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| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
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Radioactive iodine therapy is often part of the standard treatment for Papillary Thyroid Carcinoma (PTC) patients. However, in many patients, tumors develop a resistance or no longer respond to radioactive iodine therapy (iodine-refractory). Several lines of evidence suggest that blocking the BRAF gene may help to re-sensitize the tumors to radioactive iodine. BRAF is a protein that plays a central role in the growth and survival of cancer cells in some types of PTC. The investigational drug GSK2118436 may work by blocking the BRAF protein in cancer cells lines and tumors that have a mutated BRAF gene.
In this research study, the investigators are looking to see if GSK2118436 can re-sensitize iodine-refractory PTC to radioactive iodine therapy. The investigators are also looking at the safety of adding GSK2118436 to radioactive iodine therapy.
You will take GSK2118436 capsules by mouth for 28 straight days. If your Day 28 whole body radioactive iodine scan demonstrates significant uptake of iodine, you will take GSK2118436 for an additional 14 days (Days 29-42). You will be given a drug diary to record when you take GSK2118436. This diary will also contain instructions on how to take GSK2118436.
Prior to Day 1
Day 2:
Days 21 and 22: The drug thyrogen will be administered as in injection into your buttocks on Days 21 and 22 in preparation for your whole body radioactive iodine scan on Day 28. Thyrogen is used as a diagnostic tool to help determine the status of your cancer and is approved for use in thyroid cancer patients.
Day 23: To prepare for the whole body radioactive iodine scan, you will be asked to swallow a capsule of radioactive iodine which will be absorbed by any remaining thyroid cells in your body. Radioactive iodine is approved for use in thyroid cancer patients. You will then be asked to return for the scan on Day 28.You will be asked to sign a separate consent for the radioactive iodine.
Days 1-28:
If your Day 28 whole body radioactive iodine scan demonstrates significant uptake of iodine, you will have the following tests done within 24 hours:
If your Day 28 whole body radioactive iodine scan demonstrates significant uptake of iodine, you will continue treatment with GSK2118436 and have the following study visits:
Days 35 and 36: The drug thyrogen will be administered as in injection into your buttocks on Days 35 and 36 in preparation for your whole body radioactive iodine scan on Day 42.
Day 37: You will be given a therapeutic dose of radioactive iodine. You will be given a separate consent form to sign for your radioactive iodine treatment. You will then be asked to return for the whole body radioactive iodine scan on Day 42.
Day 39:
Day 42:
After the final dose of the study drug: All participants will have a follow up visit 3 months after you stop the study drug. You will have the following tests at this visit:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GSK2118436 | Experimental | Intervention: GSK2118436 (dabrafenib) 150mg by mouth twice per day for 28 days, continued to day 42 if the Day 25 Iodine-131 scan shows new uptake. Patients with new Iodine-131 uptake on Day 25 who continue dabrafenib to day 42 receive a treatment dose (150 mCi) of Iodine-131 on Day 37. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2118436 | Drug | 150mg twice per day orally for 28 days (42 days if Iodine-131 scan on Day 25 shows new uptake) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Increased Radioiodine Uptake | Number of patients with radioiodine-refractory metastatic BRAF V600E-mutant PTC who have increased radioiodine uptake in their disease sites while on dabrafenib. Radioiodine uptake is assessed by whole body scan and areas of interest are identified by nuclear medicine physicians. | 25 days after start of Dabrafenib (GSK2118436) |
| Measure | Description | Time Frame |
|---|---|---|
| Safety Analysis as Number of Participants With Adverse Events | To evaluate the safety and tolerability, as determined by adverse event and serious adverse event reporting, of GSK2118436 in combination with whole body iodine scans (all patients) and treatment doses of radioactive iodine (patients whose tumors demonstrate significant iodine uptake). | 2 years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stephen M Rothenberg, MD, PhD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02215 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25549723 | Result | Rothenberg SM, McFadden DG, Palmer EL, Daniels GH, Wirth LJ. Redifferentiation of iodine-refractory BRAF V600E-mutant metastatic papillary thyroid cancer with dabrafenib. Clin Cancer Res. 2015 Mar 1;21(5):1028-35. doi: 10.1158/1078-0432.CCR-14-2915. Epub 2014 Dec 30. |
| Label | URL |
|---|---|
| pubmed url for article | View source |
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All patients recruited were enrolled, and all patients completed the study.
Recruitment period: July 2012-July 2013 Location: Massachusetts General Hospital Cancer Center Medical Clinic Number of patients recruited: 10 Recruitment goal: 10
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| ID | Title | Description |
|---|---|---|
| FG000 | GSK2118436 | Note: This is a single arm feasibility study. Intervention: GSK2118436 (dabrafenib) 150mg by mouth twice per day for 28 days, continued to day 42 if the Day 25 Iodine-131 scan shows new uptake. Patients with new Iodine-131 uptake on Day 25 who continue dabrafenib to day 42 receive a treatment dose (150 mCi) of Iodine-131 on Day 37. GSK2118436: 150mg twice per day orally for 28 days (42 days if Iodine-131 scan on Day 25 shows new uptake) |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | GSK2118436 | Intervention: GSK2118436 (dabrafenib) 150mg by mouth twice per day for 28 days, continued to day 42 if the Day 25 Iodine-131 scan shows new uptake. Patients with new Iodine-131 uptake on Day 25 who continue dabrafenib to day 42 receive a treatment dose (150 mCi) of Iodine-131 on Day 37. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Increased Radioiodine Uptake | Number of patients with radioiodine-refractory metastatic BRAF V600E-mutant PTC who have increased radioiodine uptake in their disease sites while on dabrafenib. Radioiodine uptake is assessed by whole body scan and areas of interest are identified by nuclear medicine physicians. | Posted | Count of Participants | Participants | 25 days after start of Dabrafenib (GSK2118436) |
|
2 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | GSK2118436 | Intervention: GSK2118436 (dabrafenib) 150mg by mouth twice per day for 28 days, continued to day 42 if the Day 25 Iodine-131 scan shows new uptake. Patients with new Iodine-131 uptake on Day 25 who continue dabrafenib to day 42 receive a treatment dose (150 mCi) of Iodine-131 on Day 37. GSK2118436: 150mg twice per day orally for 28 days (42 days if Iodine-131 scan on Day 25 shows new uptake) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Skin Changes | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Lori J. Wirth | Massachusetts General Hospital Cancer Center | 617 724 4000 | lwirth@mgh.harvard.edu |
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| ID | Term |
|---|---|
| D000077273 | Thyroid Cancer, Papillary |
| D013964 | Thyroid Neoplasms |
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D000231 | Adenocarcinoma, Papillary |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
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| ID | Term |
|---|---|
| C561627 | dabrafenib |
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| Clinical Benefit as Measured by Change in Tumor Size | To evaluate clinical benefit as measured by objective response rate per modified RECIST 1.1, which assesses changes in size of measurable tumors. (per RECIST, a partial response (PR) = at least 30% decrease in size of tumor; progressive disease (PD) = at least 20% increase in size of tumor; stable disease (SD) = neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD). | 2 years |
| Number of Participants Who Complete the Study With Minimal Delays and no Dose Reductions | To determine the feasibility of: (a) administering GSK2118436 for 28 days in patients with BRAF V600E-mutant PTC, prior to whole body iodine scanning (all patients); and (b) administering GSK2118436 for an additional 14 days, prior to administering treatment doses of radioactive iodine (patients whose tumors demonstrate significant iodine uptake after 28 days of treatment). | 2 years |
| Clinical Benefit as Measured by Change in Thyroglobulin Level | To evaluate clinical benefit as measured by change in serum tumor marker, thyroglobulin. Rising thyroglobulin is generally indicative of tumor growth. | 3 months after radioiodine therapy |
| participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Type of tumor | Count of Participants | Participants |
|
| Prior radioiodine treatments per patient | Median | Full Range | treatments |
|
| Prior surgeries per patient (not including initial thyroidectomy) | Median | Full Range | surgeries |
|
| Prior external-beam radiotherapy | Number | participants |
|
| Prior chemotherapy | Number | participants |
|
| Prior targeted therapy | Number | participants |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Secondary | Safety Analysis as Number of Participants With Adverse Events | To evaluate the safety and tolerability, as determined by adverse event and serious adverse event reporting, of GSK2118436 in combination with whole body iodine scans (all patients) and treatment doses of radioactive iodine (patients whose tumors demonstrate significant iodine uptake). | All patients completed dabrafenib without dose modification. | Posted | Count of Participants | Participants | 2 years |
|
|
|
| Secondary | Clinical Benefit as Measured by Change in Tumor Size | To evaluate clinical benefit as measured by objective response rate per modified RECIST 1.1, which assesses changes in size of measurable tumors. (per RECIST, a partial response (PR) = at least 30% decrease in size of tumor; progressive disease (PD) = at least 20% increase in size of tumor; stable disease (SD) = neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD). | Posted | Count of Participants | Participants | 2 years |
|
|
|
| Secondary | Number of Participants Who Complete the Study With Minimal Delays and no Dose Reductions | To determine the feasibility of: (a) administering GSK2118436 for 28 days in patients with BRAF V600E-mutant PTC, prior to whole body iodine scanning (all patients); and (b) administering GSK2118436 for an additional 14 days, prior to administering treatment doses of radioactive iodine (patients whose tumors demonstrate significant iodine uptake after 28 days of treatment). | Posted | Count of Participants | Participants | 2 years |
|
|
|
| Secondary | Clinical Benefit as Measured by Change in Thyroglobulin Level | To evaluate clinical benefit as measured by change in serum tumor marker, thyroglobulin. Rising thyroglobulin is generally indicative of tumor growth. | Posted | Count of Participants | Participants | 3 months after radioiodine therapy |
|
|
|
| 0 |
| 10 |
| 10 |
| 10 |
| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Gastrointestinal | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Palmar-Plantar Erythrodysethesias | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Headache | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Epistaxis | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Creatinine Increase | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Weight loss | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
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| D009370 |
| Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D006258 | Head and Neck Neoplasms |
| D004700 | Endocrine System Diseases |
| D013959 | Thyroid Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |