Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pembrolizumab and Radiation Therapy in Treating Patients With Intermediate or High-Grade Soft Tissue Sarcoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03338959
Recruitment Status : Recruiting
First Posted : November 9, 2017
Last Update Posted : May 29, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center

Brief Summary:
This pilot phase I/II trials studies pembrolizumab and radiation therapy in treating patients with intermediate or high-grade soft tissue sarcoma. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving pembrolizumab and radiation therapy may work better in treating patients with soft tissue sarcoma.

Condition or disease Intervention/treatment Phase
Soft Tissue Sarcoma Recurrent Soft Tissue Sarcoma Biological: Pembrolizumab Radiation: Radiation Therapy Phase 1 Phase 2

Detailed Description:

PRIMARY OBJECTIVE:

I. To determine the rate of complete histopathologic necrosis following the combination of pembrolizumab and neoadjuvant radiation.

SECONDARY OBJECTIVES:

I. To determine response based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria following the combination of radiation and pembrolizumab.

II. To confirm the tolerability and safety of the combination of neoadjuvant pembrolizumab and radiation in a population with localized soft tissue sarcoma (STS) based on Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) per institutional standard at the Seattle Cancer Care Alliance as an outpatient therapy. Cycles repeat every 3 weeks, up to a maximum of three doses, for 3 months in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy daily for 5-6 weeks beginning on Day 1 of Week 2.

After completion of study treatment, patients are followed up at 30 days after last dose, 90 days after last dose, 30 days after post-operative visit (wound care follow-up), and then every 12 weeks for up to 1 year, then every 6 months up to 5 years.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 26 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Pembrolizumab and Neoadjuvant Radiation for Large, High-Risk Soft Tissue Sarcomas
Actual Study Start Date : March 28, 2018
Estimated Primary Completion Date : December 1, 2021
Estimated Study Completion Date : June 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (pembrolizumab, radiation therapy)
Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks for 3 months in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy daily for 5-6 weeks.
Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • irradiation
  • Radiation
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
  • NOS




Primary Outcome Measures :
  1. Rate of complete tumor necrosis [ Time Frame: From baseline through wound care follow-up visit (up to 8 months) ]
    Percentage of the tumor that has undergone necrosis.


Secondary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Through the wound care follow-up visit (up to 8 months) ]
    Evaluated by Common Terminology Criteria for Adverse Events (CTCAE) 5.0.

  2. Partial Response Rate [ Time Frame: From baseline through wound care follow-up visit (up to 8 months) ]
    Proportion of patients who achieved a partial response (≥30% decrease in the sum of the longest diameters of target tumors) based on modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Be willing and able to provide written informed consent for the trial
  • Be ≥18 years of age on day of signing informed consent documents
  • Have measurable disease based on RECIST 1.1
  • Have newly diagnosed disease or localized recurrent or oligometastatic lesions that are candidates for radiation

    • NOTE: Subjects may not have any prior systemic therapy or radiation for this sarcoma. They may have received systemic therapy and/or radiation for a different cancer
    • NOTE: Oligometastatic disease will be defined as 3 or fewer detectable lesions with plans to radiate all detectable disease with conventionally fractionated radiation prior to resection
  • Have an intermediate- or high-grade soft tissue sarcoma according to the French Federation of Cancer Centers Sarcoma Group (Federation Nationale des Centres de Lutte Contre Le Cancer [FNCLCC]) criteria
  • The tumor must be at least 3 cm in maximum dimension for intermediate-grade tumors, or 1.5 cm in maximum dimension for high-grade tumors
  • Have plans to undergo neo-adjuvant radiation and surgery with curative intent. A minimum of 45 Gy is necessary, planned to be administered over a minimum of 25 fractions
  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Archival tissue from a recent clinical or Pollack Lab research biopsy (within the 4 weeks of beginning radiation treatment) may be used in place of a fresh tissue biopsy
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale or > 70% on the Karnofsky scale. Evaluation of performance status is to be performed within 7 days prior to the date of enrollment
  • Absolute neutrophil count (ANC) >= 1,500/mcL (performed within 28 days of enrollment)
  • Platelets >= 100,000/mcL (performed within 28 days of enrollment)
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (performed within 28 days of enrollment)

    * Criteria must be met without erythropoeiten dependency and without packed red blood cell (pRBC) transfusion within last two weeks

  • Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (performed within 28 days of enrollment)

    * Creatinine clearance should be calculated per institutional standard

  • Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (performed within 28 days of enrollment)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN (performed within 28 days of enrollment)
  • Albumin >= 2.5 mg/dL (performed within 28 days of enrollment)
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 28 days of enrollment)
  • 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 (performed within 28 days of enrollment)
  • Female subjects of childbearing potential should have a negative serum pregnancy within 72 hours prior to receiving the first dose of study medication
  • All individuals of child-bearing potential must be willing to use an adequate method of contraception, from the first dose of the study medication through 120 days after the last dose of study medication

Exclusion Criteria:

  • Has had prior radiation to affected area
  • Has one of the following sarcoma subtypes where neoadjuvant chemotherapy is established as practice at our institution: extra-skeletal Ewing's sarcoma, embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma

    * NOTE: Pleomorphic rhabdomyosarcoma is allowed. Bone sarcomas including osteosarcoma, Ewing's sarcoma and chondrosarcoma are not allowed

  • Has a diagnosis of immunodeficiency or has an 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
  • Has a known history of active TB (Bacillus tuberculosis)
  • Hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
  • Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years

    * NOTE: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in-situ cancers

  • Has current or a history of any distant metastatic disease (including brain)

    *NOTE: An isolated or oligo-metastatic regional recurrence may be allowed if all other criteria are met, curative attempt is being pursued

  • Has known history of (non-infectious) pneumonitis that required steroids, or has current evidence of pneumonitis
  • Has an active infection requiring systemic therapy
  • Has known psychiatric or substance abuse disorders that would interfere with adherence to the requirements of the trial
  • Is pregnant (positive urine pregnancy test within 72 hours prior to enrollment) 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. If a urine pregnancy test is positive or cannot be confirmed negative, a serum pregnancy test will be required
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-CTLA4 or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory 1-cell receptor (eg, CTLA-4, OX 40, CD137)
  • Has a known history of human immunodeficiency virus (HIV) infection
  • Has a known history of Hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or Hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) infection
  • Has received a live vaccine within 30 days of planned start of study therapy. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has had an allogenic tissue/solid organ transplant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03338959


Contacts
Layout table for location contacts
Contact: Roxanne Moore 206-606-6425 romoore@seattlecca.org

Locations
Layout table for location information
United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Roxanne Moore    206-606-6425    romoore@seattlecca.org   
Principal Investigator: Seth M. Pollack         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Principal Investigator: Seth Pollack Fred Hutch/University of Washington Cancer Consortium
Layout table for additonal information
Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT03338959    
Other Study ID Numbers: 9661
NCI-2017-01933 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
9661 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
RG9217020 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
First Posted: November 9, 2017    Key Record Dates
Last Update Posted: May 29, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents