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

NCT02318771 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: 14P.5242014-085JT 6980
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Head and Neck Squamous Cell Carcinoma; Metastatic Renal Cell Cancer; Recurrent Head and Neck Carcinoma; Recurrent Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IV Lung Cancer; Stage IV Skin Melanoma

Outcome Measures

Primary Outcomes (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.

  Baseline to up to 10 days after last dose of RT

Secondary Outcomes (4)

• Response rate

  Up to 4 years

• Rate of toxicities

  Up to 4 years

• Progression-free survival

  Up to 4 years

• Biomarker levels

  Up to 10 days after last dose of RT

Study Arms (4)

A1: RT (1 fraction, 8 Gy) + MK-3475

EXPERIMENTAL

Patients 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.

Radiation: Radiation Therapy (RT); Drug: MK-3475

A2: RT (5 fractions, 4 Gy) + MK-3475

EXPERIMENTAL

Patients 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.

Radiation: Radiation Therapy (RT); Drug: MK-3475

B1: MK-3475 + RT (1 fraction, 8 Gy) + MK-3475

EXPERIMENTAL

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.

Radiation: Radiation Therapy (RT); Drug: MK-3475

B2: MK-3475 + RT (5 fractions, 4 Gy) + MK-3475

EXPERIMENTAL

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

Radiation: Radiation Therapy (RT); Drug: MK-3475

Interventions

Radiation Therapy (RT) RADIATION

Undergo RT

Also known as: Radiation, Radiotherapy

A1: RT (1 fraction, 8 Gy) + MK-3475; A2: RT (5 fractions, 4 Gy) + MK-3475; B1: MK-3475 + RT (1 fraction, 8 Gy) + MK-3475; B2: MK-3475 + RT (5 fractions, 4 Gy) + MK-3475

MK-3475 DRUG

Given IV

Also known as: Pembrolizumab, Keytruda, lambrolizumab

A1: RT (1 fraction, 8 Gy) + MK-3475; A2: RT (5 fractions, 4 Gy) + MK-3475; B1: MK-3475 + RT (1 fraction, 8 Gy) + MK-3475; B2: MK-3475 + RT (5 fractions, 4 Gy) + MK-3475

Eligibility Criteria

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

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (13)

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  PMID: 22658127 BACKGROUND

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• 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

  BACKGROUND

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

  BACKGROUND

• 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

  BACKGROUND

• 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.

  PMID: 27663515 DERIVED

Related Links

• Sidney Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Jefferson University Hospitals

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Renal Cell; Lung Neoplasms; Melanoma

Interventions

Radiotherapy; Radiation; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena

Study Officials

• Jennifer Johnson, MD, PhD

  Sidney Kimmel Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 11, 2014
• First Posted: December 17, 2014
• Study Start: February 5, 2015
• Primary Completion: June 5, 2018
• Study Completion: March 25, 2021
• Last Updated: May 15, 2025

Record last verified: 2025-05

Locations

US (1)