NeoplasmsPhase 2NCT01286753
A Study of Vemurafenib (RO5185426) in Participants With Metastatic or Unresectable Papillary Thyroid Cancer Positive for the BRAF V600 Mutation
A Phase 2 study testing Vemurafenib in people with Neoplasms, run by Hoffmann-La Roche at 16 sites in 4 countries.
Trial summary
This open-label, multi-center study will evaluate the safety and efficacy of Vemurafenib (RO5185426) in participants with metastatic or unresectable papillary thyroid cancer (PTC) positive for the BRAF V600 mutation and resistant to radioactive iodine therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- Vemurafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 16 sitesin 4 countries
- Study dates
- Jun 2011to May 2015
- Phase
- Phase 2
- 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
- Adult participants. >/= 18 years of age
- Histologically confirmed metastatic or unresectable papillary thyroid cancer for which standard curative or palliative measures do not exist or are no longer effective; participants whose tumors exhibit areas of "other histology" may be enrolled, provided the tumor histology remains predominantly papillary
- Positive for BRAF V600 mutation (Roche Cobas 4800 BRAF V600 Mutation Test)
- Radioactive Iodine resistant disease
- Prior therapy excluding (Cohort 1, TKI Naive) or including (Cohort 2, TKI Experienced) TKI
- Clinically relevant disease progression according to RECIST criteria within the prior 14 months
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Adequate hematological, renal and liver function
Who cannot join
- Histological diagnosis other than papillary PTC, including squamous cell variants of PTC or PTC with areas of squamous metaplasia
- Active or untreated central nervous system metastases
- History of or known carcinomatous meningitis
- Anticipated or ongoing administration of any anti-cancer therapies other than those administered in the study
- Active squamous cell skin cancer that has not been excised or adequately healed post excision
- Previous treatment with any agent that specifically and selectively targets the MEK or BRAF pathway
- Prior radiotherapy to the only measurable lesion
- Clinically relevant cardio-vascular disease or event within the prior 6 months
Trial locations and contacts
16 sites in 4 countries.
16 sites in 4 countries
United States9 sites
Study site
Baltimore, Maryland, 21231
Study site
Boston, Massachusetts, 02114
Study site
Boston, Massachusetts, 02215
Study site
Chicago, Illinois, 60637
Study site
Houston, Texas, 77030
Study site
New Haven, Connecticut, 06510
Study site
New York, New York, 10017
Study site
Philadelphia, Pennsylvania, 19104
Study site
Torrance, California, 90502
France3 sites
Study site
Lyon, 69008
Study site
Paris, 75651
Study site
Villejuif, 94805
Netherlands2 sites
Study site
Groningen, 9700 RB
Study site
Leiden, 2300 RC
About this study
Official title: An Open-Label, Multi-Center Phase II Study of the BRAF Inhibitor Vemurafenib in Patients With Metastatic or Unresectable Papillary Thyroid Cancer (PTC) Positive for the BRAF V600 Mutation and Resistant to Radioactive Iodine
This open-label, multi-center study will evaluate the safety and efficacy of Vemurafenib (RO5185426) in participants with metastatic or unresectable papillary thyroid cancer (PTC) positive for the BRAF V600 mutation and resistant to radioactive iodine therapy. Participants will receive vemurafenib 960 milligrams (mg) orally twice daily until progressive disease or unacceptable toxicity occurs.
- Conditions
- Neoplasms
- Being tested
- Vemurafenib
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VemurafenibDrug
Also called Zelboraf®, RO5185426
Vemurafenib 960 mg orally twice daily.
| Study group | Role | What they receive |
|---|---|---|
| Tyrosine Kinase Inhibitor (TKI) Naive | Experimental | Vemurafenib in participants naive to any prior systemic TKI therapy. Receives: Drug: Vemurafenib |
| TKI Experienced | Experimental | Vemurafenib in participants previously treated with TKI therapy active against vascular endothelial growth factor receptor 2 (VEGFR). Receives: Drug: Vemurafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Overall Response Rate in TKI-Naive Participants
Best overall response rate was assessed by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Best overall response rate: the percentage of participants with best objective response of complete response (CR) or partial response (PR) (calculated as the number of participants with best response CR or PR divided by the total number of efficacy-evaluable participants). CR: disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to < 10 millimeters (mm). PR: ≥ 30% decrease in the sum of diameters of target lesions, compared to the baseline sum diameters.
