NCI ID NCI-2020-02093
NCT ID NCT04334941
CTEP ID S1929
Primary Purpose TREATMENT
Anatomic Sites Lung
Minimum Age 18 Years
Maximum Age 999 Years
Gender BOTH
Lead Org SWOG
Principal Investigator Nagla Abdel Karim
NCI Site View on ClinicalTrials.gov

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

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.

Eligibility

Inclusion Criterea

  • 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 who have transformed to SCLC from lung non-small cell carcinoma (NSCLC) or have SCLC with mixed histology are not eligible
  • STEP 1: SCREENING REGISTRATION: Participants must have completed at least day 3 of cycle 1 dosing 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 or fine needle aspiration (FNA) defined as: * At least two (3-5 microns) (three slides preferred) unstained slides, or; * One (3-5 microns) (two slides preferred) unstained slide plus one 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 for measurable disease or by positron emission tomography (PET)PET/CT of chest/abdomen/pelvis (with contrast, unless contraindicated) within 42 days prior to Step 2 Registration for non-measurable disease. 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). Study participants will not be considered eligible if a non-diagnostic PET/CT of chest/abdomen/pelvis is used to assess measurable disease prior to Step 2 Registration
  • 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) participant 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 x 10^3/mL (within 28 days prior to Step 2 Randomization)
  • STEP 2: RANDOMIZATION: Absolute neutrophil count >= 1.5 x 10^3/mL (within 28 days prior to Step 2 Randomization)
  • STEP 2: RANDOMIZATION: Platelets >= 100 x 10^3/mL (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 must be able to swallow capsule whole
  • 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 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)

Exclusion Criterea


Participating Clinics

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital


808 North 39th Avenue
Yakima, WA 98902
Map

509-574-3535
Memorial-ClinicalTrials@yvmh.org

Comprehensive Cancer Centers of Nevada-Horizon Ridge


2460 West Horizon Ridge Parkway
Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

Ann M Wierman MD LTD


3150 Tenaya Way
Suite 200 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Kingman Regional Medical Center


3269 Stockton Hill Road
Kingman, AZ 86401
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada-Southeast Henderson


1505 Wigwam Parkway
Suite 130 Henderson, NV 89074
Map

702-384-0013
research@sncrf.org

Las Vegas Cancer Center-Henderson


2904 West Horizon Ridge Parkway
Suite 200 Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Henderson


52 North Pecos Road
Henderson, NV 89074
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Las Vegas


3006 South Maryland Parkway
Suite 100 Las Vegas, NV 89109
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-Tenaya


2851 North Tenaya Way
Suite 101 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Henderson


10001 South Eastern Avenue
Suite 108 Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

Carson Tahoe Regional Medical Center


1535 Medical Parkway
Pharmacy Suite C Carson City, NV 89703
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Northwest


