Vemurafenib Plus Copanlisib in Radioiodine-Refractory (RAIR) Thyroid Cancers
A Phase Ib Trial of Vemurafenib Plus Copanlisib to Enhance Radioiodine Avidity in Radioiodine-Refractory Thyroid Cancers
1 other identifier
interventional
8
1 country
7
Brief Summary
The purpose of this study is to develop a new drug treatment to reverse tumor resistance to radioiodine in BRAF mutant tumors so that radioiodine can be given to shrink tumors. This study is also being done to find out the highest doses of copanlisib and vemurafenib that, when given in combination, do not cause serious side effects, and whether the study treatment will make radioiodine therapy work better in patients with BRAF-mutant thyroid cancers.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jun 2020
Typical duration for phase_1
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 26, 2020
CompletedFirst Submitted
Initial submission to the registry
July 2, 2020
CompletedFirst Posted
Study publicly available on registry
July 8, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 29, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
September 29, 2023
CompletedResults Posted
Study results publicly available
February 28, 2025
CompletedSeptember 8, 2025
August 1, 2025
3.3 years
July 2, 2020
September 13, 2024
August 26, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
The primary objective of this study is to determine the MTD of vemurafenib plus copanlisib inpatients with advanced BRAF mutant RAIR thyroid cancer. The MTD is defined as the highest dose at which no more than 1 of 6 patients treated at that dose experience a DLT.
6 months
Study Arms (1)
Participants with thyroid cancer
EXPERIMENTALEligible participants will have a diagnosis of BRAF mutant RAIR thyroid cancer
Interventions
I-124 PET/CT scans will be performed during this process to quantify baseline RAI avidity in index metastatic lesion(s)
Dose level 1 \& 2: 960 mg PO bid Dose level -1: 720 mg PO bid Dose level -2: 480 mg PO bid
Dose level 2: 60 mg IV weekly Dose level 1, -1, -2: 45 mg IV weekly
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed thyroid carcinoma of follicular origin (including papillary, follicular, and poorly differentiated subtypes and their respective variants).
- A tumor sample (primary, recurrent, or metastatic tumors) possessing a BRAF V600 mutation, as confirmed in a CLIA-certified laboratory or using an FDA-approved assay
- Measurable disease by RECIST v1.1 (tumors in previously irradiated fields may be considered measurable if there is evidence of tumor progression after radiation treatment)
- RAIR disease, as defined by any one of the following:
- A metastatic lesion that is not RAI-avid on a diagnostic radioiodine scan
- An RAI-avid lesion that remained stable in size or progressed despite RAI treatment before entry in this study (there are no size limitations for the index lesion used to satisfy this entry criterion)
- The presence of at least 1 FDG-avid lesion
- No receipt of treatment for thyroid cancer, defined as:
- No I-131 therapy \< 6 months before initiation of the protocol (time of initiation of the protocol is defined as the first day of drug therapy with vemurafenib and copanlisib); diagnostic activities of I-131 (0-10m Ci) are allowed within 6months of initiating the protocol
- No external beam radiation therapy \<4 weeks before initiation of the protocol
- No chemotherapy or targeted therapy including TKIs \<4 weeks (or \<5 half lives of the drug) before the initiation of this protocol
- Age of ≥ 18 years
- ECOG performance status ≤ 2 or Karnofsky Performance Score (KPS) ≥ 70%
- Tissue from the primary tumor or metastases available for correlative studies. Either a paraffin block or at least 20 unstained slides are acceptable (30 unstained slides is ideal); if \<20 unstained slides are available, and a paraffin block is not available, the patient may be able to participate at the discretion of the investigator
- Able to swallow and retain an orally administered pill without any clinically significant gastrointestinal abnormalities that may alter absorption, such as malabsorption syndrome or major resection of the stomach or bowels
- +12 more criteria
You may not qualify if:
- Untreated metastatic brain or leptomeningeal tumors (metastatic brain or leptomeningeal tumors treated with radiation and/or surgery are allowed)
- Prior malignancy if diagnosed and treated within 2 years of trial drug initiation (with the exception of nonmelanoma skin cancers or Stage I cancers treated with curative intent).Patients may be included if they have completed therapy for a prior malignancy \>2 years before drug initiation and currently have no evidence of disease
- Inability to follow a low-iodine diet or requiring a medication with a high content of iodide (amiodarone)
- Current congestive heart failure class \>2, as defined by the New York Heart Association functional classification system
- Myocardial infarction \< 6 months before the initiation of protocol
- Unstable angina (angina symptoms at rest) or new-onset angina (begun within the last 3 months)
- Uncontrolled hypertension (blood pressure \>150/90, despite optimal medical management)
- Uncontrolled type I or II diabetes mellitus, as judged by the investigator, or Hgb A1C of \>8.5
- Arterial or venous thrombotic event or embolic event, such as a cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism, within 3 months before the start of study medication
- Nonhealing wound, ulcer, or bone fracture (tumor-related nonhealing wounds are allowed)
- Active, clinically serious infections CTCAE v5.0 grade \>2
- History of concurrent condition of interstitial lung disease and/or severely impaired lung function
- Known history of HIV infection (all patients must be screened for HIV up to 28 days before start of study)
- Seizure disorder requiring medication
- Therapy with a prohibited concomitant medication that cannot be temporarily held (at least 2 weeks before initiation of vemurafenib plus copanlisib until 1 week after the last dose) or replaced with a nonprohibited concomitant medication
- +14 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
Memorial Sloan Kettering Monmouth (Limited protocol activities)
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Cancer Center @ Commack (Limited Protocol Activities)
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester (Limited protocol activities)
Harrison, New York, 10604, United States
Memorial Sloan-Kettering Cancer Center (All protocol activities)
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau (Limited protocol activities)
Rockville Centre, New York, 11553, United States
Related Publications (1)
Mauguen A, Grewal RK, Augensen F, Abusamra M, Mahajan S, Jayaprakasam VS, Osborne J, Haque S, Wong BZY, Ghossein RA, Fagin J, Schӧder H, Tuttle RM, Ho A, Humm JL, Larson SM. The use of single-timepoint images to link administered radioiodine activity (MBq) to a prescribed lesion radiation-absorbed dose (cGy): a regression-based prediction interval tool for the management of well-differentiated thyroid cancer patients. Eur J Nucl Med Mol Imaging. 2023 Aug;50(10):2971-2983. doi: 10.1007/s00259-023-06240-1. Epub 2023 May 12.
PMID: 37171634DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Alan Ho, MD, PhD
- Organization
- Memorial Sloan Kettering Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Alan L Ho, MD, PhD
Memorial Sloan Kettering Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 2, 2020
First Posted
July 8, 2020
Study Start
June 26, 2020
Primary Completion
September 29, 2023
Study Completion
September 29, 2023
Last Updated
September 8, 2025
Results First Posted
February 28, 2025
Record last verified: 2025-08
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.