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

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ClinicalTrials.gov Identifier: NCT04560972
Recruitment Status : Recruiting
First Posted : September 23, 2020
Last Update Posted : March 15, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

Tracking Information
First Submitted Date  ICMJE June 22, 2020
First Posted Date  ICMJE September 23, 2020
Last Update Posted Date March 15, 2021
Estimated Study Start Date  ICMJE March 31, 2021
Estimated Primary Completion Date August 8, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 17, 2020)
Recommended phase II dose (RP2D) [ Time Frame: End of first cycle (21 days) ]
Measured using dose-limiting toxicity (DLT) during the first cycle as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2020)
  • Objective response rate (ORR) [ Time Frame: Up to 2 years ]
    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.
  • Duration of overall response [ Time Frame: Up to 2 years ]
    Measured by RECIST v1.1.
  • Incidence of safety and adverse events [ Time Frame: Up to 2 years ]
    Assessed by CTCAE version 5.0.
  • Progression-free survival (PFS) [ Time Frame: Up to 2 years ]
    As defined by RECIST v1.1.
  • 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 ]
    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).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 17, 2020)
  • Cmax of LB-100 [ Time Frame: Cycle 1 day 1: Pre-dose, immediately post LB-100 infusion, at 15 & 30 minutes, at 1, 2, 4, and 8 hours post LB-100 infusion (Each cycle is 21 days); Cycle 1, days 2-3: Pre-dose and 24 hours post LB-100 infusion (Each cycle is 21 days) ]
    Plasma sampling for pharmacokinetic (PK) measurements of LB-100 will be performed . Blood samples will be collected to determine the Cmax of LB-100.
  • Cmax of endothall [ Time Frame: Cycle 1 day 1: Pre-dose, immediately post LB-100 infusion, at 15 & 30 minutes, at 1, 2, 4, and 8 hours post LB-100 infusion (Each cycle is 21 days); Cycle 1, days 2-3: Pre-dose and 24 hours post LB-100 infusion (Each cycle is 21 days) ]
    Plasma sampling for pharmacokinetic (PK) measurements of endothall, the metabolite of LB-100, will be performed . Blood samples will be collected to determine the Cmax of endothall.
  • Tmax of LB-100 [ Time Frame: Cycle 1 day 1: Pre-dose, immediately post LB-100 infusion, at 15 & 30 minutes, at 1, 2, 4, and 8 hours post LB-100 infusion (Each cycle is 21 days); Cycle 1, days 2-3: Pre-dose and 24 hours post LB-100 infusion (Each cycle is 21 days) ]
    Plasma sampling for pharmacokinetic (PK) measurements of LB-100 will be performed . Blood samples will be collected to determine the Tmax of LB-100.
  • Tmax of endothall [ Time Frame: Cycle 1 day 1: Pre-dose, immediately post LB-100 infusion, at 15 & 30 minutes, at 1, 2, 4, and 8 hours post LB-100 infusion (Each cycle is 21 days); Cycle 1, days 2-3: Pre-dose and 24 hours post LB-100 infusion (Each cycle is 21 days) ]
    Plasma sampling for pharmacokinetic (PK) measurements of endothall, the metabolite of LB-100, will be performed . Blood samples will be collected to determine the Tmax of endothall.
  • t1/2 of LB-100 [ Time Frame: Cycle 1 day 1: Pre-dose, immediately post LB-100 infusion, at 15 & 30 minutes, at 1, 2, 4, and 8 hours post LB-100 infusion (Each cycle is 21 days); Cycle 1, days 2-3: Pre-dose and 24 hours post LB-100 infusion (Each cycle is 21 days) ]
    Plasma sampling for pharmacokinetic (PK) measurements of LB-100 will be performed . Blood samples will be collected to determine the t1/2 of LB-100.
  • t1/2 of endothall [ Time Frame: Cycle 1 day 1: Pre-dose, immediately post LB-100 infusion, at 15 & 30 minutes, at 1, 2, 4, and 8 hours post LB-100 infusion (Each cycle is 21 days); Cycle 1, days 2-3: Pre-dose and 24 hours post LB-100 infusion (Each cycle is 21 days) ]
    Plasma sampling for pharmacokinetic (PK) measurements of endothall, the metabolite of LB-100, will be performed . Blood samples will be collected to determine the t1/2 of endothall.
  • AUC0-t of LB-100 [ Time Frame: Cycle 1 day 1: Pre-dose, immediately post LB-100 infusion, at 15 & 30 minutes, at 1, 2, 4, and 8 hours post LB-100 infusion (Each cycle is 21 days); Cycle 1, days 2-3: Pre-dose and 24 hours post LB-100 infusion (Each cycle is 21 days) ]
    Plasma sampling for pharmacokinetic (PK) measurements of LB-100 will be performed . Blood samples will be collected to determine the AUC0-t of LB-100.
  • AUC0-t of endothall [ Time Frame: Cycle 1 day 1: Pre-dose, immediately post LB-100 infusion, at 15 & 30 minutes, at 1, 2, 4, and 8 hours post LB-100 infusion (Each cycle is 21 days); Cycle 1, days 2-3: Pre-dose and 24 hours post LB-100 infusion (Each cycle is 21 days) ]
    Plasma sampling for pharmacokinetic (PK) measurements of endothall, the metabolite of LB-100, will be performed . Blood samples will be collected to determine the AUC0-t of endothall.
  • CL of LB-100 [ Time Frame: Cycle 1 day 1: Pre-dose, immediately post LB-100 infusion, at 15 & 30 minutes, at 1, 2, 4, and 8 hours post LB-100 infusion (Each cycle is 21 days); Cycle 1, days 2-3: Pre-dose and 24 hours post LB-100 infusion (Each cycle is 21 days) ]
    Plasma sampling for pharmacokinetic (PK) measurements of LB-100 will be performed . Blood samples will be collected to determine the CL of LB-100.
  • CL of endothall [ Time Frame: Cycle 1 day 1: Pre-dose, immediately post LB-100 infusion, at 15 & 30 minutes, at 1, 2, 4, and 8 hours post LB-100 infusion (Each cycle is 21 days); Cycle 1, days 2-3: Pre-dose and 24 hours post LB-100 infusion (Each cycle is 21 days) ]
    Plasma sampling for pharmacokinetic (PK) measurements of endothall, the metabolite of LB-100, will be performed . Blood samples will be collected to determine the CL of endothall.
  • Relative abundance of immune cell populations [ Time Frame: Up to 2 years ]
    The signaling states that evolve in immune cells during treatment and that differentiate responders from non-responders. Number of effector memory T cells Number of classical monocytes
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE LB-100, Carboplatin, Etoposide, and Atezolizumab for the Treatment of Untreated Extensive-Stage Small Cell Lung Cancer
Official Title  ICMJE A Phase Ib Open-Label Study of LB-100 in Combination With Carboplatin/Etoposide/Atezolizumab in Untreated Extensive-Stage Small Cell Lung Carcinoma
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Extensive Stage Lung Small Cell Carcinoma
Intervention  ICMJE
  • Drug: Atezolizumab
    Given IV
    Other Names:
    • MPDL 3280A
    • MPDL 328OA
    • MPDL-3280A
    • MPDL3280A
    • MPDL328OA
    • RG7446
    • RO5541267
    • Tecentriq
  • Drug: Carboplatin
    Given IV
    Other Names:
    • Blastocarb
    • Carboplat
    • Carboplatin Hexal
    • Carboplatino
    • Carboplatinum
    • Carbosin
    • Carbosol
    • Carbotec
    • CBDCA
    • Displata
    • Ercar
    • JM-8
    • Nealorin
    • Novoplatinum
    • Paraplatin
    • Paraplatin AQ
    • Paraplatine
    • Platinwas
    • Ribocarbo
  • Drug: Etoposide
    Given IV
    Other Names:
    • Demethyl Epipodophyllotoxin Ethylidine Glucoside
    • EPEG
    • Lastet
    • Toposar
    • Vepesid
    • VP 16
    • VP 16-213
    • VP-16
    • VP-16-213
    • VP16
  • Drug: Protein Phosphatase 2A Inhibitor LB-100
    Given IV
    Other Names:
    • LB-100
    • PP2A Inhibitor LB-100
Study Arms  ICMJE Experimental: Treatment (LB-100, carboplatin, etoposide, atezolizumab)

INDUCTION: 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.

Interventions:
  • Drug: Atezolizumab
  • Drug: Carboplatin
  • Drug: Etoposide
  • Drug: Protein Phosphatase 2A Inhibitor LB-100
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 17, 2020)
18
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 8, 2022
Estimated Primary Completion Date August 8, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04560972
Other Study ID Numbers  ICMJE 20068
NCI-2020-04297 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
20068 ( Other Identifier: City of Hope Medical Center )
P30CA033572 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party City of Hope Medical Center
Study Sponsor  ICMJE City of Hope Medical Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Ravi Salgia City of Hope Medical Center
PRS Account City of Hope Medical Center
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP