Trial Outcomes & Findings for Reacquisition of Radioactive Iodine (RAI) Uptake of RAI-Refractory Metastatic Thyroid Cancers by Pretreatment With the Selective MEK Inhibitor AZD6244 (NCT NCT00970359)

NCT ID: NCT00970359

Last Updated: 2017-04-12

Results Overview

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 24 participants
• Primary outcome timeframe: 2 years
• Results posted on: 2017-04-12

Participant Flow

Participant milestones

Measure	AZD6244 AZD6244: Within 1 week of starting the study: Low iodine diet The patient will receive three bottles of capsules containing the drug AZD6244. Each capsule contains 25 milligrams of AZD6244. They will take 3 capsules orally, by mouth twice a day for 4 weeks. AZD6244 should be taken on an empty stomach (either one hour before or 2 hours after meals). AZD6244 capsules should be taken with water only. Lesional dosimetry with iodine-124 PET will be done twice, at the beginning and at the end of the study. This is done the same way that a radioactive iodine scan is done and is spread out over 5 days. It requires injection with human recombinant TSH (Thyrogen) on day 1 and 2, as well as blood tests on day 1 and day 5. On day 3, you will receive the iodine-124 in form of an oral drink, and the PET scan will be obtained on day 5. You will need to follow a low iodine diet starting 5 days before and throughout the process.
Overall Study STARTED	24
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Measure

AZD6244 AZD6244: Within 1 week of starting the study: Low iodine diet The patient will receive three bottles of capsules containing the drug AZD6244. Each capsule contains 25 milligrams of AZD6244. They will take 3 capsules orally, by mouth twice a day for 4 weeks. AZD6244 should be taken on an empty stomach (either one hour before or 2 hours after meals). AZD6244 capsules should be taken with water only. Lesional dosimetry with iodine-124 PET will be done twice, at the beginning and at the end of the study. This is done the same way that a radioactive iodine scan is done and is spread out over 5 days. It requires injection with human recombinant TSH (Thyrogen) on day 1 and 2, as well as blood tests on day 1 and day 5. On day 3, you will receive the iodine-124 in form of an oral drink, and the PET scan will be obtained on day 5. You will need to follow a low iodine diet starting 5 days before and throughout the process.

Overall Study Not Treated

4

Baseline Characteristics

Reacquisition of Radioactive Iodine (RAI) Uptake of RAI-Refractory Metastatic Thyroid Cancers by Pretreatment With the Selective MEK Inhibitor AZD6244

Baseline characteristics by cohort

Measure	AZD6244 n=24 Participants AZD6244: Within 1 week of starting the study: Low iodine diet The patient will receive three bottles of capsules containing the drug AZD6244. Each capsule contains 25 milligrams of AZD6244. They will take 3 capsules orally, by mouth twice a day for 4 weeks. AZD6244 should be taken on an empty stomach (either one hour before or 2 hours after meals). AZD6244 capsules should be taken with water only. Lesional dosimetry with iodine-124 PET will be done twice, at the beginning and at the end of the study. This is done the same way that a radioactive iodine scan is done and is spread out over 5 days. It requires injection with human recombinant TSH (Thyrogen) on day 1 and 2, as well as blood tests on day 1 and day 5. On day 3, you will receive the iodine-124 in form of an oral drink, and the PET scan will be obtained on day 5. You will need to follow a low iodine diet starting 5 days before and throughout the process.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	14 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Region of Enrollment United States	24 participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years

Outcome measures

Measure	AZD6244 n=20 Participants AZD6244: Within 1 week of starting the study: Low iodine diet The patient will receive three bottles of capsules containing the drug AZD6244. Each capsule contains 25 milligrams of AZD6244. They will take 3 capsules orally, by mouth twice a day for 4 weeks. AZD6244 should be taken on an empty stomach (either one hour before or 2 hours after meals). AZD6244 capsules should be taken with water only. Lesional dosimetry with iodine-124 PET will be done twice, at the beginning and at the end of the study. This is done the same way that a radioactive iodine scan is done and is spread out over 5 days. It requires injection with human recombinant TSH (Thyrogen) on day 1 and 2, as well as blood tests on day 1 and day 5. On day 3, you will receive the iodine-124 in form of an oral drink, and the PET scan will be obtained on day 5. You will need to follow a low iodine diet starting 5 days before and throughout the process.
Number of Patients Whose Tumor(s) Acquire an Increased Propensity for Iodine Uptake as Detected on Iodine-124 Positron Emission Tomography Scan New and/or increase	12 participants
Number of Patients Whose Tumor(s) Acquire an Increased Propensity for Iodine Uptake as Detected on Iodine-124 Positron Emission Tomography Scan Remained the same or less	8 participants

PRIMARY outcome

Timeframe: 6 months

Population: Only patients treated with radioiodine.

as defined by the RECIST v1.1 criteria Descriptive statistics will be used to summarize the data.

