cancer. 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. LB-100 has been shown to make anticancer drugs (chemotherapy) work better at killing cancer. LB-100 blocks a protein on the surface of cells called PP2A. Blocking this protein makes the tumor cells that express PP2A divide. This allows standard chemotherapy drugs such as carboplatin, etoposide, and atezolizumab work better at killing the tumor cells since these drugs work best at destroying cells that are dividing. Giving LB-100 in combination with standard chemotherapy drugs may work better to treat extensive-stage small cell lung cancer compared to standard chemotherapy drugs alone.

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: LB-100, Carboplatin, Etoposide, and Atezolizumab for the Treatment of Untreated Extensive-Stage Small Cell Lung Cancer
  • Official Title: A Phase Ib Open-Label Study of LB-100 in Combination With Carboplatin/Etoposide/Atezolizumab in Untreated Extensive-Stage Small Cell Lung Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: 20068
  • SECONDARY ID: NCI-2020-04297
  • SECONDARY ID: 20068
  • SECONDARY ID: P30CA033572
  • NCT ID: NCT04560972

Conditions

  • Extensive Stage Lung Small Cell Carcinoma

Interventions

DrugSynonymsArms
AtezolizumabMPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, TecentriqTreatment (LB-100, carboplatin, etoposide, atezolizumab)
CarboplatinBlastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, RibocarboTreatment (LB-100, carboplatin, etoposide, atezolizumab)
EtoposideDemethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16Treatment (LB-100, carboplatin, etoposide, atezolizumab)
Protein Phosphatase 2A Inhibitor LB-100LB-100, PP2A Inhibitor LB-100Treatment (LB-100, carboplatin, etoposide, atezolizumab)

Purpose

This phase Ib trial studies the side effects and best dose of LB-100 when given together with carboplatin, etoposide, and atezolizumab for the treatment of untreated extensive-stage small cell lung cancer. 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. LB-100 has been shown to make anticancer drugs (chemotherapy) work better at killing cancer. LB-100 blocks a protein on the surface of cells called PP2A. Blocking this protein makes the tumor cells that express PP2A divide. This allows standard chemotherapy drugs such as carboplatin, etoposide, and atezolizumab work better at killing the tumor cells since these drugs work best at destroying cells that are dividing. Giving LB-100 in combination with standard chemotherapy drugs may work better to treat extensive-stage small cell lung cancer compared to standard chemotherapy drugs alone.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To determine the recommended phase II dose (RP2D) of protein phosphatase 2A inhibitor
      LB-100 (LB-100) when given in combination with standard carboplatin/etoposide/atezolizumab in
      treatment naive patients with extensive-stage small cell lung cancer (ED-SCLC).

      SECONDARY OBJECTIVES:

      I. To assess objective response rate (ORR). II. To assess progression-free survival (PFS).
      III. To assess overall survival (OS). IV. To assess duration of overall response (DOR). V. To
      assess safety and adverse events (AEs).

      EXPLORATORY OBJECTIVES:

      I. The pharmacokinetics (PK) of LB-100. II. The biomarkers relevant to LB-100 and the disease
      state as well as their correlation to clinical outcomes.

      OUTLINE: This is a dose-escalation study of LB-100.

      INDUCTION: Patients receive LB-100 intravenously (IV) over 15 minutes on days 1 and 3,
      atezolizumab IV over 30-60 minutes on day 1, carboplatin IV over 30-60 minutes on day 1, and
      etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for 4 cycles in the
      absence of disease progression or unacceptable toxicity.

      MAINTENANCE: After completion of induction therapy, patients receive LB-100 IV over 15
      minutes on days 1 and 3 and atezolizumab IV over 30 minutes on day 1. Cycles repeat every 21
      days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed for up to 30 days, and patients
      who discontinue study treatment without disease progression are followed every 6-8 weeks
      thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (LB-100, carboplatin, etoposide, atezolizumab)ExperimentalINDUCTION: Patients receive LB-100 IV over 15 minutes on days 1 and 3, atezolizumab IV over 30-60 minutes on day 1, carboplatin IV over 30-60 minutes on day 1, and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: After completion of induction therapy, patients receive LB-100 IV over 15 minutes on days 1 and 3 and atezolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Atezolizumab
  • Carboplatin
  • Etoposide
  • Protein Phosphatase 2A Inhibitor LB-100

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed extensive-stage disease small cell lung
             carcinoma per the Veterans Administration Lung Study Group (VALG) staging system

          -  Measurable disease as defined by Response Evaluation Criteria in Solid Tumors
             (RECIST): Revised RECIST guideline (version 1.1)

          -  Estimated life expectancy of at least 12 weeks

          -  For women: Must be surgically sterile (surgical procedure: bilateral tubal ligation),
             post-menopausal (at least 12 consecutive months of amenorrhea) or have a negative
             pregnancy test. Women of childbearing potential must be compliant with a medically
             approved contraceptive regimen (intrauterine device [IUD], birth control pills, or
             barrier device) during and for 3 months after the treatment period; must have a
             negative serum or urine pregnancy test within 14 days before study drug treatment and
             must not be breastfeeding

          -  For men: agreement to remain abstinent or use medically approved contraceptive
             measures, as defined below:

               -  With female partners of childbearing potential or pregnant female partners, men
                  must remain abstinent or use a condom during study therapy and for at least 6
                  months after the last dose of study therapy to avoid exposing the embryo

