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Thyroid CarcinomaPhase 1NCT04462471

Vemurafenib Plus Copanlisib in Radioiodine-Refractory (RAIR) Thyroid Cancers

A Phase 1 study testing I-124 PET/CT lesion dosimetry, Vemurafenib and Copanlisib in people with Thyroid Carcinoma and Thyroid Cancer, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
I-124 PET/CT lesion dosimetry, Vemurafenib and Copanlisib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
7 sitesUnited States
Study dates
26 Jun 2020to 29 Sep 2023
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • Agree to undergo 2 research biopsies of (a) malignant lesion(s). Tumor tissue obtained before study consent or treatment can also be submitted in lieu of performance of the first pretreatment biopsy if the Principal Investigator deems it to be of sufficient quantity/quality/timeliness (tumor tissue obtained more than 3 years from time of study consent would not be eligible). Patients may be exempt from biopsy if (1) the investigator or person performing the biopsy judges that no tumor is accessible for biopsy, (2) the investigator or person performing the biopsy feels that the biopsy poses too great of a risk to the patient, or (3) the patient's platelet count is <100,000/mcL or the patient cannot be safely removed from anticoagulation therapy (if the anticoagulation therapy needs to be temporarily held for the biopsy procedure). If the investigator deems a second research biopsy to be high risk, the patient may be exempt from the second biopsy.
  • Screening laboratory values meeting the following criteria:
  • WBC ≥ 2000/µL
  • Neutrophils ≥ 1500/µL
  • Platelets ≥ 100 × 10^3/µL
  • Hemoglobin >9.0 g/dL
  • Lipase ≤ 1.5 × ULN
  • AST/ALT ≤ 3 × ULN
  • Total bilirubin ≤ 1.5 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin <3.0 mg/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 / 82 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

Who cannot join

  • 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)
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  • 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
  • Systemic corticosteroid therapy at a daily dose >15 mg prednisone or equivalent (previous corticosteroid therapy must be stopped or reduced to the allowed dose at least 7 days before study registration)
  • Cytomegalovirus (CMV) PCR-positive at baseline
  • Evidence or history of a bleeding diathesis or any hemorrhage or bleeding CTCAE v5.0 grade ≥ 3 within 4 weeks before the start of study protocol
  • HBV or HCV infection. All patients must be screened for HBV and HCV up to 28 days before the start of study medication using the routine hepatitis virus laboratorial panel. Patients positive for HBsAg or HBcAb will be eligible if they are negative for HBV-DNA (these patients should receive prophylactic HBV antiviral therapy). Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA
  • Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation
  • Substance abuse or medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  • Patients who are pregnant
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 6 months after the last administration of study treatment. Highly effective contraception methods include:
  • Total abstinence (when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before taking study treatment. In cases of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone-level assessment (FSH level in the postmenopausal range) is this acceptable
  • Male sterilization (at least 6 months before screening). The vasectomized male partner should be the sole partner for that patient
  • Use of oral, injected, or implanted hormonal methods of contraception or placement of an intrauterine device or intrauterine system or other forms of hormonal contraception that have comparable efficacy (failure rate <1%)-for example, hormone vaginal ring or transdermal hormone contraception. Note: In cases of use of oral contraception, women should have been stable, on the same pill for a minimum of 3 months before taking study treatment
  • Women are considered postmenopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks ago. In cases of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone-level assessment is she considered not of child-bearing potential.
  • Sexually active men, unless they use a condom during intercourse while on treatment and for 6 months after stopping treatment with study drugs (men should not father a child in this period). A condom is required to be used by vasectomized men as well during intercourse to prevent delivery of the drug via semen.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

    Basking Ridge, New Jersey, 07920

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

    Commack, New York, 11725

  • Memorial Sloan Kettering Westchester (Limited protocol activities)

    Harrison, New York, 10604

  • Memorial Sloan Kettering Monmouth (Limited protocol activities)

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Bergen (Limited Protocol Activities)

    Montvale, New Jersey, 07645

  • Memorial Sloan-Kettering Cancer Center (All protocol activities)

    New York, New York, 10065

  • Memorial Sloan Kettering Nassau (Limited protocol activities)

    Rockville Centre, New York, 11553

Other trials in United States

About this study

Official title: A Phase Ib Trial of Vemurafenib Plus Copanlisib to Enhance Radioiodine Avidity in Radioiodine-Refractory Thyroid Cancers

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.

Being tested
I-124 PET/CT lesion dosimetry, Vemurafenib, Copanlisib
Keywords
thyroid carcinoma of follicular origin, thyroid cancer, thyroid cancer, follicular, thyroid cancer, papillary, thyroid cancer, poorly differentiated, BRAF V600, RAIR disease, Memorial Sloan Kettering Cancer Center, 20-053
Medical subject headings
Thyroid Neoplasms, Thyroid cancer, follicular, Thyroid Cancer, Papillary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • I-124 PET/CT lesion dosimetryDiagnostic test

    I-124 PET/CT scans will be performed during this process to quantify baseline RAI avidity in index metastatic lesion(s)

  • VemurafenibDrug

    Dose level 1 \& 2: 960 mg PO bid Dose level -1: 720 mg PO bid Dose level -2: 480 mg PO bid

  • CopanlisibDrug

    Dose level 2: 60 mg IV weekly Dose level 1, -1, -2: 45 mg IV weekly

Study groups in NCT04462471
Study groupRoleWhat they receive
Participants with thyroid cancerExperimentalEligible participants will have a diagnosis of BRAF mutant RAIR thyroid cancer
Receives: Diagnostic Test: I-124 PET/CT lesion dosimetry; Drug: Vemurafenib; Drug: Copanlisib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jul 2020
  2. Study start26 Jun 2020
  3. Primary completion29 Sep 2023
  4. Study completion29 Sep 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04462471
Sponsor's protocol ID
20-053
Status last verified
Aug 2025
First submitted
2 Jul 2020
Last updated
8 Sep 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 37171634

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing I-124 PET/CT lesion dosimetry, Vemurafenib and Copanlisib in people with Thyroid Carcinoma and Thyroid Cancer, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04462471, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2025.

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