Trial Outcomes & Findings for CUDC-907 Treatment in People With Metastatic and Locally Advanced Thyroid Cancer (NCT NCT03002623)

Last Updated: 2018-12-21

Results Overview

Clinical response, defined as a complete response + partial response (CR+PR) to CUDC-907 treatment, was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response is at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

7 participants

Primary outcome timeframe

Approximately 6 months

Results posted on

2018-12-21

Participant Flow

Participant milestones

Participant milestones
Measure	Anaplastic Thyroid Cancer CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.	Poorly Differentiated/Variants of Thyroid Cancer CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer. CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.
Overall Study STARTED	4	3
Overall Study COMPLETED	2	2
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Anaplastic Thyroid Cancer CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.	Poorly Differentiated/Variants of Thyroid Cancer CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer. CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.
Overall Study Lost to Follow-up	1	0
Overall Study Physician Decision	1	1

Baseline Characteristics

CUDC-907 Treatment in People With Metastatic and Locally Advanced Thyroid Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Anaplastic Thyroid Cancer n=4 Participants CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.	Poorly Differentiated/Variants of Thyroid Cancer n=3 Participants CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer. CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.	Total n=7 Participants Total of all reporting groups
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Age, Continuous	59.5 years STANDARD_DEVIATION 19.18 • n=5 Participants	66.6 years STANDARD_DEVIATION 1.39 • n=7 Participants	62.5 years STANDARD_DEVIATION 16.15 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Mexican, Puerto Rican, Cuban, Central/So American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Not meeting definition for Hispanic or Latino	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment United States	4 participants n=5 Participants	3 participants n=7 Participants	7 participants n=5 Participants

PRIMARY outcome

Timeframe: Approximately 6 months

Outcome measures

Outcome measures
Measure	Anaplastic Thyroid Cancer n=4 Participants CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.	Poorly Differentiated/Variants of Thyroid Cancer n=3 Participants CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer. CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.
Number of Participants With a Clinical Response (Complete Response (CR) + Partial Response (PR)) Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Complete Response	0 Participants	0 Participants
Number of Participants With a Clinical Response (Complete Response (CR) + Partial Response (PR)) Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Partial Response	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Approximately 6 months

Population: One participant was non-evaluable (withdrew consent).

Time in days from initiation of treatment until tumor grows more than 20%. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Anaplastic Thyroid Cancer n=3 Participants CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.	Poorly Differentiated/Variants of Thyroid Cancer n=2 Participants CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer. CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.
Median Amount of Time Subject Survives Without Disease Progression After Treatment	31.3 Days Interval 21.0 to 45.0	147 Days Interval 127.0 to 167.0

SECONDARY outcome

Timeframe: Approximately 12 months

Population: Participants are grouped together because of a small sample size and not enough power to compare the difference between two groups. No statistical analysis to be done.

Time in days from the initiation of treatment until death estimated by the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Anaplastic Thyroid Cancer n=6 Participants CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.	Poorly Differentiated/Variants of Thyroid Cancer CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer. CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.
Median Amount of Time Subject Survives After Therapy	127 Days Interval 66.5 to 187.5	—

SECONDARY outcome

Timeframe: At disease progression

Population: This outcome measure was not done. Data was collected but the correlation between mutation status of tumor and progression-free survival was not performed because of only BRAF V600E and the loss of tumor protein 53 (TP53) heterozygosity were found on a single patient each. Since only 1 mutant was found for each, no analysis was done.

The amount of time subject survives without disease progression is compared by patient tumor mutation status.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At disease progression

Population: This outcome measure was not done. Data was collected but no samples were analyzed because the experiment was not technically successful due to inconclusive results from immunohistochemistry (study of protein levels in tumor tissue) analysis of P13K/AKT and EGFR/RAS/RAF/MEK/ERK proteins.

The amount of time subject survives without disease progression is compared by the protein levels of PI3K/AKT and epidermal growth factor receptor (EGFR)/rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/methyl ethyl ketone (MEK)/extracellular-signal regulated kinase (ERK) in tumor tissue.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At disease progression

Population: This outcome measure was not done. Data was collected but not analyzed because the assessment of HDAC2 and survivin proteins cannot be reliably performed with consistent results.

The amount of time subject survives without disease progression is compared by the protein levels of HDAC2 and surviving in tumor tissue. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Date treatment consent signed to date off study, approximately 12 months and 13 days

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Anaplastic Thyroid Cancer n=4 Participants CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.	Poorly Differentiated/Variants of Thyroid Cancer n=3 Participants CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer. CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.
Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)	4 Participants	3 Participants

Adverse Events

Anaplastic Thyroid Cancer

Serious events: 2 serious events

Other events: 4 other events

Deaths: 2 deaths

Poorly Differentiated/Variants of Thyroid Cancer

Serious events: 1 serious events

Other events: 3 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Anaplastic Thyroid Cancer n=4 participants at risk CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.	Poorly Differentiated/Variants of Thyroid Cancer n=3 participants at risk CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer. CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.
General disorders Death	50.0% 2/4 • Number of events 2 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 13 days.

Other adverse events

Additional Information

Dr. Naris Nilubol

National Cancer Institute

Phone: 301- 451-2355

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Anaplastic Thyroid Cancer n=4 participants at risk CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.	Poorly Differentiated/Variants of Thyroid Cancer n=3 participants at risk CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer. CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.
Gastrointestinal disorders Abdominal pain	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
Investigations Alkaline phosphatase increased	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
Blood and lymphatic system disorders Anemia	0.00% 0/4 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	66.7% 2/3 • Number of events 4 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
Gastrointestinal disorders Constipation	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
Gastrointestinal disorders Diarrhea	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	66.7% 2/3 • Number of events 3 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
Nervous system disorders Dizziness	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/4 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	33.3% 1/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
General disorders Fatigue	100.0% 4/4 • Number of events 5 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/4 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
Investigations Lymphocyte count decreased	0.00% 0/4 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	66.7% 2/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	25.0% 1/4 • Number of events 2 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
Gastrointestinal disorders Nausea	25.0% 1/4 • Number of events 2 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
Investigations Neutrophil count decreased	0.00% 0/4 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
Musculoskeletal and connective tissue disorders Non-cardiac chest pain	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
Gastrointestinal disorders Pain	0.00% 0/4 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
Renal and urinary disorders Proteinuria	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
Vascular disorders Thromboembolic event	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
Gastrointestinal disorders Vomiting	25.0% 1/4 • Number of events 3 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	0.00% 0/3 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
Investigations Weight loss	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 13 days.
Investigations White blood cell decreased	0.00% 0/4 • Date treatment consent signed to date off study, approximately 12 months and 13 days.	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 13 days.