Thyroid CancerPhase 1NCT02456701
Enhancing Radioiodine Incorporation Into BRAF Mutant Thyroid Cancers With the Combination of Vemurafenib and KTN3379
A Phase 1 study testing KTN3379 and vemurafenib in people with Thyroid Cancer, run by Celldex Therapeutics at 1 site in United States.
Trial summary
This is a patient pilot study testing the hypothesis that vemurafenib with the addition of KTN3379 can restore iodine incorporation in BRAF mutant (MUT), radioiodine-refractory (RAIR) thyroid cancer patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thyroid Cancer
- What is being tested?
- KTN3379 and vemurafenib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2015to 13 Oct 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Patients must have histologically or cytologically confirmed thyroid carcinoma of follicular origin (including papillary, follicular, or poorly differentiated subtypes and their respective variants).
- Confirmation in a CLIA certified laboratory or in an FDA-approved assay that one of the patient's thyroid tumors (primary tumor, recurrent tumor, or metastasis) possesses a BRAF mutation at V600.
- Patients must have measurable disease defined by RECIST criteria 1.1.
- Tumors in previously irradiated fields may be considered measureable if there is evidence of tumor progression after radiation treatment.
- RAI-refractory disease on structural imaging
- Age ≥ 18 years.
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- ECOG performance status ≤ 2
- Patients must have normal organ and marrow function as defined below:
- Absolute neutrophil count (ANC) > 1500/mcl
- Hemoglobin ≥ 9 g/dL
- Platelets ≥ 100,000/mcl
- Albumin ≥ 2.5 g/dL
- Total bilirubin ≤ 1.5x institutional ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2x institutional ULN unless it is related to the primary disease
- Creatinine ≤ 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) ≥ 50 mL/min OR 24-hour urine creatinine clearance ≥ 50 mL/min
Who cannot join
- Concomitant malignancies or previous malignancies treated within the past 3 years. Exception: Patients who have been disease-free for 3 years, patients with a history of completely resected non-melanoma skin cancer, and/or patients with indolent secondary malignancies, are eligible.
- Use of other investigational drugs within 28 days preceding the first dose of vemurafenib on this study.
- Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression.
- History or evidence of cardiovascular risk including any of the following:
- Corrected QT (QTc) interval ≥ 450 msec at baseline or history of congenital long QT syndrome or uncorrectable electrolyte abnormalities. (Patients with well controlled atrial fibrillation are exempt from this criteria.)
- History of cerebrovascular attack or transient ischemic attack within 6 months prior to the initiation of therapy on this protocol.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
About this study
Official title: Enhancing Radioiodine (RAI) Incorporation Into BRAF Mutant, RAI Refractory Thyroid Cancers With the Combination of BRAF Inhibitor Vemurafenib and Anti-ErbB3 Antibody KTN3379: A Pilot Study With a Phase 1 Run-in
This is a patient pilot study testing the hypothesis that vemurafenib with the addition of KTN3379 can restore iodine incorporation in BRAF mutant (MUT), radioiodine-refractory (RAIR) thyroid cancer patients.
Read the detailed description
This is a patient pilot study testing the hypothesis that vemurafenib with the addition of KTN3379 can restore iodine incorporation in BRAF mutant (MUT), radioiodine-refractory (RAIR) thyroid cancer patients. Eligible patients with BRAF MUT, RAIR thyroid cancer will undergo human recombinant TSH (rhTSH or Thyrogen)-stimulated 124I PET/CT lesional dosimetry to quantify the baseline RAI avidity of index metastatic lesion(s). Patients will then receive vemurafenib followed by the addition of KTN3379 after which a second Thyrogen-stimulated 124I PET/CT lesional dosimetry will be performed. For patients whose tumor(s) demonstrate sufficient iodine incorporation warranting 131I therapy, Thyrogen-stimulated standard dosimetry will be performed and therapeutic 131I will be administered concurrently with vemurafenib and KTN3379. Subsequent to discontinuation of vemurafenib, tumor assessments will be conducted with serial radiologic scan(s) and thyroglobulins (scans will be performed at baseline, before 131I, 3 months (+/- 1 month) following 131I, and 6 months after 131I).
- Conditions
- Thyroid Cancer
- Being tested
- KTN3379, vemurafenib
- Keywords
- CDX3379
- Medical subject headings
- Thyroid Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KTN3379Biological
IV every 2 weeks
vemurafenibDrug
Also called Zelboraf
960 mg po bid
| Study group | Role | What they receive |
|---|---|---|
| Combination of Vemurafenib and KTN3379 | Experimental | Vemurafenib 960 mg po bid KTN3379 1000 mg IV q2weeks Receives: Biological: KTN3379; Drug: vemurafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of patients with BRAF MUT, radioiodine-refractory thyroid cancer in which the combination of vemurafenib and KTN3379 can increase tumoral iodine incorporation to warrant 131I treatment
Measured: 4 to 6 weeks
Secondary outcomes (1)
Safety and tolerability of the combination of vemurafenib and KTN3379 by assessing adverse events
Measured: 6 to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2015 (estimated)
- Study startJun 2015
- Primary completion13 Oct 2016
- Study completion13 Oct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Thyroid CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celldex Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Memorial Sloan Kettering Cancer Center
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02456701
- Sponsor's protocol ID
- KTN3379-CL-003
- Status last verified
- Aug 2017
- First submitted
- 20 May 2015
- Last updated
- 5 Sep 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Tchekmedyian V, Dunn L, Sherman E, Baxi SS, Grewal RK, Larson SM, Pentlow KS, Haque S, Tuttle RM, Sabra MM, Fish S, Boucai L, Walters J, Ghossein RA, Seshan VE, Knauf JA, Pfister DG, Fagin JA, Ho AL. Enhancing Radioiodine Incorporation in BRAF-Mutant, Radioiodine-Refractory Thyroid Cancers with Vemurafenib and the Anti-ErbB3 Monoclonal Antibody CDX-3379: Results of a Pilot Clinical Trial. Thyroid. 2022 Mar;32(3):273-282. doi: 10.1089/thy.2021.0565.
