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Testing Maintenance Therapy for Small Cell Lung Cancer in Patients With SLFN11 Positive Biomarker

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ClinicalTrials.gov Identifier: NCT04334941
Recruitment Status : Recruiting
First Posted : April 6, 2020
Last Update Posted : June 15, 2021
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE April 3, 2020
First Posted Date  ICMJE April 6, 2020
Last Update Posted Date June 15, 2021
Actual Study Start Date  ICMJE June 15, 2020
Estimated Primary Completion Date November 30, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 3, 2020)
Progression free survival [ Time Frame: From the date of maintenance randomization to the date of first document of progression or symptomatic deterioration, or death due to any cause, assessed up to 18 months ]
Analysis will be done using a 1-sided 10% level stratified log-rank test. Will be estimated using the Kaplan-Meier method. Associated confidence intervals around the median will be performed using the Brookmeyer-Crowley method.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 3, 2020)
Overall survival [ Time Frame: From the date of maintenance randomization until death from any cause, with participants last known to be alive censored at the date of last contact, assessed up to 3 years from randomization ]
Will be estimated using the Kaplan-Meier method. Associated confidence intervals around the median will be performed using the Brookmeyer-Crowley method.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Testing Maintenance Therapy for Small Cell Lung Cancer in Patients With SLFN11 Positive Biomarker
Official Title  ICMJE Phase II Randomized Study of Maintenance Atezolizumab Versus Atezolizumab in Combination With Talazoparib in Patients With SLFN11 Positive Extensive Stage Small Cell Lung Cancer (ES-SCLC)
Brief Summary This phase II trial studies whether atezolizumab in combination with talazoparib works better than atezolizumab alone as maintenance therapy for patients with SLFN11-positive extensive-stage small cell lung cancer. 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. PARPs are proteins that help repair damage to DNA, the genetic material that serves as the body's instruction book. Changes (mutations) in DNA can cause tumor cells to grow quickly and out of control, but PARP inhibitors like talazoparib may keep PARP from working, so tumor cells can't repair themselves, and they stop growing. Giving atezolizumab in combination with talazoparib may help lower the chance of extensive-stage small cell lung cancer growing and spreading compared to atezolizumab alone.
Detailed Description

PRIMARY OBJECTIVE:

I. To compare progression free survival (PFS) among participants with Schlafen family member 11 (SLFN11) positive extensive stage small cell lung cancer (ES-SCLC) randomized to atezolizumab or atezolizumab plus talazoparib as maintenance therapy.

SECONDARY OBJECTIVES:

I. To compare overall survival (OS) between the arms. II. To compare objective response rate (ORR) among participants with measurable disease between the arms, including complete response (CR) and partial response (PR) (confirmed and unconfirmed) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

III. To evaluate the frequency and severity of adverse events within each treatment arm.

TRANSLATIONAL MEDICINE OBJECTIVE:

I. To bank specimens for future correlative studies.

OUTLINE: Patients are screened for SLFN11 biomarker during Step 1: Screening Registration by submitting tumor tissue to MDACC. Patients with SLFN11 biomarker are registered to Step 2: Randomization and are randomized to 1 or 2 arms.

ARM I: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive atezolizumab IV over 30-60 minutes on day 1 and talazoparib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 2 years and at the end of 3 years from randomization.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel 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: Talazoparib
    Given PO
    Other Names:
    • BMN 673
    • BMN-673
Study Arms  ICMJE
  • Active Comparator: Arm I (atezolizumab)
    Patients receive atezolizumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
    Intervention: Drug: Atezolizumab
  • Experimental: Arm II (atezolizumab, talazoparib)
    Patients receive atezolizumab IV over 30-60 minutes on day 1 and talazoparib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Talazoparib
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: April 3, 2020)
94
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 30, 2025
Estimated Primary Completion Date November 30, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • STEP 1: SCREENING REGISTRATION: Participants must have histologically or pathologically confirmed diagnosis of extensive stage small cell lung cancer (ES-SCLC) at the time of protocol entry. Participants with mixed histology are excluded
  • STEP 1: SCREENING REGISTRATION: Participants must have completed at least one cycle of frontline induction treatment with platinum plus etoposide plus atezolizumab prior to Step 1 Screening Registration. Cycle 1 of frontline induction treatment may or may not contain atezolizumab

