Biomarker-Driven Therapy and Immunotherapy in Screening Participants with Recurrent or Stage IV Non-Small Cell Lung Cancer (The Expanded Lung-MAP Screening Trial)
- REGISTRATION ELIGIBILITY STEP 0
- Patients with adequate archival tissue should be registered directly to Step 1, without registering to Step 0. Patients who need the fresh biopsy must also submit whole blood for ctDNA testing. Patients who need a fresh biopsy to obtain adequate tumor tissue must also submit whole blood for ctDNA testing. These patients must be registered to Step 0 to obtain a patient ID number for the submission
- Patients registered to Step 0 are not registered to the LungMAP protocol. To participate in LungMAP, patients must be registered to Step 1 after evaluation of patient eligibility, including tumor tissue adequacy
- Patients registered at Step 0 must use the same Southwest Oncology Group (SWOG) patient identification (ID) for registration at Step 1
- REGISTRATION STEP 1
- Patients must have pathologically proven non-small cell lung cancer (all histologic types) confirmed by tumor biopsy and/or fine-needle aspiration. Disease must be Stage IV or recurrent. The primary diagnosis of non-small cell lung cancer should be established using the current World Health Organization (WHO)/International Association for the Study of Lung Cancer (IASLC)-classification of Thoracic Malignancies. All histologies, including mixed, are allowed
- Patients must either be eligible to be screened at progression on prior treatment or to be pre-screened prior to progression on current treatment; these criteria are: * Screening at progression on prior treatment: To be eligible for screening at progression, patients must have received at least one line of systemic therapy for any stage of disease (stages I-IV) and must have progressed during or following their most recent line of therapy ** For patients whose prior systemic therapy was for stage I-III disease only (i.e. patient has not received any treatment for stage IV or recurrent disease), disease progression on platinum-based chemotherapy must have occurred within one year from the last date that patient received that therapy. For patients treated with consolidation anti-PD-1 or anti-PD-L1 therapy for stage III disease, disease progression on consolidation anti-PD-1 or anti-PD-L1 therapy must have occurred within one year from the date or initiation of such therapy ** For patients whose prior therapy was for stage IV or recurrent disease, the patient must have received at least one line of a platinum-based chemotherapy regimen or anti-PD-1/PD-L1 therapy, alone or in combination (e.g. nivolumab or pembrolizumab) * Pre-Screening prior to progression on current treatment: ** To be eligible for pre-screening, current treatment must be for stage IV or recurrent disease and patient must have received at least one dose of the current regimen; patients must have previously received or currently be receiving a platinum-based chemotherapy regimen or anti-PD-1/PD-L1 therapy, alone or in combination (e.g. nivolumab or pembrolizumab); patients on first-line treatment are eligible upon receiving cycle 1, day 1 infusion; Note: Patients will not receive their sub-study assignment until they progress and the LungMAP Notice of Progression is submitted
- Patients must have adequate tumor tissue available, defined as >= 20% tumor cells and >= 0.2 mm^3 tumor volume * The local interpreting pathologist must review the specimen * The pathologist must sign the LungMAP Local Pathology Review Form confirming tissue adequacy prior to Step 1 registration
- Patients must agree to have this tissue submitted to Foundation Medicine for common broad platform Clinical Laboratory Improvement Amendments (CLIA) biomarker profiling and PD-L1. If archival tumor material is exhausted, then a new fresh tumor biopsy that is formalin-fixed and paraffin-embedded (FFPE) must be obtained. Patients who need the fresh biopsy must also submit whole peripheral blood for ctDNA testing. A tumor block or FFPE slides 4-5 microns thick must be submitted. Bone biopsies are not allowed. If FFPE slides are to be submitted, at least 12 unstained slides plus an Hematoxylin and eosin (H&E) stained slide, or 13 unstained slides must be submitted. However, it is strongly recommended that 20 FFPE slides be submitted * Note: Previous next-generation DNA sequencing (NGS) will be repeated if done outside this study for sub-study assignment
- Patients must agree to have any leftover tissue (tissue that remains after biomarker testing) retained for the use of correlative studies outlined in the sub-study treatment consents
- Patients with known EGFR sensitizing mutations, EGFR T790M mutation, ALK gene fusion, or ROS 1 gene rearrangement, or BRAF V600E mutation are not eligible unless they have progressed following all standard of care targeted therapy. EGFR/ALK/ROS/BRAF testing is not required prior to Step 1 registration, as it is included in the Foundation One testing for screening/pre-screening
- Patients must have Zubrod performance status 0-1 documented within 28 days prior to Step 1 registration
- Patients must also be offered participation in banking for future use of specimens
