Clinical Trials /

Nivolumab Plus Ipilimumab in Thyroid Cancer

NCT03246958

Description:

This research study is studying nivolumab, an investigational drug, in combination with ipilimumab, also an investigational drug, as a possible treatment for thyroid cancer. The drugs involved in this study are: - Nivolumab (Opdivo™) - Ipilimumab (Yervoy™)

Related Conditions:
  • Poorly Differentiated Thyroid Gland Carcinoma
  • Well-Differentiated Thyroid Gland Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab Plus Ipilimumab in Thyroid Cancer
  • Official Title: A Phase 2 Study of Nivolumab Plus Ipilimumab in RAI Refractory, Aggressive Thyroid Cancer With Exploratory Cohorts in Medullary and Anaplastic Thyroid Cancer

Clinical Trial IDs

  • ORG STUDY ID: 17-255
  • NCT ID: NCT03246958

Conditions

  • Thyroid Cancer

Interventions

DrugSynonymsArms
NivolumabOpdivoNivolumab alone for two weeks
IpilimumabYervoyNivolumab alone for two weeks

Purpose

This research study is studying nivolumab, an investigational drug, in combination with ipilimumab, also an investigational drug, as a possible treatment for thyroid cancer. The drugs involved in this study are: - Nivolumab (Opdivo™) - Ipilimumab (Yervoy™)

Detailed Description

      This research study is a Phase 2 clinical trial. Phase 2 clinical trials test the safety and
      effectiveness of an investigational intervention to learn whether the intervention works in
      treating a specific disease. "Investigational" means that the intervention is being studied.

      The purpose of this study is to evaluate effectiveness (how well the drug/s work) of
      nivolumab combined with ipilimumab.

      Nivolumab and ipilimumab are types of immunotherapy. Immunotherapy works by encouraging the
      body's own immune system to attack cancer cells. Nivolumab has been approved by the US Food
      and Drug Administration (FDA) for the treatment of metastatic melanoma (a type of skin
      cancer), and specific types of previously treated advanced lung and kidney cancers.
      Ipilimumab is approved by the FDA for the treatment of metastatic melanoma.

      The combination of nivolumab and ipilimumab is now FDA approved as treatment for patients
      with metastatic melanoma. However, the use of nivolumab as well as ipilimumab alone or in
      combination for the treatment of patients with thyroid cancer is not approved
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab alone for two weeksExperimentalIpilimumab will be administered via IV infusion, starting two weeks after Nivolumab
  • Nivolumab
  • Ipilimumab
Ipilimumab alone for two weeksExperimentalNivolumab will be administered via IV infusion, starting two weeks after Ipilimumab
  • Nivolumab
  • Ipilimumab

Eligibility Criteria

        Inclusion

          -  Metastatic, RAI refractory, differentiated thyroid cancer (including papillary and
             follicular thyroid cancer and their sub-types such as Hurthle cell thyroid cancer as
             well as poorly differentiated thyroid cancer), with progression within 13 months prior
             to study registration. RAI refractoriness is defined as absence of uptake of RAI on
             either a low-dose diagnostic test or a post-treatment RAI scan in measurable lesions
             or radiographic progression of disease within 12 months of the last course of RAI
             treatment despite the recorded uptake of RAI with that previous therapy or having a
             cumulative lifetime administered dose of greater than 600mCi.

          -  Exploratory cohort: incurable medullary thyroid cancer with prior tyrosine kinase
             inhibitor (TKI) failure and progression within 13 months prior to enrollment (10
             patients) and anaplastic thyroid cancer (7 patients)

          -  Any number of lines of prior treatment are allowed

          -  Any line of prior treatment for patients under 65y, over 65y must have at least one
             prior line of TKI treatment

          -  Age 18 years or older

          -  ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)

          -  Participants must have normal organ and marrow function as defined below:

          -  Screening laboratory values must meet the following criteria and should be obtained
             within 21 days prior to randomization/registration

               -  WBC ≥ 2000/μL

               -  Neutrophils ≥ 1500/μL

               -  Platelets ≥ 100 x103/μL

               -  Hemoglobin > 9.0 g/dL

               -  Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using
                  the Cockcroft-Gault formula below):

               -  Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in
                  mg/dL

               -  Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in
                  mg/dL

               -  AST/ALT ≤ 3 x ULN

               -  Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have
                  total bilirubin < 3.0 mg/dL)

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Women of childbearing potential (WOCBP) must use appropriate method(s) of
             contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30
             days plus the time required for nivolumab to undergo five half-lives) after the last
             dose of investigational drug

          -  Women of childbearing potential must have a negative serum or urine pregnancy test
             (minimum sensitivity 25 iu/l or equivalent units of hcg) within 24 hours of the first
             dose of the study drug

          -  Women of childbearing potential" is defined as any female who has experienced menarche
             and who has not undergone surgical sterilization (hysterectomy or bilateral
             oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12
             months of amenorrhea in a woman over 45 in the absence of other biological or
             physiological causes. In addition, women under the age of 55 must have a documented
             serum follicle stimulating hormone (FSH) level less than 40 mIU/mL.

          -  Men who are sexually active with WOCBP must use any contraceptive method with a
             failure rate of less than 1% per year Men receiving nivolumab and who are sexually
             active with WOCBP will be instructed to adhere to contraception for a period of 31
             weeks after the last dose of investigational product Women who are not of childbearing
             potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men
             do not require contraception

        Exclusion

          -  Patients should be excluded if they have an active, known or suspected autoimmune
             disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes
             mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone
             replacement, psoriasis not requiring systemic treatment, or conditions not expected to
             recur in the absence of an external trigger

          -  Patients should be excluded if they have a condition requiring systemic treatment with
             either corticosteroids (> 10 mg daily prednisone equivalents) or other
             immunosuppressive medications within 14 days of study drug administration. Inhaled or
             topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents
             are permitted in the absence of active autoimmune disease.

          -  As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab
             combinations, drugs with a predisposition to hepatoxicity should be used with caution
             in patients treated with nivolumab-containing regimen.

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier.

          -  Patients who are receiving any other investigational agents.

          -  Patients with activebrain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Radiographic Response Rate
Time Frame:2 years
Safety Issue:
Description:Radiographic Response Rate to the investigational treatment, as determined by RECIST v1.1 (PR+CR)

Secondary Outcome Measures

Measure:Progression Free Survival
Time Frame:2 years
Safety Issue:
Description:The time from randomization to progression or death due to any cause
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:The time from randomization to death or date last known alive
Measure:Tolerability
Time Frame:2 years
Safety Issue:
Description:Treatment-Emergent Adverse Events

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Thyroid Cancer

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