          -  A performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) scale

          -  Absolute neutrophil (segmented and bands) count (ANC) >= 1.5 x 10/L

          -  Platelets >= 100 x 10/L

          -  Hemoglobin >= 9 g/dL

          -  Bilirubin =< 1.5 times upper limits of normal (ULN) may be enrolled

          -  Alkaline phosphatase (AP), alanine aminotransferase (ALT) and aspartate
             aminotransferase (AST) =< 3.0 times ULN (AP, AST, and ALT =< 5 times ULN are
             acceptable if the liver has tumor involvement)

          -  Calculated creatinine clearance (CrCl) >= 45 mL/min based on the Cockcroft and Gault
             formula

          -  All subjects must have the ability to understand and the willingness to sign a written
             informed consent

          -  No prior systemic chemotherapy, immunotherapy, biological, hormonal, or
             investigational therapy for SCLC

        Exclusion Criteria:

          -  Currently enrolled in, or discontinued within the last 30 days from, a clinical trial
             involving an investigational product or non-approved use of a drug or device, or
             concurrently enrolled in any other type of medical research judged not to be
             scientifically or medically compatible with this study

          -  Diagnosis of non-small cell lung cancer (NSCLC) or mixed NSCLC and small cell lung
             cancer (SCLC)

          -  No prior malignancy other than SCLC, carcinoma in situ of the cervix, or nonmelanoma
             skin cancer, unless that prior malignancy was diagnosed and definitively treated 5 or
             more years prior to study entry with no subsequent evidence of recurrence. Patients
             with a history of low grade (Gleason score =< 6 = Gleason group 1) localized prostate
             cancer will be eligible even if diagnosed less than 5 years prior to study entry

          -  Serious concomitant systemic disorder that, in the opinion of the investigator, would
             compromise the patient's ability to adhere to the protocol

          -  Active or ongoing infection during screening requiring the use of systemic antibiotics

          -  Serious cardiac condition, such as myocardial infarction within 6 months, angina, or
             heart disease as defined by the New York Heart Association class III or IV

          -  Clinical evidence of central nervous system (CNS) metastases or leptomeningeal
             carcinomatosis, except for individuals who have previously-treated CNS metastases, are
             asymptomatic, and have had no requirement for steroid medication for 1 week prior to
             the first dose of study drug and have completed radiation 2 weeks prior to the first
             dose of study drug

          -  Known or suspected allergy to any agent given in association with this trial

          -  Pregnant or lactating women

          -  History of autoimmune disease, including minor/mild autoimmune disease not requiring
             immunosuppressants (such as eczema on less than 10% of the body surface area and long
             term diabetes mellitus type 1 on stable insulin)

          -  Active, known hepatitis B or hepatitis C

          -  Human immunodeficiency virus (HIV) positive

          -  Treatment with systemic corticosteroid or other immunosuppressive medication. The use
             of inhaled corticosteroids for chronic obstructive pulmonary disease,
             mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension,
             and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed

          -  Administration of a live, attenuated vaccine within 28 days prior to study

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
             drainage procedures (once monthly or more frequently). Patients with indwelling
             catheters are allowed

          -  Uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or calcium >
             12 mg/dL or corrected serum calcium > ULN). Patients who are receiving denosumab prior
             to study entry must be willing and eligible to discontinue its use and replace it with
             a bisphosphonate while in the study

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
             obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active
             pneumonitis on screening chest computed tomography (CT) scan. History of radiation
             pneumonitis in the radiation field (fibrosis) is permitted

          -  Prior allogeneic bone marrow transplantation or solid organ transplant

          -  Subjects, who in the opinion of the investigator, may not be able to comply with the
             safety monitoring requirements of the study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended phase II dose (RP2D)
Time Frame:End of first cycle (21 days)
Safety Issue:
Description:Measured using dose-limiting toxicity (DLT) during the first cycle as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description:Measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Patients who respond to treatment and die without progressive disease (PD) (including death from study disease), duration of response will be censored at the date of the last objective progression-free disease assessment. For responding patients not known to have died as of the data cut-off date and who do not have PD, duration of response will be censored at the last progression-free assessment date. For responding patients who receive subsequent anticancer therapy (after discontinuation from all study treatment excluding PCI) prior to disease progression, duration of response will be censored at the date of last progression-free assessment prior to the initiation of post discontinuation anticancer therapy.
Measure:Duration of overall response
Time Frame:Up to 2 years
Safety Issue:
Description:Measured by RECIST v1.1.
Measure:Incidence of safety and adverse events
Time Frame:Up to 2 years
Safety Issue:
Description:Assessed by CTCAE version 5.0.
Measure:Progression-free survival (PFS)
Time Frame:Up to 2 years
Safety Issue:
Description:As defined by RECIST v1.1.
Measure:Overall survival (OS)
Time Frame:Time from the date of study enrollment to the date of death from any cause, assessed up to 2 years
Safety Issue:
Description:OS which is defined as the time from the date of study enrollment to the date of death from any cause. For patients who are still alive as of the data cutoff date, OS time will be censored on the date of the patient's last contact (last contact for patients in post discontinuation is last known alive date in mortality status).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:City of Hope Medical Center

Last Updated

September 17, 2020