Nivolumab Plus Ipilimumab in Thyroid Cancer
- Registration Number
- NCT03246958
- Lead Sponsor
- 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™)
- 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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 53
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description DTC - Nivolumab alone for two weeks Nivolumab Differentiated Thyroid Cancer (DTC) participants received Ipilimumab 1mg/kg q6 weeks via IV infusion, starting two weeks after Nivolumab 3mg/kg q6 weeks. DTC - Nivolumab alone for two weeks Ipilimumab Differentiated Thyroid Cancer (DTC) participants received Ipilimumab 1mg/kg q6 weeks via IV infusion, starting two weeks after Nivolumab 3mg/kg q6 weeks. DTC - Ipilimumab alone for two weeks Nivolumab Differentiated Thyroid Cancer (DTC) participants received Nivolumab 3mg/kg q6 weeks via IV infusion, starting two weeks after Ipilimumab 1mg/kg q6 weeks. Differentiated Thyroid Cancer (Primary cohort) Nivolumab Differentiated Thyroid Cancer (DTC) participants received Ipilimumab (Ipi) 1mg/kg q6 weeks and Nivolumab (Nivo) 3mg/kg q6 weeks sequentially either Ipi or Nivo first with 2 weeks apart prior to start of either Ipi or Nivo second. Per protocol order in sequential design was not expected to impact efficacy rather was for exploratory correlative analyses. Participants were treated indefinitely until disease progression or withdrawal for other reasons. DTC - Ipilimumab alone for two weeks Ipilimumab Differentiated Thyroid Cancer (DTC) participants received Nivolumab 3mg/kg q6 weeks via IV infusion, starting two weeks after Ipilimumab 1mg/kg q6 weeks. Medullary Thyroid Cancer (Exploratory Cohort) Nivolumab Medullary Thyroid Cancer (MTC) participants received Ipilimumab (Ipi) 1mg/kg q6 weeks and Nivolumab (Nivo) 3mg/kg q6 weeks sequentially either Ipi or Nivo first with 2 weeks apart prior to start of either Ipi or Nivo second, or started Ipi or Nivo together. Per protocol order in sequential design was not expected to impact efficacy rather was for exploratory correlative analyses. Participants were treated indefinitely until disease progression or withdrawal for other reasons. Medullary Thyroid Cancer (Exploratory Cohort) Ipilimumab Medullary Thyroid Cancer (MTC) participants received Ipilimumab (Ipi) 1mg/kg q6 weeks and Nivolumab (Nivo) 3mg/kg q6 weeks sequentially either Ipi or Nivo first with 2 weeks apart prior to start of either Ipi or Nivo second, or started Ipi or Nivo together. Per protocol order in sequential design was not expected to impact efficacy rather was for exploratory correlative analyses. Participants were treated indefinitely until disease progression or withdrawal for other reasons. Anaplastic Thyroid Cancer (Exploratory Cohort) Ipilimumab Anaplastic Thyroid Cancer (ATC) participants received Ipilimumab (Ipi) 1mg/kg q6 weeks and Nivolumab (Nivo) 3mg/kg q6 weeks sequentially either Ipi or Nivo first with 2 weeks apart prior to start of either Ipi or Nivo second prior to study amendment or in combination from the start after study amendment due to aggressive nature of the disease in this cohort. Per protocol order in sequential design was not expected to impact efficacy rather was for exploratory correlative analyses. Participants were treated indefinitely until disease progression or withdrawal for other reasons. Differentiated Thyroid Cancer (Primary cohort) Ipilimumab Differentiated Thyroid Cancer (DTC) participants received Ipilimumab (Ipi) 1mg/kg q6 weeks and Nivolumab (Nivo) 3mg/kg q6 weeks sequentially either Ipi or Nivo first with 2 weeks apart prior to start of either Ipi or Nivo second. Per protocol order in sequential design was not expected to impact efficacy rather was for exploratory correlative analyses. Participants were treated indefinitely until disease progression or withdrawal for other reasons. MTC - Nivolumab alone for two week Nivolumab Medullary Thyroid Cancer (MTC)participants received Ipilimumab 1mg/kg q6 weeks via IV infusion, starting two weeks after Nivolumab 3mg/kg q6 weeks. MTC - Nivolumab alone for two week Ipilimumab Medullary Thyroid Cancer (MTC)participants received Ipilimumab 1mg/kg q6 weeks via IV infusion, starting two weeks after Nivolumab 3mg/kg q6 weeks. Anaplastic Thyroid Cancer (Exploratory Cohort) Nivolumab Anaplastic Thyroid Cancer (ATC) participants received Ipilimumab (Ipi) 1mg/kg q6 weeks and Nivolumab (Nivo) 3mg/kg q6 weeks sequentially either Ipi or Nivo first with 2 weeks apart prior to start of either Ipi or Nivo second prior to study amendment or in combination from the start after study amendment due to aggressive nature of the disease in this cohort. Per protocol order in sequential design was not expected to impact efficacy rather was for exploratory correlative analyses. Participants were treated indefinitely until disease progression or withdrawal for other reasons. MTC - Ipilimumab alone for two weeks Nivolumab Medullary Thyroid Cancer (MTC) participants received Nivolumab 3mg/kg q6 weeks via IV infusion, starting two weeks after Ipilimumab 1mg/kg q6 weeks. MTC - Ipilimumab alone for two weeks Ipilimumab Medullary Thyroid Cancer (MTC) participants received Nivolumab 3mg/kg q6 weeks via IV infusion, starting two weeks after Ipilimumab 1mg/kg q6 weeks. ATC - Nivolumab alone for two week Nivolumab Anaplastic Thyroid Cancer (ATC) received Ipilimumab 1mg/kg q6 weeks via IV infusion, starting two weeks after Nivolumab 3mg/kg q6 weeks. ATC - Ipilimumab alone for two week Nivolumab Anaplastic Thyroid Cancer (ATC) received Nivolumab 3mg/kg q6 weeks via IV infusion, starting two weeks after Ipilimumab 1mg/kg q6 weeks. ATC - Ipilimumab + Nivolumab Nivolumab Anaplastic Thyroid Cancer (ATC) received Nivolumab 3mg/kg q6 weeks and Ipilimumab 1mg/kg q6 weeks via IV infusion. ATC - Nivolumab alone for two week Ipilimumab Anaplastic Thyroid Cancer (ATC) received Ipilimumab 1mg/kg q6 weeks via IV infusion, starting two weeks after Nivolumab 3mg/kg q6 weeks. ATC - Ipilimumab alone for two week Ipilimumab Anaplastic Thyroid Cancer (ATC) received Nivolumab 3mg/kg q6 weeks via IV infusion, starting two weeks after Ipilimumab 1mg/kg q6 weeks. ATC - Ipilimumab + Nivolumab Ipilimumab Anaplastic Thyroid Cancer (ATC) received Nivolumab 3mg/kg q6 weeks and Ipilimumab 1mg/kg q6 weeks via IV infusion.
- Primary Outcome Measures
Name Time Method Best Overall Response Rate Median (range) treatment duration (days) of 163.0 (21.0-734.0) for DTC cohort, for MTC cohort was 58.0 (30.0-252.0), and for ATC cohort 135.5 (10.0-735.0). Best overall response rate is defined as the percentage of participants who achieved Complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
- Secondary Outcome Measures
Name Time Method Median Progression Free Survival Median (range) follow-up (months) for DTC cohort was 24.0 (1.84 - 24.7), for MTC cohort was 24.0 (23.0-24.2), and for ATC cohort was 22.2 (0.46 - 26.1). Progression-Free Survival (PFS) based on Kaplan-Meier methodology is defined as the time from randomization (or registration) to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation. Participants alive without PD were censored at the earliest of the date of the last disease evaluation or start of new anticancer therapy. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.
Overall Survival at 2 Years (OS2) Median (range) follow-up (months) for DTC cohort was 24.0 (1.84 - 24.7), for MTC cohort was 24.0 (23.0-24.2), and for ATC cohort was 22.2 (0.46 - 26.1). Overall Survival is the percent probability estimate at 2 years based on Kaplan-Meier methodology. OS is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive.
Treatment-Related Adverse Events Rate AEs were assessed every two weeks on treatment and within 30 days after the last dose. Median (range) treatment duration (days) of 163.0 (21.0-734.0) for DTC cohort, for MTC cohort was 58.0 (30.0-252.0), and for ATC cohort 135.5 (10.0-735.0). Treatment-related adverse events rate was defined as the proportion of participants who experienced an adverse event with treatment attribution of possible, probable or definite, including all grades based on the Common Toxicity Criteria for Adverse Events Version 4.0 (CTCAEv4) as reported on case report forms.
Trial Locations
- Locations (1)
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States