AzTrials
AzTrials

Non-Small Cell Lung CancerPhase 2PEMBRO-RTNCT02492568

Pembrolizumab After SBRT Versus Pembrolizumab Alone in Advanced NSCLC

A Phase 2 study testing pembrolizumab and Stereotactic Body Radiation Therapy in people with Non-Small Cell Lung Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.

Completed

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

Official record
Search all trials

Trial summary

To evaluate the increase in Overall Response Rate (ORR) in the pembrolizumab alone arm compared to the pembrolizumab after SBRT arm at 12 weeks 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?
pembrolizumab and Stereotactic Body Radiation Therapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
92 participants
Where
1 siteNetherlands
Study dates
Jul 2015to Jun 2018
Phase
Phase 2
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

  • Be willing and able to provide written informed consent/assent for the trial.
  • Be ≥ 18 years of age on day of signing informed consent.
  • Have measurable disease based on RECIST 1.1.
  • Must provide newly obtained tissue from a core or excisional biopsy of a tumor lesion and are willing to have a second biopsy performed form any non-irradiated lesion after the radiation and immune-modulating treatment.
  • Have a performance status of 0 or 1 on the ECOG Performance Scale.
  • Stage IV NSCLC; treated with at least 1 regimen of chemotherapy.
Show all 13Show fewer
  • Have at least 2 separate (metastatic) lesions of which one is amenable for irradiation with a size of < 5 cm.
  • Demonstrate adequate organ function:
  • Absolute neutrophil count (ANC) ≥1,500 /mcL; Platelets ≥100,000 / mcL; Hemoglobin ≥9 g/dL or ≥5.6 mmol/L; Serum creatinine ≤1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥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; International Normalized Ratio (INR) or Prothrombin Time (PT) and 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.
  • All screening labs should be performed within 10 days of treatment initiation.
  • 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 (Reference Section 5.7.2). 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.

Who cannot join

  • Is currently participating in or has participated in a study of an investigational agent or using 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 had a prior monoclonal antibody 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 or targeted small molecule therapy 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 a previously administered agent.
  • Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
  • Note: If subjects received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
Show all 19Show fewer
  • Have had previous radical radiation to any tumor site within 6 months prior to study Day 1.
  • Have known but untreated driver mutations of the EGFR gene or ALK translocation.
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. 8. 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 six 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 14 days prior to trial treatment.
  • 9. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjögren's syndrome will not be excluded from the study.
  • 10. Has evidence of symptomatic interstitial lung disease or an active, non-infectious pneumonitis.
  • 11. Has an active infection requiring systemic therapy. 12. 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.
  • 13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • 14. 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.
  • 15. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
  • 16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • 17. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • 18. Has received a live vaccine within 30 days prior to the first dose of trial treatment.
  • 19. Has had major surgery or major blood transfusions (>3 packed cells) in the past 3 months.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Antoni van Leeuwenhoek (NKI-AVL)

    Amsterdam, North Holland, 1066 CX

Other trials in Netherlands

About this study

Official title: Randomized Phase II, 2-arm Study of Pembrolizumab After High Dose Radiation (SBRT) Versus Pembrolizumab Alone in Patients With Advanced Non-small Cell Lung Cancer

To evaluate the increase in Overall Response Rate (ORR) in the pembrolizumab alone arm compared to the pembrolizumab after SBRT arm at 12 weeks

Read the detailed description

The investigators hypothesize that in a significant subset of patients with recurrent NSCLC immunotherapy after SBRT will be superior to treatment with immunotherapy alone and that SBRT, given to a single metastatic site of the tumor, will augment the immune response to the tumor. Objectives: Disease Control Rate (DCR), defined as the percentage of patients having a complete response, partial response or stable disease at 12 weeks, PFS, defined as time from randomization to disease progression or death, OS, defined as time from randomization to death (of any cause). Toxicity.

Keywords
recurrent, NSCLC, pembrolizumab, SBRT
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Recurrence

What participants receive

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

Study groups in NCT02492568
Study groupRoleWhat they receive
SBRT + PembrolizumabExperimentalStereotactic Body Radiation Therapy (SBRT) followed by pembrolizumab treatment within 7 days of completion. SBRT: 3 x 8 Gy, given 1-2 weeks prior to start of pembrolizumab. Dose of pembrolizumab is 200 mg, every 3 weeks. Patients can continue the pembrolizumab treatment for maximal 2 years.
Receives: Drug: pembrolizumab; Radiation: Stereotactic Body Radiation Therapy
Pembrolizumab aloneActive comparatorDose of pembrolizumab is 200 mg, every 3 weeks.Patients can continue the pembrolizumab treatment for maximal 2 years.
Receives: Drug: pembrolizumab

What is being measured

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

  1. Overall Response Rate

    Patients having a partial response or complete response are considered successes, while all other situations are considered failures.

    Measured: at 12 weeks

Secondary outcomes (4)

  1. The percentage of patients having a complete response, partial response or stable disease at 12 weeks

    Measured: at 12 weeks

  2. Time from randomization to disease progression or death

    Measured: Until progression, median 5 months

  3. Time from randomization to death (of any cause).

    Measured: every 12 weeks, median 5 months

  4. Toxicity; Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0

    Toxicity will be analyzed in patients who have received at least one administration of pembrolizumab.

    Measured: up to 30 days after end of treatment

Timeline

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

  1. First posted8 Jul 2015 (estimated)
  2. Study startJul 2015
  3. Primary completionJun 2018
  4. Study completionJun 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
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
92 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02492568
Sponsor's protocol ID
M14PRT
Other IDs
2014-003935-20, NL51468.031.14, 2014
Acronym
PEMBRO-RT
Status last verified
Aug 2020
First submitted
29 Jun 2015
Last updated
17 Aug 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • Theelen WSME, Chen D, Verma V, Hobbs BP, Peulen HMU, Aerts JGJV, Bahce I, Niemeijer ALN, Chang JY, de Groot PM, Nguyen QN, Comeaux NI, Simon GR, Skoulidis F, Lin SH, He K, Patel R, Heymach J, Baas P, Welsh JW. Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Respir Med. 2021 May;9(5):467-475. doi: 10.1016/S2213-2600(20)30391-X. Epub 2020 Oct 20.

    PubMed 33096027

  • Theelen WSME, Peulen HMU, Lalezari F, van der Noort V, de Vries JF, Aerts JGJV, Dumoulin DW, Bahce I, Niemeijer AN, de Langen AJ, Monkhorst K, Baas P. Effect of Pembrolizumab After Stereotactic Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients With Advanced Non-Small Cell Lung Cancer: Results of the PEMBRO-RT Phase 2 Randomized Clinical Trial. JAMA Oncol. 2019 Sep 1;5(9):1276-1282. doi: 10.1001/jamaoncol.2019.1478.

    PubMed 31294749

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing pembrolizumab and Stereotactic Body Radiation Therapy in people with Non-Small Cell Lung Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.

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 13 inclusion and 19 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 17 Aug 2020. 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 Netherlands. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Overall Response Rate (time frame: at 12 weeks). 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 NCT02492568, which also lists 2 linked publications.

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 17 Aug 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in