Clinical Trials /

Pembrolizumab in Anaplastic/Undifferentiated Thyroid Cancer

NCT02688608

Description:

This study is being done because there are currently no approved and no commonly working targeted therapies in anaplastic thyroid cancer (ATC). This is an area of urgent need for patients, not just for approved treatments but also rationally-designed clinical trials designed specifically for ATC. Patients diagnosed with anaplastic thyroid cancer have a very high likelihood of dying because of their disease. As such there is a clear need for improving therapy for ATC.

Related Conditions:
  • Thyroid Gland Undifferentiated (Anaplastic) Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Anaplastic/Undifferentiated Thyroid Cancer
  • Official Title: Phase II Trial of Pembrolizumab in Metastatic or Locally Advanced Anaplastic/ Undifferentiated Thyroid Cancer

Clinical Trial IDs

  • ORG STUDY ID: STU 012016-019
  • NCT ID: NCT02688608

Conditions

  • Anaplastic Thyroid Cancer

Interventions

DrugSynonymsArms
PembrolizumabKeytruda-MerckPembrolizumab

Purpose

This study is being done because there are currently no approved and no commonly working targeted therapies in anaplastic thyroid cancer (ATC). This is an area of urgent need for patients, not just for approved treatments but also rationally-designed clinical trials designed specifically for ATC. Patients diagnosed with anaplastic thyroid cancer have a very high likelihood of dying because of their disease. As such there is a clear need for improving therapy for ATC.

Detailed Description

      The goal of this multi-center, open-label trial is to measure the impact of treating
      metastatic anaplastic thyroid cancer patients with immune checkpoint therapy. This trial will
      potentially lead to the development of new therapy for anaplastic thyroid cancer. The drug to
      be administered, pembrolizumab is FDA approved with known side effects and is active in many
      tumor types.

      Programmed death 1 or (PD-1) PD-1/PD-L1 expression will be measured and reported for patients
      undergoing therapy with pembrolizumab. This will help determine if there PD-1 or PD-L1 are
      predictive biomarkers for anti-PD-1 therapy. It will also add to the data regarding their
      frequency in aggressive thyroid cancer. Where available, genomic profiling data will be
      analyzed to determine if there is a correlation between response and mutational status.
    

Trial Arms

NameTypeDescriptionInterventions
PembrolizumabExperimental200 milligrams of Pembrolizumab will be given intravenously every 3 weeks.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Be willing and able to provide written informed consent for the trial.

          2. Histologically or cytologically confirmed diagnosis of anaplastic thyroid cancer or
             undifferentiated thyroid cancer. A diagnosis of possible ATC/UTC will be allowed if
             the clinical presentation is consistent with anaplastic or undifferentiated thyroid
             cancer.

          3. Be ≥ 18 years of age on day of signing informed consent.

          4. Have measurable disease based on RECIST 1.1.

          5. Be willing to provide tissue from a newly obtained core or excisional biopsy of a
             tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days)
             prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples
             cannot be provided (e.g. inaccessible or subject safety concern) may submit an
             archived sample.

          6. Have a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale.

          7. Demonstrate adequate organ function as defined in the protocol. ,

          8. 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.

          9. 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.

         10. 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.

        Exclusion Criteria:

          1. 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.

          2. 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.

          3. Has a known history of active TB (Bacillus Tuberculosis).

          4. Hypersensitivity to pembrolizumab or any of its excipients.

          5. 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 adverse events
             due to agents administered more than 4 weeks earlier.

          6. 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.

               -  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.

          7. 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.

          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 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.

          9. 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.

         10. Has known history of, or any evidence of 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, or anti-PD-L2 agent.

         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 of planned start of study therapy. Note:
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
             attenuated vaccines, and are not allowed.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate of pembrolizumab
Time Frame:Every 3 weeks for up to 18 months.
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall survival in anaplastic thyroid cancer patients treated with pembrolizumab
Time Frame:Every 3 months for up to 18 months.
Safety Issue:
Description:
Measure:Adverse events associated with pembrolizumab
Time Frame:Every 3 months for up to 18 months.
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Texas Southwestern Medical Center

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