Pembrolizumab with or without Stereotactic Radiosurgery in Treating Patients with Stage I-IIIa Non-small Cell Lung Cancer

Status: Active

Description

This phase II trial studies how well pembrolizumab with or without stereotactic radiosurgery work in treating patients with stage I-IIIa non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. It is not yet known whether giving pembrolizumab with or without stereotactic radiosurgery may work better in treating patients with stage I-IIIa non-small cell lung cancer.

Eligibility Criteria

Inclusion Criteria

  • Histologically or cytologically confirmed non-small cell lung cancer, performed on a biopsy that occurred within the last 120 days
  • Positron emission tomography (PET)-computed tomography (CT) within the last 75 days showing radiographic stage I to IIIa lung cancer (mediastinal staging biopsy is allowed but not required)
  • Documentation that the patient is a candidate for surgical resection of their lung cancer by an American Board of Thoracic Surgery-certified surgeon
  • Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
  • Adequate tissue specimens for correlative biomarker analysis; the patient should be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion; newly-obtained is defined as a specimen obtained up to120 days prior to initiation of treatment on day 1; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the principal investigator
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  • Resolution of all acute toxic effects of prior chemotherapy, radiotherapy or surgical procedures to National Cancer Institute (NCI) CTCAE version 4.0 grade 1
  • Be willing and able to provide written informed consent/assent for the trial
  • Performed within 10 days of treatment initiation: Absolute neutrophil count (ANC) >= 1,500 /mcL
  • Performed within 10 days of treatment initiation: Platelets >= 100,000/mcL
  • Performed within 10 days of treatment initiation: Hemoglobin >= 9 g/dL or >= 5.6 mmol/L * Patients cannot have received transfusion or erythropoietin (EPO) within 7 days of the hemoglobin (Hgb) lab test
  • Performed within 10 days of treatment initiation: Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN * Creatinine clearance should be calculated per institutional standard
  • Performed within 10 days of treatment initiation: Serum total bilirubin =< 1.5 X ULN
  • Performed within 10 days of treatment initiation: aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN
  • Performed within 10 days of treatment initiation: International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial prothrombin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Performed within 10 days of treatment initiation: Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Female subjects of childbearing potential must be willing to use an adequate method of contraception; contraception, for the course of the study through 120 days after the last dose of study medication * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
  • Male subjects of childbearing potential must agree to use an adequate method of contraception; contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject

Exclusion Criteria

  • Is ineligible for an operation based on medical or oncologic contraindications to surgery
  • Has known history of, or any evidence of active, non-infectious pneumonitis that required steroids, or current pneumonitis
  • Has evidence of interstitial lung disease
  • Has an active second malignancy, i.e. patient known to have potentially fatal cancer present for which he/she may be (but not necessarily) currently receiving treatment; patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enroll in the trial if curative therapy has been completed, such as basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
  • Has a known history of active TB (Bacillus tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent * Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study * Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Has an active infection requiring systemic therapy
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Has received a live vaccine within 30 days of planned start of study therapy * Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed

Locations & Contacts

California

San Francisco
UCSF Medical Center-Mount Zion
Status: Active
Contact: Sue Sun Yom
Email: Sue.Yom@ucsf.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the change in the number of infiltrating CD3+ T cells/um^2 in the lung cancer tissue between the paired biopsy and thoracotomy specimens, as quantified by immunohistochemistry (IHC) and image analysis.

SECONDARY OBJECTIVES:

I. To assess the safety of preoperative pembrolizumab +/- stereotactic radiosurgery (stereotactic radiotherapy [SRT]) when combined with surgery.

II. To record the toxicity of preoperative pembrolizumab +/- SRT when combined with surgery, according to Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4, including immune-related adverse events (AEs).

III. To determine the 1-year overall survival rate resulting from preoperative pembrolizumab +/- SRT when combined with surgery.

IV. To determine the 1-year relapse free survival rate resulting from preoperative pembrolizumab +/- SRT when combined with surgery.

V. To determine the 1-year rate of distant metastases resulting from preoperative pembrolizumab +/- SRT when combined with surgery.

VI. To assess quality of life associated with preoperative pembrolizumab +/- SRT when combined with surgery.

VII. To determine the rate of unresectability that results from a program of preoperative pembrolizumab +/- SRT to be followed by a planned surgery.

TERTIARY OBJECTIVES:

I. To determine the difference in the number of infiltrating T cell subsets (cytotoxic CD8+, helper CD4+ FOXP3-, and regulatory CD4+ FOXP3+ T cells) between the biopsy and the surgery specimens, as quantified by IHC and image analysis.

II. To determine the change in the intratumoral T-cell repertoire by T cell receptor (TCR) sequencing and single-cell T-cell profiling.

III. To quantify treatment-induced changes in the circulating T cell immune response using TCR sequencing and enzyme-linked immunospot (ELISPOT) assays.

OUTLINE: Patients are randomized into 1 of 2 arms.

ARM I: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unaccepted toxicity.

ARM II: Patients receive pembrolizumab as in Arm I. Patients also undergo SRT within 7 days of second pembrolizumab course.

After completion of study treatment, patients are followed up at 30, 90, 180, and 360 days.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
UCSF Medical Center-Mount Zion

Principal Investigator
Sue Sun Yom

Trial IDs

Primary ID 166520
Secondary IDs NCI-2017-01727, 17-21952
Clinicaltrials.gov ID NCT03217071