Trial Outcomes & Findings for Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436 (NCT NCT01534897)

Last Updated: 2017-03-15

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

10 participants

Primary outcome timeframe

25 days after start of Dabrafenib (GSK2118436)

Results posted on

2017-03-15

Participant Flow

Recruitment period: July 2012-July 2013 Location: Massachusetts General Hospital Cancer Center Medical Clinic Number of patients recruited: 10 Recruitment goal: 10

All patients recruited were enrolled, and all patients completed the study.

Participant milestones

Participant milestones
Measure	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)
Overall Study STARTED	10
Overall Study Day 25 Iodine-131 Scan	10
Overall Study Day 37 Iodine-131 Treatment	6
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GSK2118436 n=10 Participants 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.
Age, Customized <=18 years	0 participants n=5 Participants
Age, Customized Between 18 and 65 years	4 participants n=5 Participants
Age, Customized >=65 years	6 participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants
Type of tumor Classic papillary	5 Participants n=5 Participants
Type of tumor Tall cell papillary	4 Participants n=5 Participants
Type of tumor Clear cell papillary	1 Participants n=5 Participants
Prior radioiodine treatments per patient	2 treatments n=5 Participants
Prior surgeries per patient (not including initial thyroidectomy)	3 surgeries n=5 Participants
Prior external-beam radiotherapy	3 participants n=5 Participants
Prior chemotherapy	0 participants n=5 Participants
Prior targeted therapy	0 participants n=5 Participants

PRIMARY outcome

Timeframe: 25 days after start of Dabrafenib (GSK2118436)

Outcome measures

Outcome measures
Measure	GSK2118436 n=10 Participants 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.
Increased Radioiodine Uptake	6 Participants

SECONDARY outcome

Timeframe: 2 years

Population: All patients completed dabrafenib without dose modification.

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).

Outcome measures

Outcome measures
Measure	GSK2118436 n=10 Participants 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.
Safety Analysis as Number of Participants With Adverse Events Experienced an Adverse Event	10 Participants
Safety Analysis as Number of Participants With Adverse Events Experienced a Serious Adverse Event	0 Participants
Safety Analysis as Number of Participants With Adverse Events Experienced a Grade 3, 4, or 5 Adverse Event	0 Participants

SECONDARY outcome

Timeframe: 2 years

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).

Outcome measures

Outcome measures
Measure	GSK2118436 n=10 Participants 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.
Clinical Benefit as Measured by Change in Tumor Size Stable Disease by RECIST	7 Participants
Clinical Benefit as Measured by Change in Tumor Size Progressive Disease by RECIST	1 Participants
Clinical Benefit as Measured by Change in Tumor Size Partial Response by RECIST	2 Participants

SECONDARY outcome

Timeframe: 2 years

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).

Outcome measures

Outcome measures
Measure	GSK2118436 n=10 Participants 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.
Number of Participants Who Complete the Study With Minimal Delays and no Dose Reductions	10 Participants

SECONDARY outcome

Timeframe: 3 months after radioiodine therapy

To evaluate clinical benefit as measured by change in serum tumor marker, thyroglobulin. Rising thyroglobulin is generally indicative of tumor growth.

Outcome measures

Outcome measures
Measure	GSK2118436 n=10 Participants 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.
Clinical Benefit as Measured by Change in Thyroglobulin Level decrease in serum thyroglobulin	4 Participants
Clinical Benefit as Measured by Change in Thyroglobulin Level increase in serum thryoglobulin	6 Participants

Adverse Events

GSK2118436

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	GSK2118436 n=10 participants at risk 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)
Skin and subcutaneous tissue disorders Skin Changes	80.0% 8/10 • Number of events 15 • 2 years
General disorders Fatigue	50.0% 5/10 • Number of events 5 • 2 years
Metabolism and nutrition disorders Hypocalcemia	20.0% 2/10 • Number of events 2 • 2 years
Gastrointestinal disorders Gastrointestinal	50.0% 5/10 • Number of events 8 • 2 years
Skin and subcutaneous tissue disorders Palmar-Plantar Erythrodysethesias	40.0% 4/10 • Number of events 4 • 2 years
General disorders Headache	30.0% 3/10 • Number of events 3 • 2 years
Blood and lymphatic system disorders Epistaxis	20.0% 2/10 • Number of events 2 • 2 years
Metabolism and nutrition disorders Creatinine Increase	20.0% 2/10 • Number of events 2 • 2 years
Metabolism and nutrition disorders Hypophosphatemia	10.0% 1/10 • Number of events 1 • 2 years
Metabolism and nutrition disorders Hyperglycemia	10.0% 1/10 • Number of events 1 • 2 years
Metabolism and nutrition disorders Hyponatremia	10.0% 1/10 • Number of events 1 • 2 years
Gastrointestinal disorders Nausea	20.0% 2/10 • Number of events 2 • 2 years
Metabolism and nutrition disorders Weight loss	20.0% 2/10 • Number of events 2 • 2 years

Additional Information

Dr. Lori J. Wirth

Massachusetts General Hospital Cancer Center

Phone: 617 724 4000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place