Non-small Cell Lung Cancer
Conditions
Brief summary
The purpose of this study is to find out whether a brief course of radiation therapy given to one area affected by the cancer will improve the chances of responding to immuno-therapy in the form of a medicine called MPDL3280A, an antibody against PD-L1. PD-L1 is expressed on lung cancers and is known to block the effects of the body's immune system in attacking the cancer. Blocking this PD-L1 has been shown to improve the body's immune cells to attack and kill the cancer cells in non-small cell lung cancer. The goal of this study is to see if prior treatment with radiation will allow improved recognition of the cancer by the body's immune cells in the presence of MPDL3280A.
Interventions
DRUGMPDL3280A
Patients will receive 1,200 mg I.V. Q 3 weeks of MPDL3280A until progression.
RADIATIONHypofractionated Radiotherapy
Hypofractionated Image-Guided Radiotherapy (HIGRT)
Sponsors
University of Washington
University of Michigan Rogel Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed Informed Consent Form (ICF) * Ability and willingness to comply with the requirements of the study protocol * Age ≥18 years old * ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0 or 1 (scores run from 0 to 5 where 0 denotes perfect health and 5 death). * Patients with ECOG PS of 2, secondary to the underlying disease, may be enrolled. * Patients with Stage IIIB (not eligible for definitive chemo-radiotherapy), Stage IV, or recurrent non-small cell lung cancer (NSCLC); patients with Stage IV NSCLC should have previously received platinum based doublet chemotherapy. Patients with a new diagnosis of Stage IV NSCLC are eligible if they have an initial requirement for palliative XRT for symptomatic lesion (example: painful bone lesion or obstructive airway). * Patients must be candidates for palliative radiation. * Measurable disease per mRECIST v1.1 Patients must have at least 1 distinct site of measurable disease, ≥ 1 cm in its largest diameter, in addition to the site that is being irradiated. * Patients may have additional measurable and/or non-measurable but radiographically visible metastatic lesions (e.g. bone metastases). * Patients with treated brain metastasis as long as neurologically stable and not on steroids for at least 12 weeks (see
Exclusion criteria
below for details). * Patients must be candidates for PD-L1 Ab as determined by the treating physician * At least 3 weeks must have elapsed from any prior chemotherapy, and the patient must have recovered from side effects to ≤ grade 1 toxicities. * Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1): * ANC (Absolute Neutrophil Count) ≥ 1500 cells/µL * WBC (White Blood Cell) counts \> 2500/µL * Lymphocyte count ≥ 500/µL * Platelet count ≥ 100,000/µL; for patients with hematologic malignancies, platelet count ≥ 75,000/µL * Hemoglobin ≥ 9.0 g/dL * Total bilirubin ≤ 1.5 x ULN with the following exception: * Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled. * AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase) ≤ 3.0 x ULN with the following exception: Patients with liver involvement: AST and/or ALT ≤ 5 x ULN * Alkaline phosphatase ≤ 2.5 x ULN with the following exception: Patients with documented liver involvement or bone metastases: alkaline phosphatase ≤ 5 x ULN * Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation: (140 - age) x (weight in kg) x (0.85 if female) 72 x (serum creatinine in mg/dL) * INR (International Normalized Ratio) and aPTT ≤1.5 x ULN * This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such as low molecular weight heparin or warfarin) should be on a stable dose. * For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective form(s) of contraception (i.e., one that results in a low failure rate \[\<1% per year\] when used consistently and correctly) and to continue its use for 6 months after the last dose of MPDL3280A * Representative tumor specimens in paraffin blocks (preferred) or at least 15 unstained slides, with an associated pathology report, requested at any time prior to study entry. Only tissue from core needle, punch, or excisional biopsy sample collection will be accepted. Fine-needle aspiration, brushing, and lavage samples are not acceptable. For all biopsy types, submitted blocks should have sufficient tissue to generate at least 15 sections, and tissue for which the pathology report specifies that the overall tumor content is low (e.g., sparse or scant) is not acceptable. Tissue from separate time points (such as time of initial diagnosis and time of metastatic diagnosis) or from the multiple metastatic tumors may also be collected for a given patient, on the basis of availability. * If archival tissue is either insufficient or unavailable, the patient may still be eligible if the patient can provide at least five unstained, serial slides or is willing to consent to and undergo a pre-treatment core or excisional biopsy sample collection of the tumor. Fine-needle aspiration, brushing, and lavage samples are not acceptable.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The number of participants that respond to a combination of HIGRT and MPDL3280A (PD-L1) | 5 years | The primary outcome is overall response rate (ORR) to combination of HIGRT and MPDL3280A. The number of participants that respond to treatment will be determined. Response will be assessed by Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1, using primarily CT scans, immune response criteria and/or clinical benefit as assessed by the investigator. |
Countries
United States
Outcome results
None listed