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Head and Neck Squamous Cell CarcinomaPhase 1NCT02318771

Radiation Therapy and MK-3475 for Patients With Recurrent/Metastatic Head and Neck Cancer, Renal Cell Cancer, Melanoma, and Lung Cancer

A Phase 1 study testing Radiation Therapy (RT) and MK-3475 in people with Head and Neck Squamous Cell Carcinoma and Metastatic Renal Cell Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.

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

This randomized clinical trial studies radiation therapy and MK-3475 in treating patients with head and neck cancer, kidney cancer, melanoma, or lung cancer that has returned, has spread to other parts of the body, or cannot be removed by surgery. Radiation therapy uses high-energy x-rays to kill tumor cells. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Radiation Therapy (RT) and MK-3475
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
1 siteUnited States
Study dates
5 Feb 2015to 25 Mar 2021
Phase
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

  • 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 provided tissue from an archival tissue sample ( < 6 months old) or newly obtained core biopsy of a tumor lesion before radiation therapy. A core biopsy will be required. It is mandatory to have post-radiation re-biopsy.
  • In addition to index lesion, there are ≥ 1 measurable lesion(s).
  • Have a performance status of ≤ 1 on the ECOG Performance Scale.
  • Demonstrate adequate organ function defined as the following:
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  • Absolute neutrophil count (ANC) ≥1,500 /mcL
  • Platelets ≥100,000 / mcL
  • Hemoglobin ≥9 g/dL or ≥5.6 mmol/L
  • Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.8 X upper limit of normal (ULN) OR
  • ≥50 mL/min for subject with creatinine levels > 1.8 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
  • Female subjects of childbearing potential should have a negative urine or serum pregnancy test. 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 2 weeks of the radiation therapy.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the radiation therapy.
  • Has had a prior monoclonal antibody within 4 weeks prior to radiation therapy 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 radiation therapy or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
  • Note: Prior radiation therapy does not necessary excludes patients. The index lesion may be acceptable for stereotactic radiosurgery (SRS) and this will be determined by radiation oncologist.
  • Note: If there are more than one symptomatic lesions, patients will be excluded if the lesions can't be encompassed within one radiation portal.
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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, squamous cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer that has undergone potentially curative therapy.
  • 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 radiation therapy 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 radiation treatment.
  • 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 Sjorgen's syndrome will not be excluded from the study.
  • Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  • 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, 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).
  • Has a known Human Immunodeficiency Virus infection (HIV 1/2 antibodies) or Acquired Immunodeficiency Syndrome((HIV/AIDS).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has received a live vaccine within 30 days prior to the radiation therapy.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sidney Kimmel Cancer Center at Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: An Exploratory Study to Investigate the Immunomodulatory Activity of Radiation Therapy (RT) in Combination With MK-3475 in Patients With Recurrent/Metastatic Head and Neck, Renal Cell Cancer, Melanoma and Lung Cancer

This randomized clinical trial studies radiation therapy and MK-3475 in treating patients with head and neck cancer, kidney cancer, melanoma, or lung cancer that has returned, has spread to other parts of the body, or cannot be removed by surgery. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as MK-3475, may block tumor growth by targeting certain cells and causing the immune system to attack the tumor. Studying the effects of MK-3475 with radiation therapy on the body may help doctors learn whether it may be an effective treatment for these solid tumors.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To investigate the immunomodulatory activity of radiation therapy (RT) or RT in combination with anti-programmed cell death 1 (PD)-1 antibody (MK-3475) in patients with recurrent/metastatic head and neck cancer, renal cell cancer, melanoma and lung cancer.

SECONDARY OBJECTIVES:

  1. To explore whether programmed cell death ligand 1 (PD-L1) expression is associated with treatment response to the combination of RT and PD-1 blockade in renal cell cancer (RCC), head and neck cancer (HNC), lung cancer and melanoma.

II. To explore whether circulating tumor cells can be used to determine PD-L1 expression.

III. To explore other immune-related biomarker changes after RT: soluble PD-L1, cytokines etc.

OUTLINE: Patients are randomized to 1 of 4 treatment arms.

ARM A1: Patients undergo radiation therapy on day 1 per standard of care and then undergo biopsy 3-10 days later. Beginning 0-7 days after biopsy, patients receive MK-3475 intravenously (IV) over 30 minutes on day 1. Courses of MK-3475 repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM A2: Patients undergo radiation therapy on days 1-5 and then undergo biopsy 3-10 days later. Beginning 0-7 days after biopsy, patients receive MK-3475 as in Arm A1.

ARM B1: Patients receive one dose of MK-3475 IV over 30 minutes on day 1 and then undergo 1 fraction of RT. Patients then receive MK-3475 IV over 30 minutes in the absence of disease progression or unacceptable toxicity.

ARM B2: Patients receive MK-3475 as in Arm B1 and undergo 5 fractions of RT.

After completion of study treatment, patients are followed up at approximately 30 days and then every 8 weeks.

Being tested
Radiation Therapy (RT), MK-3475
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Carcinoma, Renal Cell, Lung Neoplasms, Melanoma

What participants receive

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

  • Radiation Therapy (RT)Radiation

    Also called Radiation, Radiotherapy

    Undergo RT

  • MK-3475Drug

    Also called Pembrolizumab, Keytruda, lambrolizumab

    Given IV

Study groups in NCT02318771
Study groupRoleWhat they receive
A1: RT (1 fraction, 8 Gy) + MK-3475ExperimentalPatients undergo RT on day 1 per standard of care and then undergo biopsy 3-10 days later. Beginning 0-7 days after biopsy, patients receive MK-3475 IV over 30 minutes on day 1. Courses of MK-3475 repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Radiation: Radiation Therapy (RT); Drug: MK-3475
A2: RT (5 fractions, 4 Gy) + MK-3475ExperimentalPatients undergo RT on days 1-5 and then undergo biopsy 3-10 days later. Beginning 0-7 days after biopsy, patients receive MK-3475 as in Arm A1.
Receives: Radiation: Radiation Therapy (RT); Drug: MK-3475
B1: MK-3475 + RT (1 fraction, 8 Gy) + MK-3475ExperimentalPatients receive one dose of MK-3475 IV over 30 minutes on day 1 and then undergo 1 fraction of RT. Patients then receive MK-3475 IV over 30 minutes in the absence of disease progression or unacceptable toxicity.
Receives: Radiation: Radiation Therapy (RT); Drug: MK-3475
B2: MK-3475 + RT (5 fractions, 4 Gy) + MK-3475ExperimentalPatients receive MK-3475 as in Arm B1 and undergo 5 fractions of RT.
Receives: Radiation: Radiation Therapy (RT); Drug: MK-3475

What is being measured

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

  1. Change in PD-LI levels

    Within each cohort, the significance of change in PD-L1 will be assessed using an exact one-sided sign test. The null hypothesis is that the average change (post-pre) is less than or equal to 0 while the alternative hypothesis is that the average change is greater than 0. The proportion of patients with improvement will be estimated along with an exact 95% confidence interval. As an exploratory analysis, the proportion will also be estimated separately within each cohort for the head and neck cancer patients.

    Measured: Baseline to up to 10 days after last dose of RT

Secondary outcomes (4)

  1. Response rate

    Summarized by treatment cohort along with exact 95% binomial confidence intervals.

    Measured: Up to 4 years

  2. Rate of toxicities

    Summarized by treatment cohort along with exact 95% binomial confidence intervals.

    Measured: Up to 4 years

  3. Progression-free survival

    Estimated by treatment cohort using the Kaplan-Meier method.

    Measured: Up to 4 years

  4. Biomarker levels

    Repeated biomarker measurements will be modeled using mixed effects linear regression.

    Measured: Up to 10 days after last dose of RT

Timeline

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

  1. First posted17 Dec 2014 (estimated)
  2. Study start5 Feb 2015
  3. Primary completion5 Jun 2018
  4. Study completion25 Mar 2021

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02318771
Sponsor's protocol ID
14P.524
Other IDs
2014-085, JT 6980
Status last verified
May 2025
First submitted
11 Dec 2014
Last updated
15 May 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012 Mar 22;12(4):252-64. doi: 10.1038/nrc3239.

    PubMed 22437870

  • Weber JS. Practical management of immune-related adverse events from immune checkpoint protein antibodies for the oncologist. Am Soc Clin Oncol Educ Book. 2012:174-7. doi: 10.14694/EdBook_AM.2012.32.79.

    PubMed 24451730

  • Weber JS, Kahler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol. 2012 Jul 20;30(21):2691-7. doi: 10.1200/JCO.2012.41.6750. Epub 2012 May 21.

    PubMed 22614989

  • Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010 Aug 19;363(8):711-23. doi: 10.1056/NEJMoa1003466. Epub 2010 Jun 5.

    PubMed 20525992

  • Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2.

    PubMed 22658127

  • Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 Jun 28;366(26):2455-65. doi: 10.1056/NEJMoa1200694. Epub 2012 Jun 2.

    PubMed 22658128

  • Weber J, Thompson JA, Hamid O, Minor D, Amin A, Ron I, Ridolfi R, Assi H, Maraveyas A, Berman D, Siegel J, O'Day SJ. A randomized, double-blind, placebo-controlled, phase II study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage III or IV melanoma. Clin Cancer Res. 2009 Sep 1;15(17):5591-8. doi: 10.1158/1078-0432.CCR-09-1024. Epub 2009 Aug 11.

    PubMed 19671877

  • Lemech C, Arkenau HT. Novel treatments for metastatic cutaneous melanoma and the management of emergent toxicities. Clin Med Insights Oncol. 2012;6:53-66. doi: 10.4137/CMO.S5855. Epub 2012 Jan 5.

    PubMed 22253555

  • Phan GQ, Weber JS, Sondak VK. CTLA-4 blockade with monoclonal antibodies in patients with metastatic cancer: surgical issues. Ann Surg Oncol. 2008 Nov;15(11):3014-21. doi: 10.1245/s10434-008-0104-y. Epub 2008 Aug 21.

    PubMed 18716842

  • Bristol-Myers Squibb: YERVOY (ipilimumab): Serious and fatal immune- mediated adverse reactions-YERVOY Risk Evaluation and Mitigation Strategy (REMS). http://www.yervoy.com/hcp/rems.aspx

  • Bristol-Myers Squibb: YERVOY (ipilimumab) prescribing information revised March 2011. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125377s0000lbl.pdf

  • Janssen Biotech, Inc.: REMICADE (Infliximab) prescribing information revised September 2011. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.La bel_Appr ovalHistory#labelinfo

  • Alexander GS, Palmer JD, Tuluc M, Lin J, Dicker AP, Bar-Ad V, Harshyne LA, Louie J, Shaw CM, Hooper DC, Lu B. Immune biomarkers of treatment failure for a patient on a phase I clinical trial of pembrolizumab plus radiotherapy. J Hematol Oncol. 2016 Sep 23;9(1):96. doi: 10.1186/s13045-016-0328-4.

    PubMed 27663515

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Radiation Therapy (RT) and MK-3475 in people with Head and Neck Squamous Cell Carcinoma and Metastatic Renal Cell Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University 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 16 inclusion and 20 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 15 May 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?

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?

Change in PD-LI levels (time frame: Baseline to up to 10 days after last dose of RT). 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 NCT02318771, which also lists 13 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 15 May 2025.

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