Nivolumab Plus Ipilimumab in Thyroid Cancer

Sponsor
Dana-Farber Cancer Institute (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03246958
Collaborator
Bristol-Myers Squibb (Industry)
53
Enrollment
1
Location
2
Arms
90.3
Anticipated Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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™)

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

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

Study Design

Study Type:
Interventional
Actual Enrollment :
53 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Sep 20, 2017
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Mar 31, 2025

Arms and Interventions

ArmIntervention/Treatment
Experimental: Nivolumab alone for two weeks

Ipilimumab will be administered via IV infusion, starting two weeks after Nivolumab

Drug: Nivolumab
Ipilimumab are types of immunotherapy Immunotherapy works by encouraging the body's own immune system to attack cancer cells.
Other Names:
  • Opdivo
  • Drug: Ipilimumab
    Nivolumab are types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack cancer cells.
    Other Names:
  • Yervoy
  • Experimental: Ipilimumab alone for two weeks

    Nivolumab will be administered via IV infusion, starting two weeks after Ipilimumab

    Drug: Nivolumab
    Ipilimumab are types of immunotherapy Immunotherapy works by encouraging the body's own immune system to attack cancer cells.
    Other Names:
  • Opdivo
  • Drug: Ipilimumab
    Nivolumab are types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack cancer cells.
    Other Names:
  • Yervoy
  • Outcome Measures

    Primary Outcome Measures

    1. Radiographic Response Rate [2 years]

      Radiographic Response Rate to the investigational treatment, as determined by RECIST v1.1 (PR+CR)

    Secondary Outcome Measures

    1. Progression Free Survival [2 years]

      The time from randomization to progression or death due to any cause

    2. Overall Survival [2 years]

      The time from randomization to death or date last known alive

    3. Tolerability [2 years]

      Treatment-Emergent Adverse Events (frequency and grade of adverse events)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Dana Farber Cancer InstituteBostonMassachusettsUnited States02215

    Sponsors and Collaborators

    • Dana-Farber Cancer Institute
    • Bristol-Myers Squibb

    Investigators

    • Principal Investigator: Kartik Sehgal, MD, Dana-Farber Cancer Institute

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Kartik Sehgal, Kartik Sehgal, MD, Dana-Farber Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT03246958
    Other Study ID Numbers:
    • 17-255
    First Posted:
    Aug 11, 2017
    Last Update Posted:
    Feb 22, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Kartik Sehgal, Kartik Sehgal, MD, Dana-Farber Cancer Institute
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 22, 2022