Outcome measures

Measure	AZD6244 n=8 Participants AZD6244: Within 1 week of starting the study: Low iodine diet The patient will receive three bottles of capsules containing the drug AZD6244. Each capsule contains 25 milligrams of AZD6244. They will take 3 capsules orally, by mouth twice a day for 4 weeks. AZD6244 should be taken on an empty stomach (either one hour before or 2 hours after meals). AZD6244 capsules should be taken with water only. Lesional dosimetry with iodine-124 PET will be done twice, at the beginning and at the end of the study. This is done the same way that a radioactive iodine scan is done and is spread out over 5 days. It requires injection with human recombinant TSH (Thyrogen) on day 1 and 2, as well as blood tests on day 1 and day 5. On day 3, you will receive the iodine-124 in form of an oral drink, and the PET scan will be obtained on day 5. You will need to follow a low iodine diet starting 5 days before and throughout the process.
Tumor Response Defined as Either a Complete Response or Partial Response Partial Response	5 participants
Tumor Response Defined as Either a Complete Response or Partial Response Stable Disease	3 participants

SECONDARY outcome

Timeframe: At 2 months and 6 months after Radioiodine administration

Population: Only patients treated with Radioiodine.

Will perform a Wilcoxon signed rank test for paired samples to compare the serum thyroglobulin level before and after 131I treatment in the subset of patients treated with 131I following AZD6244.

Outcome measures

Measure	AZD6244 n=8 Participants AZD6244: Within 1 week of starting the study: Low iodine diet The patient will receive three bottles of capsules containing the drug AZD6244. Each capsule contains 25 milligrams of AZD6244. They will take 3 capsules orally, by mouth twice a day for 4 weeks. AZD6244 should be taken on an empty stomach (either one hour before or 2 hours after meals). AZD6244 capsules should be taken with water only. Lesional dosimetry with iodine-124 PET will be done twice, at the beginning and at the end of the study. This is done the same way that a radioactive iodine scan is done and is spread out over 5 days. It requires injection with human recombinant TSH (Thyrogen) on day 1 and 2, as well as blood tests on day 1 and day 5. On day 3, you will receive the iodine-124 in form of an oral drink, and the PET scan will be obtained on day 5. You will need to follow a low iodine diet starting 5 days before and throughout the process.
Change From Baseline in Serum Thyroglobulin Levels After Treatment With 131I at 2 months	89 percentage of reduction of levels Interval 74.4 to 99.9
Change From Baseline in Serum Thyroglobulin Levels After Treatment With 131I at 6 months	80 percentage of reduction of levels Interval 5.1 to 100.0

Adverse Events

AZD6244

Serious events: 2 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Measure	AZD6244 n=24 participants at risk AZD6244: Within 1 week of starting the study: Low iodine diet The patient will receive three bottles of capsules containing the drug AZD6244. Each capsule contains 25 milligrams of AZD6244. They will take 3 capsules orally, by mouth twice a day for 4 weeks. AZD6244 should be taken on an empty stomach (either one hour before or 2 hours after meals). AZD6244 capsules should be taken with water only. Lesional dosimetry with iodine-124 PET will be done twice, at the beginning and at the end of the study. This is done the same way that a radioactive iodine scan is done and is spread out over 5 days. It requires injection with human recombinant TSH (Thyrogen) on day 1 and 2, as well as blood tests on day 1 and day 5. On day 3, you will receive the iodine-124 in form of an oral drink, and the PET scan will be obtained on day 5. You will need to follow a low iodine diet starting 5 days before and throughout the process.
Gastrointestinal disorders Gastric ulcer	4.2% 1/24 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	4.2% 1/24 • Number of events 1

Other adverse events

Measure	AZD6244 n=24 participants at risk AZD6244: Within 1 week of starting the study: Low iodine diet The patient will receive three bottles of capsules containing the drug AZD6244. Each capsule contains 25 milligrams of AZD6244. They will take 3 capsules orally, by mouth twice a day for 4 weeks. AZD6244 should be taken on an empty stomach (either one hour before or 2 hours after meals). AZD6244 capsules should be taken with water only. Lesional dosimetry with iodine-124 PET will be done twice, at the beginning and at the end of the study. This is done the same way that a radioactive iodine scan is done and is spread out over 5 days. It requires injection with human recombinant TSH (Thyrogen) on day 1 and 2, as well as blood tests on day 1 and day 5. On day 3, you will receive the iodine-124 in form of an oral drink, and the PET scan will be obtained on day 5. You will need to follow a low iodine diet starting 5 days before and throughout the process.
Investigations Blood bilirubin increased	4.2% 1/24 • Number of events 2
Investigations Creatinine increased	4.2% 1/24 • Number of events 2
Metabolism and nutrition disorders Hyperglycemia	8.3% 2/24 • Number of events 2
Metabolism and nutrition disorders Hyperkalemia	4.2% 1/24 • Number of events 1
Vascular disorders Hypertension	20.8% 5/24 • Number of events 6
Metabolism and nutrition disorders Hypocalcemia	8.3% 2/24 • Number of events 3
Musculoskeletal and connective tissue disorders Pain in extremity	4.2% 1/24 • Number of events 1
Cardiac disorders Palpitations	4.2% 1/24 • Number of events 1
Skin and subcutaneous tissue disorders Rash acneiform	12.5% 3/24 • Number of events 4
Skin and subcutaneous tissue disorders Rash maculo-papular	16.7% 4/24 • Number of events 4

Additional Information

Dr. Alan Ho

Memorial Sloan Kettering Cancer Center

Phone: 646-888-4235

Email: hoa@mskcc.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place