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Recurrent Non-Small Cell Lung CarcinomaPhase 1NCT02400814

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

A Phase 1 study testing Anti-PD-L1 Monoclonal Antibody MPDL3280A and Stereotactic Body Radiation Therapy in people with Recurrent Non-Small Cell Lung Carcinoma and Stage IV Non-Small Cell Lung Cancer, run by Megan Daly, MD at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 19 years and older
What is being tested?
Anti-PD-L1 Monoclonal Antibody MPDL3280A and Stereotactic Body Radiation Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteUnited States
Study dates
3 Dec 2015to 29 Sep 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Serum bilirubin =< 1.0 x ULN
  • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN (for patients on anticoagulation they must be receiving a stable dose for at least 1 week prior to randomization)
  • Creatinine clearance >= 30 mL/min by Cockcroft-Gault formula
  • No history of severe hypersensitivity reactions to other monoclonal antibodies (mAbs)
  • No other active malignancy
  • No active autoimmune disease or a history of known or suspected autoimmune disease
  • No chemotherapy or radiotherapy within the past 28 days and patients must have recovered any acute toxicity associated with their most recent previous treatment
  • Any number of prior treatments is allowed; must have failed at least 1 treatment regimen for metastatic disease
  • 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

Who cannot join

  • 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
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  • 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
  • Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible
  • Patients with a prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • A history of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Positive test for human immunodeficiency virus (HIV)
  • Patients with active hepatitis B (defined as a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C
  • Patients with past hepatitis B virus infection or resolved hepatitis B virus (HBV) infection (defined as a negative HBSAg test and a positive antibody to hepatitis B core antigen antibody test) are eligible
  • Patients with a hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
  • Active tuberculosis
  • Administration of a live, attenuated vaccine within 4 weeks prior to enrollment or anticipation that such a live attenuated vaccine will be required during the study
  • Prior treatment with a cluster of differentiation (CD)137 agonists, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), anti-programmed cell death 1 (PD-1), or anti-PD-L1 therapeutic antibody or pathway targeting agents
  • Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrollment
  • Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, anti-tumor necrosis factor agents) within 2 weeks prior to enrollment or anticipated requirement for systemic immunosuppressive medications during the trial
  • Patients who have received acute, low dose, systemic immunosuppressant medication (e.g., a one-time dose of dexamethasone for nausea) may be enrolled after a discussion and approval by the principal investigator
  • The use of inhaled corticosteroids and mineralocorticoids (eg, fludrocortisone) is allowed

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California Davis

    Sacramento, California, 95817

Other trials in United States

About this study

Official title: Pilot Study of MPDL3280A Plus Stereotactic Ablative Radiotherapy (SAR) in Stage IV Non-small Cell Lung Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine which administration schedule of MPDL3280A (anti-PD-L1 monoclonal antibody MPDL3280A) and stereotactic ablative radiotherapy (SAR) will be most promising to move forward to a phase II trial based on safety and objective response rate.

SECONDARY OBJECTIVES:

  1. To define the safety and toxicity profile of MPDL3280A plus SAR using Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v4).

II. Radiographic response rates by immure-related Response Evaluation Criteria in Solid Tumors (irRECIST).

III. Progression free survival using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and irRECIST.

TERTIARY OBJECTIVES:

  1. Conduct correlative immunologic endpoints.

OUTLINE: Patients are assigned to 1 of 3 arms.

ARM I (CONCURRENT COHORT): Patients receive anti-PD-L1 monoclonal antibody MPDL3280A intravenously (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.

ARM II (INDUCTION COHORT): 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.

ARM III (SEQUENTIAL COHORT): 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.

After completion of study treatment, patients are followed up for 30 days.

Being tested
Anti-PD-L1 Monoclonal Antibody MPDL3280A, Stereotactic Body Radiation Therapy
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02400814
Study groupRoleWhat they receive
Arm I (concurrent cohort)ExperimentalPatients 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.
Receives: Drug: Anti-PD-L1 Monoclonal Antibody MPDL3280A; Radiation: Stereotactic Body Radiation Therapy
Arm II (induction cohort)ExperimentalPatients 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.
Receives: Drug: Anti-PD-L1 Monoclonal Antibody MPDL3280A; Radiation: Stereotactic Body Radiation Therapy
Arm III (sequential cohort)ExperimentalPatients 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.
Receives: Drug: Anti-PD-L1 Monoclonal Antibody MPDL3280A; Radiation: Stereotactic Body Radiation Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 30 days after completion of study treatment

  2. Response rate using irRECIST

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

    Measured: Up to 30 days after completion of study treatment

  3. 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Mar 2015 (estimated)
  2. Study start3 Dec 2015
  3. Primary completion29 Sep 2021
  4. Study completion29 Sep 2021

Why it stopped: Enrollment halted due to slow accrual.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02400814
Sponsor's protocol ID
685389
Other IDs
UCDCC#251, ML29551, UCDCC#251, P30CA093373, NCI-2014-02629
Status last verified
Aug 2022
First submitted
22 Jan 2015
Last updated
4 Aug 2022
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Anti-PD-L1 Monoclonal Antibody MPDL3280A and Stereotactic Body Radiation Therapy in people with Recurrent Non-Small Cell Lung Carcinoma and Stage IV Non-Small Cell Lung Cancer, run by Megan Daly, MD at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Enrollment halted due to slow accrual.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (time frame: Up to 30 days after completion of study treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02400814.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2022.

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