    • NOTE: Participants may be screened while receiving consolidation thoracic radiation or during prophylactic cranial irradiation (PCI) at the time of Step 1 Screening Registration. Participants may or may not receive consolidation thoracic radiation and/or PCI per the discretion of their treating investigator
  • STEP 1: SCREENING REGISTRATION: Participants must not have received any immunotherapy for SCLC prior to starting the frontline induction treatment for ES-SCLC
  • STEP 1: SCREENING REGISTRATION: Participants must not have received any investigational agent for the treatment of ES-SCLC
  • STEP 1: SCREENING REGISTRATION: Participants must have adequate tumor tissue available from a core biopsy defined as:

    • At least two (3-5 microns) unstained slides, or;
    • One (3-5 microns) unstained slide plus one hematoxylin and eosin (H&E) stained slide
    • Participants must agree to have this tissue submitted to M.D. Anderson Cancer Center (MDACC) for SLFN11 immunohistochemistry (IHC) testing. Note: A histologic review will be performed at MDACC to confirm adequate cellularity for the testing. If inadequate cellularity, additional unstained slides from the same participant may be submitted if it doesn't exceed the window of starting maintenance therapy
  • STEP 1: SCREENING REGISTRATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
  • STEP 1: SCREENING REGISTRATION: As a part of the Oncology Participant Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
  • STEP 1: SCREENING REGISTRATION: Participants with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)
  • STEP 2: RANDOMIZATION: Site must have received notification from the SWOG Statistics and Data Management Center (SDMC) that the participant's tumor sample is SLFN11 positive
  • STEP 2: RANDOMIZATION: Participants must have their disease assessed either by computed tomography (CT) of chest/abdomen/pelvis (with contrast, unless contraindicated) within 28 days prior to Step 2 Registration or by positron emission tomography (PET)PET/CT of chest/abdomen/pelvis (with contrast, unless contraindicated)within 42 days prior to Step 2 Registration. Participants may have a complete response to induction therapy. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1).
  • STEP 2: RANDOMIZATION: Patients must have a CT or magnetic resonance imaging (MRI) scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to Step 2 randomization. Patient must not have leptomeningeal disease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment, and prior to Step 2 randomization, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to Step 2 randomization
  • STEP 2: RANDOMIZATION: Participants must not have had disease progression based on post induction imaging in the opinion of treating investigator
  • STEP 2: RANDOMIZATION: Participants must be registered to Step 2 Randomization prior to the start of maintenance atezolizumab
  • STEP 2: RANDOMIZATION: Participants must have received no fewer than 2 cycles and no more than 4 cycles of induction treatment with platinum/etoposide/atezolizumab
  • STEP 2: RANDOMIZATION: Participant must not have received radiation treatment (RT) or prophylactic cranial irradiation (PCI) within 14 days prior to Step 2 Randomization
  • STEP 2: RANDOMIZATION: Participants must not be taking strong P-glycoprotein (P-gp) inhibitors (e.g., dronedarone, quinidine, ranolazine), P-gp inducers (e.g., rifampin), or breast cancer resistance protein (BCRP) inhibitors (e.g., elacridar) within 7 days prior to randomization. Participants must not plan to receive the therapies listed above while on protocol treatment)
  • STEP 2: RANDOMIZATION: Participants must not have experienced the following during induction treatment:

