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

NCT03002623 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 17002917-C-0029
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The thyroid is a gland at the base of the throat. Thyroid cancer is a disease that people get when abnormal cells begin to grow in this gland. Researchers believe a new drug called CUDC-907 may be able to help people with thyroid cancer that has spread or has gotten worse. Objective: To see if CUDC-907 will shrink tumors in people with advanced thyroid cancer. Eligibility: People at least 18 years old who have been diagnosed with locally advanced and metastatic thyroid cancer. Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Electrocardiogram (ECG) heart test. Review of their symptoms and how they perform normal activities A scan will be performed. Some will have a computed tomographic scan (CT) that takes pictures of the body using a small amount of radiation. Some will have magnetic resonance imaging (MRI) that uses a magnetic field to take pictures. Bone scan (some participants) Fludeoxyglucose (FDG) positron emission tomography (PET) scan to produce a tumor image. A sample of their tumor from a previous surgery. They may have a biopsy of their tumor if a tumor sample is not available from a previous surgery. Participants will be given CUDC-907 in tablet form. They will take it by mouth once a day for 5 days, then take 2 days off, each week. While taking the study drug, participants will have study visits that repeat the screening tests. After they stop treatment, participants will have 3 follow-up visits over a year. They will repeat some tests. Then participants will be contacted by phone or e-mail every 6 months....

Conditions

Thyroid Neoplasms; Poorly Differentiated and Undifferentiated Thyroid Cancer; Differentiated Thyroid Cancer

Keywords

Dual Inhibitor of HDAC and P13K Signaling; HDAC2; EGFR/RAS/RAF/MEK/ERK Signaling Pathway Inhibition

Outcome Measures

Primary Outcomes (1)

• 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

  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.

  Approximately 6 months

Secondary Outcomes (6)

• Median Amount of Time Subject Survives Without Disease Progression After Treatment

  Approximately 6 months

• Median Amount of Time Subject Survives After Therapy

  Approximately 12 months

• Correlation Between Mutation Status of Tumor and Median Amount of Time Subject Survives Without Disease Progression After Treatment

  At disease progression

• Correlation Between Activation of the Phosphoinositide 3-kinase (PI3K)/Protein Kinase B (AKT) and EGFR/RAS/RAF/MEK/ERK Pathways in Tumor Tissue and Median Amount of Time Subject Survives Without Disease Progression After Treatment

  At disease progression

• Correlation Between Histone Deacetylase 2 (HDAC2) and Survivin Protein Levels in Tumor Tissue With Median Amount of Time Subject Survives Without Disease Progression After Treatment

  At disease progression

Study Arms (1)

Group

EXPERIMENTAL

CUDC-907 for thyroid cancer

Drug: CUDC-907

Interventions

CUDC-907 DRUG

60 mg (2 capsules of 30 mg capsules) will be given orally once a day 5 days on and 2 days off.

Group

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects greater than or equal to 18 years of age.
• Thyroid cancer histology or cytology that is aggressive (anaplastic/undifferentiated thyroid cancer, poorly differentiated thyroid cancer, Hurthle cell carcinoma, tall-cell variant of papillary thyroid cancer, sclerosing variant of papillary thyroid cancer).
• Measurable disease.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Absolute neutrophil count greater than or equal to 1,000/microL
• Platelets greater than or equal to 75,000/microL
• Creatinine less than or equal to 1.5 times upper limit of normal (ULN) or creatinine clearance \> 60ml for patients with creatinine levels 1.5 times above institutional ULN (calculated based on age, weight and sex
• Total bilirubin less than or equal to 1.5 times ULN; aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than or equal to 2.5 times ULN. For subjects with documented liver metastases, the AST/ALT may be less than or equal to 5 times ULN.
• Recovery to Grade 1 or baseline of any toxicity due to prior anticancer therapies (excluding alopecia).
• Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days prior to screening complete blood count (CBC) or Cycle 1, Day 1 treatment.
• Women of child bearing potential must have a negative serum pregnancy test.
• The effects of CUDC-907 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 30 days following the last study treatment.
• Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Able to provide written informed consent and to follow protocol requirements.

You may not qualify if:

• Systemic anticancer therapy within 4 weeks of study entry, except for subjects with anaplastic/undifferentiated thyroid cancer who may be enrolled immediately after discontinuation of previous therapy.
• Other investigational agents within 4 weeks prior to study treatment except for subjects with anaplastic/undifferentiated thyroid cancer who may be enrolled immediately of discontinuation of previous therapy.
• Pregnant women are excluded from this study because the potential risk of teratogenic or abortifacient effects of CUDC-907 is unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CUDC-907, breastfeeding should be discontinued if the mother is treated with CUDC-907. These potential risks may also apply to other agents used in this study.
• Diabetes mellitus that is not controlled with medication.
• Serious infection requiring intravenous antibiotic therapy within 14 days prior to study treatment.
• Evidence of central nervous system metastasis.
• Uncontrolled or severe cardiovascular disease, including myocardial infarction, unstable angina, or atrial fibrillation (AFib) within 6 months prior to study treatment, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, cardiac amyloidosis, or corrected QT interval (QTc) with Fridericia's (QTcF) correction that is unmeasurable or greater than or equal to 480 msec on screening electrocardiogram (ECG). (Note: for QTcF greater than or equal to 480 sec on the screening ECG, the ECG may be repeated twice at least 24 hours apart; the mean QTcF from the three screening ECGs must be \< 480 msec in order to meet eligibility for trial participation).
• Gastrointestinal disease or disorder that could interfere with the swallowing, oral absorption, or tolerance of CUDC-907. This includes uncontrolled diarrhea (\> 1 watery stool/day), major abdominal surgery, significant bowel obstruction and/or gastrointestinal diseases that could alter the assessment of pharmacokinetics or safety, including but not limited to: irritable bowel syndrome, ulcerative colitis, Crohn's disease and hemorrhagic coloproctitis.
• Unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a subject and/or compliance with the protocol.
• Second primary malignancy within 2 years of study entry other than adequately treated non-melanoma skin or superficial bladder cancer, curatively treated carcinoma in situ of the cervix or other curatively treated solid tumor deemed by the investigator to be at low risk for recurrence.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Simon D, Koehrle J, Reiners C, Boerner AR, Schmutzler C, Mainz K, Goretzki PE, Roeher HD. Redifferentiation therapy with retinoids: therapeutic option for advanced follicular and papillary thyroid carcinoma. World J Surg. 1998 Jun;22(6):569-74. doi: 10.1007/s002689900436.

  PMID: 9597930 BACKGROUND

• Nilubol N, Kebebew E. Should small papillary thyroid cancer be observed? A population-based study. Cancer. 2015 Apr 1;121(7):1017-24. doi: 10.1002/cncr.29123. Epub 2014 Nov 25.

  PMID: 25425528 BACKGROUND

• Kebebew E, Greenspan FS, Clark OH, Woeber KA, McMillan A. Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors. Cancer. 2005 Apr 1;103(7):1330-5. doi: 10.1002/cncr.20936.

  PMID: 15739211 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Thyroid Neoplasms; Thyroid Carcinoma, Anaplastic

Interventions

CUDC-907

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Dr. Naris Nilubol
• Organization: National Cancer Institute

niluboln@nih.gov

301- 451-2355

Study Officials

• Naris Nilubol, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a single group assignment. All patients regardless of subtype of thyroid cancer received one single treatment and follow up plan with option to continue the treatment when scan was negative.

Study Record Dates

• First Submitted: December 22, 2016
• First Posted: December 26, 2016
• Study Start: December 22, 2016
• Primary Completion: February 12, 2018
• Study Completion: February 12, 2018
• Last Updated: December 21, 2018
• Results First Posted: December 21, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)