Nivolumab and Ipilimumab in Treating Patients with Metastatic or Refractory Thyroid Cancer
- Metastatic, radioactive iodine (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), medullary thyroid cancer, or anaplastic thyroid cancer; RAI-refractoriness is not required for medullary or anaplastic thyroid cancer patients; patients who are not candidates for RAI therapy, as determined by the investigator, are also eligible; 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.
- Patients must have experienced disease progression within 13 months prior to study registration, have experienced intolerable side effects on a tyrosine kinase inhibitor (TKI), or be not suitable candidates for TKI; no progression is required for patients with anaplastic thyroid cancer.
- Any number of prior treatments allowed for patients under 65 years (y), over 65y, if suitable candidate for TKI therapy, must have at least one prior line of TKI treatment (excluding medullary and anaplastic patients).
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%).
- Measurable disease by per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria; radiographic tumor assessment performed within 28 days of registration.
- White blood cell (WBC) >= 2000/uL (obtained within 21 days prior to randomization/registration).
- Neutrophils >= 1200/uL (obtained within 21 days prior to randomization/registration).
- Platelets >= 100 x 10^3/uL (obtained within 21 days prior to randomization/registration).
- Hemoglobin > 8.0 g/dL (obtained within 21 days prior to randomization/registration).
- Serum creatinine =< 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) >= 40 mL/min (if using the Cockcroft-Gault formula) (obtained within 21 days prior to randomization/registration).
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN (obtained within 21 days prior to randomization/registration).
- Total bilirubin =< 1.5 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL) (obtained within 21 days prior to randomization/registration).
- 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 human chorionic gonadotropin [HCG]) at screening. Pregnancy test will be repeated on the day of the first dose of study drug (before administration), although results of this test are not required for registration. * "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.
- 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 (i.e., who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception.
- 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.
- Diagnosed or treated for another malignancy within 2 years before administration of the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease; patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
- 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/radiotherapy and/or targeted agents within 2 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; for patients with anaplastic thyroid cancer or otherwise particularly aggressive disease (as determined by the investigator), the washout period for chemotherapy/radiotherapy and/or targeted agents will be at the investigator’s discretion.
- Patients who are receiving any other investigational agents.
- Patients with active brain 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.
I. To evaluate efficacy in terms of the radiographic response rate to the investigational treatment, as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 (partial response [PR]+complete response [CR]).
I. To evaluate progression-free survival (PFS).
II. To evaluate overall survival (OS).
III. To evaluate tolerability.
IV. To explore biomarkers through correlatives.
OUTLINE: Patients are randomized to 1 of 3 arms. Patients with anaplastic thyroid cancer are assigned to ARM III.
ARM I: Patients receive nivolumab intravenously (IV) over 60 minutes every 2 weeks and ipilimumab IV over 90 minutes every 6 weeks beginning in week 3. Cycles repeat every 6 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive ipilimumab IV over 90 minutes every 6 weeks and nivolumab IV over 60 minutes every 2 weeks beginning in week 3. Cycles repeat every 6 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.
ARM III: Patients receive ipilimumab IV over 90 minutes every 6 weeks and nivolumab IV over 60 minutes every 2 weeks. Cycles repeat every 6 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then for 2 years.
Trial Phase Phase II
Trial Type Treatment
Dana-Farber Harvard Cancer Center
Jochen Hanns-Martin Lorch
- Primary ID 17-255
- Secondary IDs NCI-2017-02341
- Clinicaltrials.gov ID NCT03246958