Measured: Up to approximately 4 years
Secondary outcomes (7)
Best Overall Response Rate in TKI-Experienced Participants
Best overall response rate was assessed by the investigators according to RECIST v1.1. Best overall response rate: the percentage of participants with best objective response of CR or PR (calculated as the number of participants with best response CR or PR divided by the total number of efficacy-evaluable participants). CR: disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to < 10 mm. PR: ≥ 30% decrease in the sum of diameters of target lesions, compared to the baseline sum diameters.
Measured: Up to approximately 4 years
Clinical Benefit Rate
Clinical benefit rate: the percentage of participants with confirmed CR, PR, or stable disease (SD; maintained for at least 6 months) as assessed by investigators according to RECIST v1.1. CR: disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to < 10 mm. PR: ≥ 30% decrease in the sum of diameters of target lesions, compared to the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, compared to the baseline sum diameters.
Measured: Up to approximately 4 years
Duration of Response
Duration of response (for participants with confirmed best response CR or PR): the interval between earliest qualifying response and date of progression of disease (PD) or death for any cause, whichever occurred first; participants with no documented progression after CR or PR were censored at the date of last known CR or PR, respectively. CR: disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to < 10 mm. PR: ≥ 30% decrease in the sum of diameters of target lesions, compared to the baseline sum diameters. PD: ≥ 20% increase in the sum of diameters of target lesions, compared to the smallest sum on study.
Measured: From the date of first qualifying response to the date of PD or death for any cause (up to approximately 4 years)
Progression-Free Survival
Progression-free survival: the interval between the day of first treatment and the first documentation of PD or death; participants who were withdrawn from the study without documented progression were censored at the date of the last tumor assessment when the participant was known to be progression-free; participants without post baseline tumor assessments were censored at the time of enrollment. PD: ≥ 20% increase in the sum of diameters of target lesions, compared to the smallest sum on study.
Measured: From the day of first treatment until the first documented PD or death (up to approximately 4 years)
Overall Survival
Overall survival: the interval between the date of first treatment to the date of death, regardless of the cause of death; participants who were alive at the time of the analysis were censored at the date of the last known alive; participants with no post baseline information were censored at the time of enrollment.
Measured: From the date of first treatment to the date of death for any cause (up to approximately 4 years)
Percentage of Participants With Adverse Events
An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Measured: Baseline until 28 days after the last dose of study treatment or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 4 years)
Pharmacokinetics of Vemurafenib: Area Under the Concentration-Time Curve (AUC)
AUC is a measure of the drug or biologic concentration in the body following administration.
Measured: Up to approximately 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2011 (estimated)
- Study startJun 2011
- Primary completionNov 2014
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01286753
- Sponsor's protocol ID
- NO25530
- Other IDs
- 2010-024133-23
- Status last verified
- Jul 2016
- First submitted
- 28 Jan 2011
- Last updated
- 7 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Brose MS, Cabanillas ME, Cohen EE, Wirth LJ, Riehl T, Yue H, Sherman SI, Sherman EJ. Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016 Sep;17(9):1272-82. doi: 10.1016/S1470-2045(16)30166-8. Epub 2016 Jul 23.
PubMed 27460442
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multi-Center Phase II Study of the BRAF Inhibitor Vemurafenib in Patients With Metastatic or Unresectable Papillary Thyroid Cancer (PTC) Positive for the BRAF V600 Mutation and Resistant to Radioactive Iodine
- ClinicalTrials.gov ID
- NCT01286753
- Acronym / sponsor ID
- NO25530
- Conditions
- Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- Jun 2011
- Primary completion
- Nov 2014 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 31 Jan 2011 (estimated)
- Results
- Posted 7 Sep 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This open-label, multi-center study will evaluate the safety and efficacy of Vemurafenib (RO5185426) in participants with metastatic or unresectable papillary thyroid cancer (PTC) positive for the BRAF V600 mutation and resistant to radioactive iodine therapy. Participants will receive vemurafenib 960 milligrams (mg) orally twice daily until progressive disease or unacceptable toxicity occurs.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tyrosine Kinase Inhibitor (TKI) Naive | Experimental | Drug: VemurafenibVemurafenib in participants naive to any prior systemic TKI therapy. |
| TKI Experienced | Experimental | Drug: VemurafenibVemurafenib in participants previously treated with TKI therapy active against vascular endothelial growth factor receptor 2 (VEGFR). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Adult participants. >/= 18 years of age
- Histologically confirmed metastatic or unresectable papillary thyroid cancer for which standard curative or palliative measures do not exist or are no longer effective; participants whose tumors exhibit areas of "other histology" may be enrolled, provided the tumor histology remains predominantly papillary
- Positive for BRAF V600 mutation (Roche Cobas 4800 BRAF V600 Mutation Test)
- Radioactive Iodine resistant disease
- Prior therapy excluding (Cohort 1, TKI Naive) or including (Cohort 2, TKI Experienced) TKI
Key exclusion criteria (8 listed)
- Histological diagnosis other than papillary PTC, including squamous cell variants of PTC or PTC with areas of squamous metaplasia
- Active or untreated central nervous system metastases
- History of or known carcinomatous meningitis
- Anticipated or ongoing administration of any anti-cancer therapies other than those administered in the study
- Active squamous cell skin cancer that has not been excised or adequately healed post excision
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 |
|---|---|---|
| VemurafenibAlso: Zelboraf®, RO5185426Vemurafenib 960 mg orally twice daily. | Drug | TKI Experienced, Tyrosine Kinase Inhibitor (TKI) Naive |
Primary outcome
Best Overall Response Rate in TKI-Naive Participants
Time frame: Up to approximately 4 years
Best overall response rate was assessed by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Best overall response rate: the percentage of participants with best objective response of complete response (CR) or partial response (PR) (calculated as the number of participants with best response CR or PR divided by the total number of efficacy-evaluable participants). CR: disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to < 10 millimeters (mm). PR: ≥ 30% decrease in the sum of diameters of target lesions, compared to the baseline sum diameters.
7 secondary outcomes
Best Overall Response Rate in TKI-Experienced Participants
Time frame: Up to approximately 4 years
Clinical Benefit Rate
Time frame: Up to approximately 4 years
Duration of Response
Time frame: From the date of first qualifying response to the date of PD or death for any cause (up to approximately 4 years)
Progression-Free Survival
Time frame: From the day of first treatment until the first documented PD or death (up to approximately 4 years)
Overall Survival
Time frame: From the date of first treatment to the date of death for any cause (up to approximately 4 years)
Percentage of Participants With Adverse Events
Time frame: Baseline until 28 days after the last dose of study treatment or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 4 years)
Pharmacokinetics of Vemurafenib: Area Under the Concentration-Time Curve (AUC)
Time frame: Up to approximately 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27460442Brose MS, Cabanillas ME, Cohen EE, Wirth LJ, Riehl T, Yue H, Sherman SI, Sherman EJ. Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016 Sep;17(9):1272-82. doi: 10.1016/S1470-2045(16)30166-8. Epub 2016 Jul 23.
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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.
Clinical Trials study director
Hoffmann-La Roche
16 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vemurafenib in people with Neoplasms, run by Hoffmann-La Roche at 16 sites in 4 countries.
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 8 inclusion and 8 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 7 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, France, Italy, Netherlands. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 7 Sep 2016). 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?
Best Overall Response Rate in TKI-Naive Participants (time frame: Up to approximately 4 years). 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 NCT01286753, 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 7 Sep 2016.