MPDL3280A and Stereotactic Ablative Radiotherapy in Patients With Non-small Cell Lung Cancer

NCT02400814 | Terminated Phase 1 DMC

• 5 other identifiers: 685389UCDCC#251ML29551P30CA093373NCI-2014-02629
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot phase I trial compares administration schedules of anti-programmed cell death-1 ligand 1 (PD-L1) monoclonal antibody MPDL3280A and stereotactic ablative radiotherapy in treating patients with stage IV non-small cell lung cancer. Monoclonal antibodies, such as anti-PD-L1 monoclonal antibody MPDL3280A, may block tumor growth in different ways by targeting certain cells. Stereotactic ablative radiotherapy, also known as stereotactic body radiation therapy, is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may kill more tumor cells and cause less damage to normal tissue. Giving anti-PD-L1 monoclonal antibody MPDL3280A with stereotactic ablative radiotherapy may be a better treatment for non-small cell lung cancer. However, it is not yet known what the best administration schedule is for these treatments.

Conditions

Recurrent Non-Small Cell Lung Carcinoma; Stage IV Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events

  Adverse events observed will be summarized in terms of type (organ affected or laboratory determination), severity (by National Cancer Institute CTCAE v4 and nadir or maximum values for the laboratory measures), time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.

  Up to 30 days after completion of study treatment

• Response rate using irRECIST

  All responses will be reported. Response rate among patients with measurable disease will be summarized by exact binomial confidence intervals.

  Up to 30 days after completion of study treatment

• Progression free survival using RECIST 1.1 and irRECIST

  Progression free survival will be summarized with Kaplan-Meier plots to describe the outcome of patients treated on this protocol. The median progression free survival time will be estimated using standard life table methods.

  From start of treatment to time of progression or death, whichever occurs first, assessed up to 30 days after completion of study treatment

Other Outcomes (1)

• Changes in biomarkers

  Baseline to up to 30 days after completion of study treatment

Study Arms (3)

Arm I (concurrent cohort)

EXPERIMENTAL

Patients receive anti-PD-L1 monoclonal antibody MPDL3280A IV over 30-60 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of course 1, patients also undergo SAR 2-3 times per week (with a minimum of 40 hours and a maximum of 96 hours between fractions) over 1.5-2 weeks for a total of 5 fractions.

Drug: Anti-PD-L1 Monoclonal Antibody MPDL3280A; Radiation: Stereotactic Body Radiation Therapy

Arm II (induction cohort)

EXPERIMENTAL

Patients receive anti-PD-L1 monoclonal antibody MPDL3280A IV over 30-60 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of course 3, patients also undergo SAR 2-3 times per week (with a minimum of 40 hours and a maximum of 96 hours between fractions) over 1.5-2 weeks for a total of 5 fractions.

Drug: Anti-PD-L1 Monoclonal Antibody MPDL3280A; Radiation: Stereotactic Body Radiation Therapy

Arm III (sequential cohort)

EXPERIMENTAL

Patients undergo SAR 2-3 times per week (with a minimum of 40 hours and a maximum of 96 hours between fractions) over 1.5-2 weeks for a total of 5 fractions beginning on day 1 of course 1. After completion of SAR (beginning on day 1 of course 2), patients receive anti-PD-L1 monoclonal antibody MPDL3280A IV over 30-60 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Anti-PD-L1 Monoclonal Antibody MPDL3280A; Radiation: Stereotactic Body Radiation Therapy

Interventions

Anti-PD-L1 Monoclonal Antibody MPDL3280A DRUG

Given IV

Also known as: MPDL3280A, RG7446

Arm I (concurrent cohort); Arm II (induction cohort); Arm III (sequential cohort)

Stereotactic Body Radiation Therapy RADIATION

Undergo SAR

Also known as: SBRT

Arm I (concurrent cohort); Arm II (induction cohort); Arm III (sequential cohort)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Ability to comply with the protocol
• Adults with histologically proven stage IV non-small cell lung cancer
• At least two sites of measurable disease as defined by RECIST 1.1; one of which must be amenable to treatment with SAR and accessible for optional pre- and post- treatment biopsy; if a pulmonary nodule is being considered for SAR it must range in size from 1-3 cm
• Have provided written consent for mandatory pre- and post-treatment biopsy (expansion cohort only)
• Patients with treated supratentorial metastases are allowed if stable, the patient is off steroids and no evidence of intracranial hemorrhage
• Archival tumor sample available; a minimum of 10 unstained slides; no fine needle aspiration (FNAs) allowed or tumor tissue from bone
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Life expectancy \>= 3 months
• Absolute neutrophil count (ANC) \>= 1500 cells/ul
• White blood cell (WBC) count \> 2500/uL
• Lymphocyte count \>= 500/uL
• Platelet count \>= 100,000/uL
• Hemoglobin \>= 9 g/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 x upper limit of normal (ULN) with alkaline phosphatase =\< 2.5 x ULN OR AST and ALT =\< 1.5 x ULN, with alkaline phosphatase \> 2.5 x ULN

You may not qualify if:

• Patients whose tumors contain activating epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangement should be excluded from this study, unless disease has progressed on all available, approved therapies targeting the EGFR mutation or ALK rearrangement
• Active or untreated central nervous system (CNS) metastases
• Leptomeningeal disease
• Uncontrolled pleural or pericardial effusion or ascites that would require recurrent drainage
• Uncontrolled tumor related pain
• Uncontrolled hypercalcemia
• Pregnant and lactating women
• Uncontrolled concomitant disease
• Significant cardiovascular disease (New York Heart Association class II or greater); myocardial infarction within 3 months prior to enrollment, unstable arrhythmias, unstable angina or a patient with a known left ventricular ejection fraction (LVEF) \< 40%
• Severe infection within 4 weeks prior to enrollment
• Oral or IV antibiotics within 2 weeks prior to enrollment
• History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity or allergy to Chinese hamster ovary cell products or any component of the MDPL3280A formulation
• History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
• Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible

Sponsors & Collaborators

• Megan Daly, MD: lead
• National Cancer Institute (NCI): collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

University of California Davis

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

atezolizumab; Radiosurgery

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Karen Kelly

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Clinical Radiation Oncology

Study Record Dates

• First Submitted: January 22, 2015
• First Posted: March 27, 2015
• Study Start: December 3, 2015
• Primary Completion: September 29, 2021
• Study Completion: September 29, 2021
• Last Updated: August 4, 2022

Record last verified: 2022-08

Locations

US (1)