- Patients must be willing to provide prior smoking history as required on the LungMAP On-study Form
- 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
- Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
- SUB-STUDY ELIGIBILITY
- Patients must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 21 days prior to sub-study registration. Patients must have recovered (=< grade 1) from any side effects of prior therapy. Patients must not have received any radiation therapy within 14 days prior to sub-study registration
- Patients must have measurable disease documented by computed tomography (CT) or magnetic resonance imaging (MRI). The CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality. Measurable disease must be assessed within 28 days prior to sub-study registration. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non-measurable disease must be assessed within 42 days prior to sub-study registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form. Patients whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to sub-study registration. CT and MRI scans must be submitted for central review via TRIAD
- Patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to sub-study registration. 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 sub-study registration, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to sub-study registration
- Patients must not have any grade III/IV cardiac disease as defined by the New York Heart Association criteria (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, and myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia
- Patients must not have documented evidence of acute hepatitis or have an active or uncontrolled infection
- Patients with a known history of human immunodeficiency virus (HIV) seropositivity: * Must have undetectable viral load using standard HIV assays in clinical practice * Must have CD4 count >= 400/mcL * Must not require prophylaxis for any opportunistic infections (i.e., fungal, mycobacterium avium complex [MAC], or pneumocystis pneumonia [PCP] prophylaxis) * Must not be newly diagnosed within 12 months prior to sub-study registration.
- No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
South San Francisco
West Des Moines
Grosse Pointe Woods
Saint Louis Park
North Kansas City
Salt Lake City
White River Junction
Fond Du Lac
I. To test patient specimens to determine eligibility for participation in the biomarker-driven and non-matched sub-studies included within the Lung-MAP umbrella protocol.
I. To evaluate the screen success rate defined as the percentage of screened patients that register for a therapeutic sub-study.
II. To evaluate circulating tumor deoxyribonucleic acid (DNA) (ctDNA) and compare to the FMI Foundation tissue molecular profiling results in patients who submit a new biopsy for screening.
III. To establish a tissue/blood repository.
ANCILLARY STUDY S1400GEN OBJECTIVES:
I. To evaluate patient attitudes and preferences about return of somatic mutation findings suggestive of a germline mutation in the Lung-MAP Screening Study.
I. To evaluate Lung-MAP study physician attitudes and preferences about return of somatic mutation findings suggestive of a germline mutation in the Lung-MAP Screening Study.
II. To evaluate Lung-MAP patients’ and study physicians’ knowledge of cancer genomics.
III. To evaluate Lung-MAP patients’ and study physicians’ knowledge of the design of the Lung-MAP Screening Study.
IV. To explore whether physician and patient knowledge of cancer genomics and attitudes and preferences about return of genomic profiling findings are correlated.
Participants undergo collection of tumor tissue samples. Participants are then assigned to a biomarker-driven or non-match sub- study based on biomarker results of tumor tissue samples.
S1800A (NON-MATCH SUB-STUDY): Patients are randomized to 1 of 2 arms.
ARM A: Patients may receive docetaxel intravenously (IV) over 10-30 minutes on day 1, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, pemetrexed IV over 10 minutes on day 1 (non-squamous NSCLC patients only), or ramucirumab IV over 60 minutes combined with docetaxel IV over 10-30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive ramucirumab IV over 60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.
S1900A: Patients with genomic loss of heterozygosity (LOH) high and/or deleterious BRCA1/2 mutation receive rucaparib orally (PO) twice daily (BID) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
S1900C: Patients with STK11 somatic mutation or STK11 bi-allelic loss receive talazoparib PO daily and avelumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ANCILLARY STUDY S1400GEN (OPTIONAL) (CLOSED TO ACCRUAL AS OF 6/30/2019):
Patients and physicians of patients enrolled to Lung-MAP complete a telephone-based survey over 25-30 minutes (patients) or a web-based survey over 10-15 minutes (physicians) that focuses on knowledge, attitudes, and preferences about genetic findings.
After completion of study intervention, participants are followed up every 6 months for up to 3 years.
Trial Phase Phase II
Trial Type Screening
Vassiliki A. Papadimitrakopoulou
- Primary ID LUNGMAP
- Secondary IDs NCI-2018-01540
- Clinicaltrials.gov ID NCT03851445