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Solid TumorPhase 1NCT02608385

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

A Phase 1 study testing Stereotactic body radiotherapy (SBRT) and Pembrolizumab in people with Solid Tumor, run by University of Chicago at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor
What is being tested?
Stereotactic body radiotherapy (SBRT) and Pembrolizumab
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
117 participants
Where
1 siteUnited States
Study dates
Dec 2015to Nov 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

  • 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.
  • 0.25 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.
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  • 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
  • AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
  • Albumin ≥ 3.0 mg/dL
  • 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 should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  • Have an investigator determined life expectancy of at least 6 months.

Who cannot join

  • 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.
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  • 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.
  • 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 screening visit through 120 days after the last dose of trial treatment.
  • If known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA qualitative is detected) then patient is not eligible for cohorts including SBRT to liver lesions.
  • 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 are live attenuated vaccines and are not allowed.
  • Has had prior radiation therapy (defined as >10% of prior prescription dose) to the area planning to be treated with SBRT
  • Additional Criteria for Expansion Cohorts:
  • Partially Irradiated Large Volume Tumors Cohort
  • In addition to the criteria above, patients must have at least one lesion >65cc (~5cm diameter sphere) that is amenable to partial tumor irradiation.
  • Oligometastatic disease
  • In addition to the criteria above, patients must have disease limited to 4 total lesions or less, all of which are amenable to SBRT. Patients with oligometastatic disease at presentation or oligorecurrent disease are eligible. Patients who had more than 4 sites of disease previously, but had a complete response at other sites and limited progressive disease to 4 sites are eligible for participation. Partial tumor irradiation for lesions >65cc is permitted in this expansion cohort.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Chicago

    Chicago, Illinois, 60637

Other trials in United States

About this study

Official title: Phase I Study of PD1 Blockade by Pembrolizumab With Stereotactic Body Radiotherapy in Advanced Solid Tumors

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
Being tested
Stereotactic body radiotherapy (SBRT), Pembrolizumab

What participants receive

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

  • Stereotactic body radiotherapy (SBRT)Radiation

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

  • PembrolizumabDrug

    Also called Keytruda

    Pembrolizumab (200 mg) given every 3 weeks.

Study groups in NCT02608385
Study groupRoleWhat they receive
Dose Escalation CohortExperimentalPatients 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.
Receives: Radiation: Stereotactic body radiotherapy (SBRT); Drug: Pembrolizumab
Large Volume Tumors CohortExperimentalPatients 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.
Receives: Radiation: Stereotactic body radiotherapy (SBRT); Drug: Pembrolizumab
Oligometastatic CohortExperimentalPatients 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.
Receives: Radiation: Stereotactic body radiotherapy (SBRT); Drug: Pembrolizumab

What is being measured

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

  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

    Measured: 3 Months

Secondary outcomes (9)

  1. Rate of side effects

    To estimate rates of ≥ grade 3-4 adverse events, scored according to NCI CTCAE v. 4.0, by organ system

    Measured: 3 Months

  2. Rate of long term side effects

    Rates of long-term adverse events, scored according to NCI CTCAE v. 4.0,

    Measured: 24 Months

  3. Response rate

    Response rates will be tabulated with 90% confidence limits based on the binomial distribution.

    Measured: 24 Months

  4. Progression-free survival

    Progression-free survival will be estimated using the Kaplan-Meier method.

    Measured: 12 months

  5. Overall survival

    Measured: 24 months

  6. Local control of SBRT lesion

    Measured: 12 months

  7. Changes in tumor microenvironment caused by radiation treatment

    Measured: 1 week

  8. Effect of radiation and pembrolizumab on tumor control for lesions larger than 65cc

    Measured: 12 months

  9. Effect of combining radiation and pembrolizumab on local and distant tumor control

    Measured: 12 months

Timeline

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

  1. First posted18 Nov 2015 (estimated)
  2. Study startDec 2015
  3. Primary completion1 Apr 2022
  4. Study completionNov 2026 (estimated)

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
Sequential
Masking
None (open label)
Enrolment
117 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02608385
Sponsor's protocol ID
IRB15-1130
Status last verified
Jun 2025
First submitted
9 Nov 2015
Last updated
8 Jun 2025
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 37183819

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Stereotactic body radiotherapy (SBRT) and Pembrolizumab in people with Solid Tumor, run by University of Chicago 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 21 inclusion and 26 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: under way, not looking for participants, as of the sponsor's last update on 8 Jun 2025. 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?

This study is still under way. Results are not available in the source record yet.

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?

Recommended stereotactic body radiotherapy (SBRT) dose in combination with pembrolizumab. (time frame: 3 Months). 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 NCT02608385, which also lists 1 linked publication.

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 Jun 2025.

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