PubMed 35045748
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enhancing Radioiodine (RAI) Incorporation Into BRAF Mutant, RAI Refractory Thyroid Cancers With the Combination of BRAF Inhibitor Vemurafenib and Anti-ErbB3 Antibody KTN3379: A Pilot Study With a Phase 1 Run-in
- ClinicalTrials.gov ID
- NCT02456701
- Acronym / sponsor ID
- KTN3379-CL-003
- Conditions
- Thyroid Cancer
- Keywords
- CDX3379
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Celldex TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Memorial Sloan Kettering Cancer Center
- Study start
- Jun 2015
- Primary completion
- 13 Oct 2016 (actual)
- Study completion
- 13 Oct 2016 (actual)
- First posted
- 28 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a patient pilot study testing the hypothesis that vemurafenib with the addition of KTN3379 can restore iodine incorporation in BRAF mutant (MUT), radioiodine-refractory (RAIR) thyroid cancer patients.
Detailed description
This is a patient pilot study testing the hypothesis that vemurafenib with the addition of KTN3379 can restore iodine incorporation in BRAF mutant (MUT), radioiodine-refractory (RAIR) thyroid cancer patients. Eligible patients with BRAF MUT, RAIR thyroid cancer will undergo human recombinant TSH (rhTSH or Thyrogen)-stimulated 124I PET/CT lesional dosimetry to quantify the baseline RAI avidity of index metastatic lesion(s). Patients will then receive vemurafenib followed by the addition of KTN3379 after which a second Thyrogen-stimulated 124I PET/CT lesional dosimetry will be performed. For patients whose tumor(s) demonstrate sufficient iodine incorporation warranting 131I therapy, Thyrogen-stimulated standard dosimetry will be performed and therapeutic 131I will be administered concurrently with vemurafenib and KTN3379. Subsequent to discontinuation of vemurafenib, tumor assessments will be conducted with serial radiologic scan(s) and thyroglobulins (scans will be performed at baseline, before 131I, 3 months (+/- 1 month) following 131I, and 6 months after 131I).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination of Vemurafenib and KTN3379 | Experimental | Biological: KTN3379, Drug: vemurafenibVemurafenib 960 mg po bid KTN3379 1000 mg IV q2weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients must have histologically or cytologically confirmed thyroid carcinoma of follicular origin (including papillary, follicular, or poorly differentiated subtypes and their respective variants).
- Confirmation in a CLIA certified laboratory or in an FDA-approved assay that one of the patient's thyroid tumors (primary tumor, recurrent tumor, or metastasis) possesses a BRAF mutation at V600.
- Patients must have measurable disease defined by RECIST criteria 1.1.
- Tumors in previously irradiated fields may be considered measureable if there is evidence of tumor progression after radiation treatment.
- RAI-refractory disease on structural imaging
Key exclusion criteria (7 listed)
- Concomitant malignancies or previous malignancies treated within the past 3 years. Exception: Patients who have been disease-free for 3 years, patients with a history of completely resected non-melanoma skin cancer, and/or patients with indolent secondary malignancies, are eligible.
- Use of other investigational drugs within 28 days preceding the first dose of vemurafenib on this study.
- Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression.
- History or evidence of cardiovascular risk including any of the following:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KTN3379IV every 2 weeks | Biological | Combination of Vemurafenib and KTN3379 |
| vemurafenibAlso: Zelboraf960 mg po bid | Drug | Combination of Vemurafenib and KTN3379 |
Primary outcome
The number of patients with BRAF MUT, radioiodine-refractory thyroid cancer in which the combination of vemurafenib and KTN3379 can increase tumoral iodine incorporation to warrant 131I treatment
Time frame: 4 to 6 weeks
1 secondary outcome
Safety and tolerability of the combination of vemurafenib and KTN3379 by assessing adverse events
Time frame: 6 to 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2017.
- Derived from this study: PubMed 35045748Tchekmedyian V, Dunn L, Sherman E, Baxi SS, Grewal RK, Larson SM, Pentlow KS, Haque S, Tuttle RM, Sabra MM, Fish S, Boucai L, Walters J, Ghossein RA, Seshan VE, Knauf JA, Pfister DG, Fagin JA, Ho AL. Enhancing Radioiodine Incorporation in BRAF-Mutant, Radioiodine-Refractory Thyroid Cancers with Vemurafenib and the Anti-ErbB3 Monoclonal Antibody CDX-3379: Results of a Pilot Clinical Trial. Thyroid. 2022 Mar;32(3):273-282. doi: 10.1089/thy.2021.0565.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing KTN3379 and vemurafenib in people with Thyroid Cancer, run by Celldex Therapeutics at 1 site 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 15 inclusion and 7 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 5 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The number of patients with BRAF MUT, radioiodine-refractory thyroid cancer in which the combination of vemurafenib and KTN3379 can increase tumoral iodine incorporation to warrant 131I treatment (time frame: 4 to 6 weeks). 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 NCT02456701, 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 5 Sep 2017.