7445 Peak Drive
Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Radiation Oncology Centers of Nevada Central


624 South Tonopah Drive
Las Vegas, NV 89106
Map

702-384-0013
research@sncrf.org

PCR Oncology


584 Camino Mercado
Arroyo Grande, CA 93420
Map

702-384-0013
research@sncrf.org

Radiation Oncology Associates


6630 B South McCarran
Suite 18 Reno, NV 89509
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada


9280 West Sunset Road
Suite 100 Las Vegas, NV 89148
Map

702-384-0013
research@sncrf.org

Alliance for Childhood Diseases/Cure 4 the Kids Foundation


One Breakthrough Way
Las Vegas, NV 89135
Map

702-384-0013
research@sncrf.org

Cancer and Blood Specialists-Henderson


2460 West Horizon Ridge Parkway
Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Central Valley


3730 South Eastern Avenue
Las Vegas, NV 89169
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway


3006 South Maryland Parkway
Suite 205 Las Vegas, NV 89109
Map

702-384-0013
research@sncrf.org

University Medical Center of Southern Nevada


1800 West Charleston Boulevard
Las Vegas, NV 89102
Map

702-384-0013
research@sncrf.org

Saint Mary's Regional Medical Center


235 West Sixth Street
Reno, NV 89503
Map

702-384-0013
research@sncrf.org

Renown Regional Medical Center


1155 Mill Street
Reno, NV 89502
Map

702-384-0013
research@sncrf.org

Sunrise Hospital and Medical Center


3186 South Maryland Parkway
Las Vegas, NV 89109
Map

702-384-0013
research@sncrf.org

Las Vegas Cancer Center-Medical Center


6450 Medical Center Street
Las Vegas, NV 89148-2405
Map

702-384-0013
research@sncrf.org

Radiation Oncology Centers of Nevada Southeast


3980 South Eastern Avenue
Las Vegas, NV 89119
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Fort Apache


6160 South Fort Apache Road
Las Vegas, NV 89148
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Vegas Tenaya


2851 North Tenaya Way
Suite 100 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at Fort Apache


6190 South Fort Apache Road
Las Vegas, NV 89148
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-San Martin


8285 West Arby Avenue
Suite 100 Las Vegas, NV 89113
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills


6850 North Durango Drive
Suite 120 Las Vegas, NV 89149
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada-Summerlin


655 North Town Center Drive
Las Vegas, NV 89144
Map

702-384-0013
research@sncrf.org

Summerlin Hospital Medical Center


657 Town Center Drive
Las Vegas, NV 89144
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Town Center


653 North Town Center Drive
Suite 402 Las Vegas, NV 89144
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at Seven Hills


3175 Saint Rose Parkway
Suite 200 Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

Hope Cancer Care of Nevada-Pahrump


2340 East Calvada Boulevard
Suite 7 Pahrump, NV 89048
Map

702-384-0013
research@sncrf.org

Desert West Surgery


1111 Shadow Lane
Las Vegas, NV 89102
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at Charleston


2300 West Charleston Boulevard
Las Vegas, NV 89102
Map

702-384-0013

Hope Cancer Care of Nevada


6827 West Tropicana Avenue
Suite 110 Las Vegas, NV 89103
Map

702-384-0013
research@sncrf.org

University Cancer Center


3131 La Canada Street
Suite 231 Las Vegas, NV 89169
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at MountainView


3150 North Tenaya Way
Suite 510 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Las Vegas Urology - Cathedral Rock


7200 Cathedral Rock Drive
Suites 180 and 210 Las Vegas, NV 89128
Map


research@sncrf.org

Las Vegas Urology - Pecos


9053 South Pecos Road
Suite 2900 Las Vegas, NV 89074
Map


research@sncrf.org

Las Vegas Prostate Cancer Center


7150 West Sunset Road
Suite 100 Las Vegas, NV 89113
Map


research@sncrf.org

Las Vegas Urology - Green Valley


1701 North Green Valley Parkway
Suite 10C Henderson, NV 89074
Map


research@sncrf.org

Las Vegas Urology - Pebble


8915 South Pecos Road
Suite 19A Henderson, NV 89074
Map


research@sncrf.org

Urology Specialists of Nevada - Northwest


3150 North Tenaya Way
Suite 165 Las Vegas, NV 89128
Map


research@sncrf.org

Urology Specialists of Nevada - Green Valley


58 North Pecos Road
Henderson, NV 89074
Map


research@sncrf.org

Urology Specialists of Nevada - Central


2010 Wellness Way
Suite 200 Las Vegas, NV 89106
Map


research@sncrf.org

Las Vegas Urology - Sunset


7150 West Sunset Road
Suite 201A and 202B Las Vegas, NV 89113
Map


research@sncrf.org

Urology Specialists of Nevada - Southwest


8410 West Warm Springs Road
Suite 10 Las Vegas, NV 89113
Map


research@sncrf.org

Valley Medical Center


400 South 43rd Street
Renton, WA 98055
Map

425-228-3440
research@valleymed.org