A Pilot Study of MPDL3280A and HIGRT in Metastatic NSCLC

Completed · Early Phase 1

Conditions studied: Non-small Cell Lung Cancer

In brief

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.

Key facts

Study ID

NCT02463994

Run by

University of Michigan Rogel Cancer Center

People needed

12

Starts

2015-10-01

Expected to finish

2018-11-07

Last updated by the study team

2019-02-08

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• Any approved anticancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment; however, the following are allowed:
• Hormone-replacement therapy or oral contraceptives.
• Herbal therapy > 1 week prior to Cycle 1, Day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to Cycle 1, Day 1).
• Palliative radiotherapy for bone metastases < 2 weeks prior to Cycle 1, Day 1
• AEs from prior anticancer therapy that have not resolved to Grade ≤ 1 except for alopecia.
• Bisphosphonate therapy for symptomatic hypercalcemia.
• Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed.
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease.
• Patients with acute leukemias, accelerated/blast-phase chronic myelogenous leukemia, chronic lymphocytic leukemia (except Rai-stage I), Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma
• Known primary CNS (Central Nervous System) malignancy or symptomatic CNS metastases
• Patients with asymptomatic untreated CNS disease may be enrolled after consultation, provided all of the following criteria are met:
• Evaluable or measurable disease outside the CNS
• No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)
• No history of intracranial hemorrhage or spinal cord hemorrhage
• No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted
• No neurosurgical resection or brain biopsy within 28 days prior to Cycle 1, Day 1
• Patients with asymptomatic treated CNS metastases may be enrolled after consultation, provided all the criteria listed above are met as well as the following:
• Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
• No stereotactic radiation or whole-brain radiation within 28 days prior to Cycle 1, Day 1
• Screening CNS radiographic study ≥ 4 weeks from completion of radiotherapy and ≥ 2 weeks from discontinuation of corticosteroids
• Pregnancy, lactation, or breastfeeding
• Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• Inability to comply with study and follow-up procedures
• History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
• Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.

Where it is running

• The University of Michigan Comprehensive Cancer Center — Ann Arbor, Michigan, United States
• University of Washington, Seattle — Seattle, Washington, United States

Full record on ClinicalTrials.gov

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