    • Any grade 3 or worse immune-related adverse event (irAE) in the opinion of the treating investigator. Exception: asymptomatic nonbullous/nonexfoliative rash
    • Any unresolved grade 2 irAE
    • Any toxicity that led to permanent discontinuation of prior anti-PD-1/PD-L1 immunotherapy. Exception to the above: Toxicities of any grade that require replacement therapy and have stabilized on therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) are allowed
  • STEP 2: RANDOMIZATION: History and physical exam must be obtained within 28 days prior to Step 2 randomization
  • STEP 2: RANDOMIZATION: Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function and be considered class 2B or better on the New York Heart Association Functional Classification
  • STEP 2: RANDOMIZATION: Participants must have Zubrod performance status 0-2 documented within 28 days prior to Step 2 Randomization.
  • STEP 2: RANDOMIZATION: Leukocytes >= 3,000/mcL (within 28 days prior to Step 2 Randomization)
  • STEP 2: RANDOMIZATION: Absolute neutrophil count >= 1,500/mcL (within 28 days prior to Step 2 Randomization)
  • STEP 2: RANDOMIZATION: Platelets >= 100,000/mcL (within 28 days prior to Step 2 Randomization)
  • STEP 2: RANDOMIZATION: Total bilirubin =< institutional upper limit of normal (ULN) (within 28 days prior to Step 2 Randomization)
  • STEP 2: RANDOMIZATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional ULN (within 28 days prior to Step 2 Randomization)
  • STEP 2: RANDOMIZATION: Creatinine =< institutional ULN OR estimated creatinine clearance > 30 mL/min (within 28 days prior to Step 2 Randomization)
  • STEP 2: RANDOMIZATION: Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within in 6 months prior to Step 2 Randomization
  • STEP 2: RANDOMIZATION: Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment must have an undetectable HCV viral load within in 6 months prior to Step 2 Randomization
  • STEP 2: RANDOMIZATION: Participants with known human immunodeficiency virus (HIV) infection must be on effective anti-retroviral therapy and must have undetectable viral load at their most recent viral load test and within 6 months prior to Step 2 Randomization
  • STEP 2: RANDOMIZATION: Participants with known diabetes must not have uncontrolled diabetes. (Uncontrolled diabetes is defined as glycosylated hemoglobin [HgA1C] > 7%)
  • STEP 2: RANDOMIZATION: Participants must be able to swallow capsule whole
  • STEP 2: RANDOMIZATION: Participants must not have any known clinically significant liver disease, including cirrhosis, fatty liver, or inherited liver disease
  • STEP 2: RANDOMIZATION: Participants must not have end stage renal or other serious medical illness that may limit survival or the ability to participate in this study
  • STEP 2: RANDOMIZATION: Participants must not have a history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • STEP 2: RANDOMIZATION: Participants must not have known active tuberculosis (TB)
  • STEP 2: RANDOMIZATION: Participants must not have undergone prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • STEP 2: RANDOMIZATION: Participants must not have history of allergic reaction attributed to compounds of similar chemical or biological composition to atezolizumab and/or talazoparib
  • STEP 2: RANDOMIZATION: Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
  • STEP 2: RANDOMIZATION: Participants must not be on corticosteroids at doses greater than prednisone 10 mg daily or equivalent within 7 days prior to Step 2 Randomization
  • STEP 2: RANDOMIZATION: Participants must not receive any live attenuated vaccines within 28 days prior to Step 2 Randomization or at any time during the study and until 5 months after the last dose of protocol treatment
  • STEP 2: RANDOMIZATION: Participants must not have severe infections in the form of severe sepsis or septic shock including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia within 14 days prior to Step 2 Randomization
  • STEP 2: RANDOMIZATION: Participants must not be pregnant due to the potential teratogenic side effects of the protocol treatment. Women of reproductive potential and men must have agreed to use an effective contraception method for the duration of protocol treatment, and for 7 months after the last dose of protocol treatment. A woman is considered to be of "reproductive potential" if she has had a menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atezolizumab, breastfeeding must be discontinued prior to Step 2 Randomization
  • STEP 2: RANDOMIZATION: Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the SWOG Specimen Tracking System
  • STEP 2: RANDOMIZATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
  • STEP 2: RANDOMIZATION: As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
  • STEP 2: RANDOMIZATION: Participants with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)
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 NCT04334941
Other Study ID Numbers  ICMJE NCI-2020-02093
NCI-2020-02093 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S1929 ( Other Identifier: SWOG )
S1929 ( Other Identifier: CTEP )
U10CA180888 ( 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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
URL: https://grants.nih.gov/policy/sharing.htm
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Nagla Abdel Karim Southwest Oncology Group
PRS Account National Cancer Institute (NCI)
Verification Date March 2021

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