Study of PD1 Blockade by Pembrolizumab With Stereotactic Body Radiotherapy in Advanced Solid Tumors

NCT02608385 | Active Not Recruiting Phase 1

• 1 other identifier: IRB15-1130
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 1

Brief Summary

Phase I to determine safety of combining stereotactic body radiotherapy (SBRT) with pembrolizumab in patients with advanced solid tumors. The study will determine safe doses of radiation by organ site when used together with pembrolizumab. The study will also provide the opportunity to evaluate changes in the tumor caused by SBRT. The study will include 2 expansion cohorts:

• Partially Irradiated Large Volume Tumors Cohort: Patients with at least one lesion greater than 65cc amenable to SBRT followed by pembrolizumab.
• Oligometastatic Cohort: Patients with limited metastatic disease (4 or fewer lesions)

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Recommended stereotactic body radiotherapy (SBRT) dose in combination with pembrolizumab.

  To determine the recommended SBRT dose to various metastatic locations in patients with advanced solid tumors, and specifically in the lung in patients with NSCLC, in conjunction with pembrolizumab treatment. Each metastasis targeted with SBRT will be assigned to one of the seven "Metastasis Locations". Patients will receive 3 or 5 fractions of radiation as determined by the location of the metastases to be irradiated. Exact logistic regression 13 analyses will be conducted to model the probability of DLT as a function of site dose, number of metastatic sites, and cumulative body radiation. These analyses will be conducted separately for each site using all patients with lesions at that site. If these analyses suggest a high (\>=33%) probability of toxicity for a particular combination of predictors, dose recommendations may be modified

  3 Months

Secondary Outcomes (9)

• Rate of side effects

  3 Months

• Rate of long term side effects

  24 Months

• Response rate

  24 Months

• Progression-free survival

  12 months

• Overall survival

  24 months

Study Arms (3)

Dose Escalation Cohort

EXPERIMENTAL

Patients will be enrolled to receive specific doses of radiation (stereotactic body radiotherapy) given over 1 week followed by treatment with pembrolizumab. Pembrolizumab dosing will continue for up to 2 years or until patients have disease progression or unacceptable side effects. Enrollment will continue until best safe dose of SBRT is determined for each organ type.

Radiation: Stereotactic body radiotherapy (SBRT); Drug: Pembrolizumab

Large Volume Tumors Cohort

EXPERIMENTAL

Patients with large tumors will be enrolled and their tumors will be partially treated with (stereotactic body radiotherapy) given over 1 week followed by treatment with pembrolizumab. Pembrolizumab dosing will continue for up to 2 years or until patients have disease progression or unacceptable side effects.

Radiation: Stereotactic body radiotherapy (SBRT); Drug: Pembrolizumab

Oligometastatic Cohort

EXPERIMENTAL

Patients with few tumors (4 or less) will be enrolled and their tumors treated with (stereotactic body radiotherapy) given over 1 week followed by treatment with pembrolizumab. Pembrolizumab dosing will continue for up to 2 years or until patients have disease progression or unacceptable side effects.

Radiation: Stereotactic body radiotherapy (SBRT); Drug: Pembrolizumab

Interventions

Stereotactic body radiotherapy (SBRT) RADIATION

Patients will receive 3 or 5 doses of SBRT to the chosen metastases.

Dose Escalation Cohort; Large Volume Tumors Cohort; Oligometastatic Cohort

Pembrolizumab DRUG

Pembrolizumab (200 mg) given every 3 weeks.

Also known as: Keytruda

Dose Escalation Cohort; Large Volume Tumors Cohort; Oligometastatic Cohort

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide written informed consent/assent for the trial.
• Aged 18 years or older
• Have a histologically confirmed advanced solid tumor for which curative treatment is not available.
• Have undergone all appropriate standard of care treatment options (in the opinion of the treating investigator). Patients with NSCLC must have undergone EGFR and ALK testing and have received appropriate initial therapy.
• Have measurable disease based on RECIST 1.1 including at least two tumor lesions that meet criteria for multi-organ site ablative radiation therapy (MOSART) SBRT radiation.
• cc to 65 cc of viable tumor (i.e. primary disease or metastases) approximately 5cm in maximal dimension. Tumors larger than 65 cc can be partially treated. Patients accruing to the expansion cohort for partially irradiated large tumors must have at least one site of disease \>65cc.
• Metastases located in lung, liver, mediastinal/cervical node, Spinal/Paraspinal, Osseous, abdominal-pelvic (lymph node/adrenal gland)
• For biopsy patients: Be willing to undergo repeat biopsy of a tumor lesion before treatment and after radiation. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may be exempted from this requirement after consultation with the Principal Investigator.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Demonstrate adequate organ function
• Absolute neutrophil count (ANC) ≥ 1,500 /mcL
• Platelets ≥ 100,000 / mcL
• Hemoglobin ≥ 8 g/dL
• Serum creatinine OR Measured or calculateda creatinine clearance ≤ 1.5 X upper limit of normal (ULN) OR ≥ 50 mL/min for subject with creatinine levels \> 1.5 X institutional ULN
• Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN

You may not qualify if:

• 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 at a dose of \>10 mg Prednisone daily or equivalent at time of 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 side effects 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 a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of non-infectious pneumonitis that required steroids or active pneumonitis.
• Has evidence of interstitial lung disease.
• 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.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Related Publications (1)

• Korpics MC, Onderdonk BE, Dadey RE, Hara JH, Karapetyan L, Zha Y, Karrison TG, Olson AC, Fleming GF, Weichselbaum RR, Bao R, Chmura SJ, Luke JJ. Partial tumor irradiation plus pembrolizumab in treating large advanced solid tumor metastases. J Clin Invest. 2023 May 15;133(10):e162260. doi: 10.1172/JCI162260.

  PMID: 37183819 DERIVED

MeSH Terms

Interventions

Radiosurgery; pembrolizumab

Intervention Hierarchy (Ancestors)

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

Study Officials

• Steven Chmura, M.D.

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2015
• First Posted: November 18, 2015
• Study Start: December 1, 2015
• Primary Completion: April 1, 2022
• Study Completion (Estimated): November 1, 2026
• Last Updated: June 8, 2025

Record last verified: 2025-06

Locations

US (1)