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Non-small Cell Lung CancerEarly Phase 1NCT02463994

A Pilot Study of MPDL3280A and HIGRT in Metastatic NSCLC

A Early Phase 1 study testing MPDL3280A and Hypofractionated Radiotherapy in people with Non-small Cell Lung Cancer, run by University of Michigan Rogel Cancer Center at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer
What is being tested?
MPDL3280A and Hypofractionated Radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
2 sitesUnited States
Study dates
Oct 2015to 7 Nov 2018
Phase
Early 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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible.
  • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
  • Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
  • Rash must cover less than 10% of body surface area (BSA)
  • Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
  • No acute exacerbations of underlying condition within the last 12 months (not requiring PUVA [Psoralen Plus Ultraviolet A Radiation], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral steroids)
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan
  • History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
  • History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C infection
  • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [Antibody to Hepatitis B Core Antigen] antibody test) are eligible.
  • Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
  • Active tuberculosis
  • Severe infections within 4 weeks prior to Cycle 1, Day 1 including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1
  • Received oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1
  • Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
  • Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study
  • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study
  • Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study.
  • Malignancies other than disease under study within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., CLL Rai Stage 0, prostate cancer with Gleason score ≤ 6, and PSA ≤10 mg/mL, etc.)
  • Medication-Related Exclusion Criteria:
  • Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents
  • Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:
  • Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose
  • No history of severe immune-related adverse effects from anti-CTLA-4 (CTCAE Grade 3 and 4)
  • Treatment with systemic immunostimulatory agents (including but not limited to IFN, IL-2) within 6 weeks or five half-lives of the drug (whichever is shorter) prior to Cycle 1, Day 1
  • Treatment with investigational agent within 4 weeks prior to Cycle 1, Day 1 (or within five half-lives of the investigational product, whichever is longer)
  • Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents) within 2 weeks prior to Cycle 1, Day 1
  • Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled.
  • The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • Specific Exclusion Criteria:
  • Patients having no distinct measurable lesions outside of the field of radiation.
  • Previous radiotherapy to the lesion(s) of interest.
  • Concurrent treatment with any other anti-neoplastic drug or concurrent participation in another therapeutic clinical trial
  • Patients with EGFR/ALK/ROS-1+ lung adenocarcinoma.
  • Uncontrolled tumor-related pain.
  • Uncontrolled hypercalcemia

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • The University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • University of Washington, Seattle

    Seattle, Washington

Other trials in United States

About this study

Official title: A Pilot Study of MPDL3280A (PD-L1) Antibody Therapy and Hypofractionated Image-guided Radiotherapy (HIGRT) in Patients With Metastatic Non-Small Cell Lung Cancer

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.

Being tested
MPDL3280A, Hypofractionated Radiotherapy
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.

  • MPDL3280ADrug

    Patients will receive 1,200 mg I.V. Q 3 weeks of MPDL3280A until progression.

  • Hypofractionated RadiotherapyRadiation

    Hypofractionated Image-Guided Radiotherapy (HIGRT)

Study groups in NCT02463994
Study groupRoleWhat they receive
MPDL3280A + HIGRTExperimentalNot described
Receives: Drug: MPDL3280A; Radiation: Hypofractionated Radiotherapy

What is being measured

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

  1. The number of participants that respond to a combination of HIGRT and MPDL3280A (PD-L1)

    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.

    Measured: 5 years

Timeline

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

  1. First posted8 Jun 2015 (estimated)
  2. Study startOct 2015
  3. Primary completion7 Nov 2018
  4. Study completion7 Nov 2018

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
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02463994
Sponsor's protocol ID
UMCC 2015.005
Other IDs
HUM00100387
Status last verified
Feb 2019
First submitted
29 May 2015
Last updated
8 Feb 2019
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing MPDL3280A and Hypofractionated Radiotherapy in people with Non-small Cell Lung Cancer, run by University of Michigan Rogel Cancer Center at 2 sites 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 28 inclusion and 65 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: finished, as of the sponsor's last update on 8 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

The number of participants that respond to a combination of HIGRT and MPDL3280A (PD-L1) (time frame: 5 years). 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 NCT02463994.

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 8 Feb 2019.

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