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Nivolumab Plus Ipilimumab in Thyroid Cancer

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03246958
Recruitment Status : Active, not recruiting
First Posted : August 11, 2017
Last Update Posted : August 18, 2020
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Jochen Lorch, MD, Dana-Farber Cancer Institute

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 disease Intervention/treatment Phase
Thyroid Cancer Drug: Nivolumab Drug: Ipilimumab 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

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Study Type : Interventional  (Clinical Trial)
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 : September 20, 2017
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : March 31, 2025


Arm Intervention/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 Name: Opdivo

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

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




Primary Outcome Measures :
  1. Radiographic Response Rate [ Time Frame: 2 years ]
    Radiographic Response Rate to the investigational treatment, as determined by RECIST v1.1 (PR+CR)


Secondary Outcome Measures :
  1. Progression Free Survival [ Time Frame: 2 years ]
    The time from randomization to progression or death due to any cause

  2. Overall Survival [ Time Frame: 2 years ]
    The time from randomization to death or date last known alive

  3. Tolerability [ Time Frame: 2 years ]
    Treatment-Emergent Adverse Events



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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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): NCT03246958


Locations
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United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Dana-Farber Cancer Institute
Bristol-Myers Squibb
Investigators
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Principal Investigator: Jochen Lorch, MD Dana-Farber Cancer Institute
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Responsible Party: Jochen Lorch, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT03246958    
Other Study ID Numbers: 17-255
First Posted: August 11, 2017    Key Record Dates
Last Update Posted: August 18, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jochen Lorch, MD, Dana-Farber Cancer Institute:
Thyroid Cancer
Additional relevant MeSH terms:
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Thyroid Neoplasms
Thyroid Diseases
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents