NCT04544111

Brief Summary

The purpose of this study is to find out whether a drug called PDR001, combined with either trametinib or dabrafenib, is a safe and effective treatment for thyroid cancer.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
19

participants targeted

Target at below P25 for phase_2

Timeline
4mo left

Started Sep 2020

Longer than P75 for phase_2

Geographic Reach
1 country

7 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress95%
Sep 2020Sep 2026

Study Start

First participant enrolled

September 2, 2020

Completed
1 day until next milestone

First Submitted

Initial submission to the registry

September 3, 2020

Completed
7 days until next milestone

First Posted

Study publicly available on registry

September 10, 2020

Completed
6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 2, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 2, 2026

Last Updated

October 7, 2025

Status Verified

October 1, 2025

Enrollment Period

6 years

First QC Date

September 3, 2020

Last Update Submit

October 6, 2025

Conditions

Thyroid CancerThyroid Cancer, FollicularPapillary Thyroid CancerFollicular Thyroid CancerHurthle Cell TumorPoorly Differentiated Thyroid Gland CarcinomaHurthle Cell Thyroid Neoplasia

Keywords

Thyroid CancerPDR001Radioiodine-Refractory Thyroid CancerMemorial Sloan Kettering Cancer Center20-258

Outcome Measures

Primary Outcomes (1)

  • Overall response rate

    The primary endpoint is to determine the overall response rate (ORR=CR+PR) as documented by RECIST v1.1 criteria within each cohort.

    1 year

Study Arms (2)

Cohort A-BRAF WT tumors

EXPERIMENTAL

Cohort A (BRAF WT tumors): trametinib (T) 2mg by mouth daily plus PDR001 400mg IV every 4 weeks

Drug: TrametinibDrug: PDR001

Cohort B-BRAF Mutant

EXPERIMENTAL

Cohort B (BRAF Mutant, resistant to previous BRAF inhibitors): dabrafenib (D) 150 mg twice daily (OR at dose the patient previously tolerated) plus PDR001 400mg IV every 4 weeks.

Drug: DabrafenibDrug: PDR001

Interventions

TrametinibDRUG

2mg by mouth daily \*If patient loses the ability to swallow while on study, trametinib may be provided as a powder in bottle for reconsititution. Trametinib, as a powder in bottle, will be mixed with sterile/purified water into an oral solution and administered PO or through enteral feeding tube

Cohort A-BRAF WT tumors
DabrafenibDRUG

150 mg twice daily (OR at dose the patient previously tolerated)

Cohort B-BRAF Mutant
PDR001DRUG

400mg IV every 4 weeks

Cohort A-BRAF WT tumorsCohort B-BRAF Mutant

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Cohort A Only: Confirmation in a CLIA certified laboratory that one of the patient's thyroid tumors (primary tumor, recurrent tumor, or metastases) does not possess a BRAFV600- mutation (non-V600- BRAF mutations, including BRAF translocations, may be included in this cohort).
  • Cohort A Only: Evidence of progressive disease (e.g. presence of new or growing lesion(s) on radiologic imaging and/or new or worsening tumor-related symptoms) within 14 months of study enrollment
  • Cohort B Only: Confirmation in a CLIA certified laboratory that one of the patient's thyroid tumors (primary tumor, recurrent tumor, or metastases) possesses a BRAFV600- mutation (e.g. V600E, V600K, V600D).
  • Cohort B Only: Patients must have documented progression (evidence of tumor growth or appearance of new tumor) on prior BRAF directed therapy (e.g. (but not limited to) vemurafenib, dabrafenib) and must have tolerated this therapy without \> Grade 3 toxicity on their most recent evaluation (excluding Grade 4 asymptomatic laboratory abnormalities).
  • Patients must have pathologically or cytologically confirmed differentiated thyroid cancer of follicular origin (including papillary thyroid carcinoma, follicular thyroid carcinoma, hurthle cell carcinomas, poorly differentiated thyroid carcinoma and their respective variants).
  • Patients must have RECIST v1.1 measurable disease.
  • Patients must have recurrent or metastatic disease not amenable to curative surgery or radiation.
  • Age \> 18 years.
  • ECOG performance status of 0 or 1.
  • Patients must have no recent treatment for thyroid cancer as defined as:
  • No prior RAI therapy is allowed \<6 months prior to initiation of therapy on this protocol. A diagnostic study using \<10 mCi of RAI is not considered RAI therapy
  • No external beam radiation therapy \<4weeks prior to initiation of therapy on this protocol.
  • No chemotherapy or targeted therapy (e.g., tyrosine kinase inhibitor) is allowed \<4 weeks prior to the initiation of therapy on this protocol (an exception to this are patients on dabrafenib who will be enrolling into Cohort B). Dabrafenib may be continued prior to and through trial enrollment into the start of the study therapy when PDR001 will be added to dabrafenib
  • RAI-refractory disease on structural imaging, defined as one of the following:
  • Total lifetime dose of radioiodine \> 600 mCi
  • +17 more criteria

You may not qualify if:

  • Cohort A Only:
  • Patients with the following ophthalmological finding/conditions:
  • Intraocular pressure \>21 mmHg, or uncontrolled glaucoma (irrespective of intraocular pressure).
  • Current or past history of central serous retinopathy or retinal vein occlusion.
  • Cohort A Only: Prior therapy with a MEK 1/2 targeted drug (with the exception of patients who received this therapy for a defined period of time to enhance radioiodine activity).
  • Symptomatic metastatic brain or leptomeningeal tumors (asymptomatic or treated metastatic brain or leptomeningeal tumors are allowed).
  • Prior therapy directed at the PD1/PD-L1 axis.
  • Any of the following cardiovascular risks:
  • A QT interval corrected for heart rate using the Bazett's formula QTcB ≥ 480 msec.
  • Clinically significant uncontrolled arrhythmias (Exception: patients with controlled atrial fibrillation for \>30 days prior to enrollment are eligible).
  • Acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months of enrollment.
  • ≥ Class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system.
  • Treatment-refractory hypertension defined as a blood pressure of systolic \>140 mmHg and/or diastolic \>90 mmHg which cannot be controlled by anti-hypertensive therapy.
  • Prior malignancy if treated within 2 years of trial drug initiation (with the exception of non-melanoma skin cancers). Patients may be included if they have completed therapy for a prior malignancy \>2 years prior to drug initiation and are currently NED.
  • Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.
  • +15 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited protocol activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited protocol activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited protocol activities)

Rockville Centre, New York, 11553, United States

Location

Related Links

MeSH Terms

Conditions

Thyroid NeoplasmsThyroid cancer, follicularThyroid Cancer, PapillaryAdenocarcinoma, FollicularAdenoma, OxyphilicThyroid cancer, Hurthle cell

Interventions

trametinibdabrafenibspartalizumab

Condition Hierarchy (Ancestors)

Endocrine Gland NeoplasmsNeoplasms by SiteNeoplasmsHead and Neck NeoplasmsEndocrine System DiseasesThyroid DiseasesAdenocarcinoma, PapillaryAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeAdenoma

Study Officials

  • Alan L Ho, MD, PhD

    Memorial Sloan Kettering Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 3, 2020

First Posted

September 10, 2020

Study Start

September 2, 2020

Primary Completion (Estimated)

September 2, 2026

Study Completion (Estimated)

September 2, 2026

Last Updated

October 7, 2025

Record last verified: 2025-10

Data Sharing

IPD Sharing
Will share

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Locations

US(7)