Clinical Trials Logo

Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT03838692
Other study ID # AAAR5196
Secondary ID
Status Withdrawn
Phase Phase 2
First received
Last updated
Start date July 26, 2019
Est. completion date June 14, 2021

Study information

Verified date October 2021
Source Columbia University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The primary objective of this study is to determine in an exploratory manner the objective overall response rate to ponatinib in the treatment of patients with advanced or metastatic MTC previously treated with cabozantinib or vandetanib who have tumors with rearranged-during-transfection (RET) mutations and have tumors without RET mutations.


Description:

Ponatinib is an investigational agent that blocks abnormal cancer proteins and therefore harms cancer cells. It was recently approved by the Food and Drug Administration for leukemia treatment, but is not approved for medullary thyroid cancer treatment. Early studies, however, have shown that medullary thyroid tumors respond to ponatinib. These studies were done in the laboratory and not performed on humans. This is a study designed for patients with medullary thyroid cancer. Treatment will consist of a drug called ponatinib which is a pill that taken once each day and continue throughout the duration of the study. The purpose of the study is to: 1. Determine if this treatment will be effective in decreasing the amount of cancer and, if it does, to determine how long the response will last. 2. Determine the side effects that may occur with this treatment. 3. To analyze genetic mutations in tumors to help us understand how tumors grow and how these drugs interact with the mechanisms within the tumor. Ponatinib has been given to many patients with leukemia and is now approved by the United States Food and Drug Administration for treatment of certain types of leukemia. This study will seek to determine if ponatinib can bring benefit to patients with medullary thyroid cancer.


Recruitment information / eligibility

Status Withdrawn
Enrollment 0
Est. completion date June 14, 2021
Est. primary completion date June 14, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Diagnosis of localized or metastatic unresectable MTC. - Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as =20 mm with conventional techniques or as =10 mm with spiral computerized tomography (CT) scan. - The last dose of previous therapy targeting RET kinase must be given at least 4 weeks - Previous treatment with cytotoxic chemotherapy, immunotherapy, or radiotherapy are permitted, if the last dose was given at least 4 weeks prior to the first dose of ponatinib - Patient must have failed (progressed on or been intolerant of) prior treatment with cabozantinib or vandetanib. - Age =18 years old - Eastern Cooperative Oncology Group (ECOG) performance status =2 - Normal organ and marrow function as defined below: - Negative pregnancy test for women of childbearing potential or male patients, even if surgically sterilized (i.e., status post-vasectomy), who: - Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or - Agree to completely abstain from heterosexual intercourse - Normal QT interval corrected on screening electrocardiogram (ECG) evaluation, defined as the corrected QT interval by Fredericia (QTcF) of =450 ms. - Ability to understand and the willingness to sign a written informed consent document and follow the guidelines of the clinical protocol including visits for treatment and follow up - Life expectancy of greater than 12 weeks - Available archival tissue or willingness to undergo fresh biopsy if no archival tissue is available. Exclusion Criteria: - Patients who are receiving any other investigational agent. - Patients with brain metastases or spinal cord compression unless they completed radiation therapy =4 weeks prior to the first dose of ponatinib and are stable without steroids or anti-convulsant therapy for =10 days. - Patients who cannot discontinue medications that are known to be associated with Torsades de Pointes. These medications are listed in Attachment 3 - Uncontrolled hypertension (systolic blood pressure >150 or diastolic blood pressure >100 - Significant or active cardiovascular disease within 6 months prior to enrollment - A history of pancreatitis or alcohol abuse - Uncontrolled hypertriglyceridemia (>450 mg/dL) - Major surgery (with the exception of minor surgical procedures, such as catheter placement or tumor biopsy) within 28 days prior to the first dose of ponatinib - Ongoing or active infection including known history of human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C (HCV). Testing for these viruses is not required in the absence of a history of infection. - Suffer from any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of the safety of the study drug - Evidence of a bleeding diathesis that cannot be corrected with standard therapy or factor replacement - Presence of another primary malignancy within the past 2 years (except for non-melanoma skin cancer or cervical cancer in situ. Prior prostate cancer is also permitted if prostate-specific antigen (PSA) is now undetectable) - Pregnant or lactating - History of allergic reactions attributed to compounds of similar chemical or biologic composition to investigational agent

Study Design


Intervention

Drug:
Ponatinib
A daily oral dose at 30 mg.

Locations

Country Name City State
n/a

Sponsors (2)

Lead Sponsor Collaborator
Antonio Fojo Millennium Pharmaceuticals, Inc.

Outcome

Type Measure Description Time frame Safety issue
Other Total Number of Adverse Reactions Testing safety and toxicity assessed using CTCAE criteria 24 months
Primary Objective Response Rate (ORR) ORR is defined as the proportion of the subjects in the analysis population who have a complete response (CR) or partial response (PR). Responses are based on assessments per RECIST. 24 months
Secondary Progression-Free Survival (PFS) PFS is defined as the time from the first day of trial treatment to the first documented disease progression per the Kaplan-Meier curve. 24 months
See also
  Status Clinical Trial Phase
Active, not recruiting NCT03643055 - 18F-Fluorocholine PET/CT in Medullary Thyroid Cancer
Terminated NCT02709889 - Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid Tumors Phase 1/Phase 2
Recruiting NCT06277180 - 68Ga-TCR-FAPI PET/CT Guided Precision Surgery for MTC N/A
Withdrawn NCT04760288 - A Study of Pralsetinib Versus Standard of Care (SOC) for Treatment of RET-Mutated Medullary Thyroid Cancer (MTC). Phase 3
Not yet recruiting NCT06079723 - A Detailed Look At What Patients Experience In Medullary Thyroid Cancer Clinical Study
Recruiting NCT01739634 - The Efficacy of CASAD in Patients With Diarrhea Related to Medullary Thyroid Cancer Phase 1/Phase 2
Recruiting NCT03157128 - A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001) Phase 1/Phase 2
Completed NCT02856347 - Prospective Study Evaluating the Medullary Thyroid Cancer Management's Care Using PET F-DOPA in Patients With a High Level of Postoperative Residual Thyrocalcitonin N/A
Completed NCT03037385 - Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors Phase 1/Phase 2
Active, not recruiting NCT04280081 - A Study of Selpercatinib (LY3527723) in Participants With Advanced Solid Tumors Including RET Fusion-positive Solid Tumors, Medullary Thyroid Cancer and Other Tumors With RET Activation Phase 2
Not yet recruiting NCT06292988 - Predictive Factors for Medullary Thyroid Cancer Aggressiveness
Completed NCT01757470 - Vandetanib Risk Minimisation Effectiveness N/A
Recruiting NCT05830500 - Study of Anlotinib in Patients With Advanced Medullary Thyroid Carcinoma Phase 4
Recruiting NCT03899792 - A Study of Oral LOXO-292 (Selpercatinib) in Pediatric Participants With Advanced Solid or Primary Central Nervous System (CNS) Tumors Phase 1/Phase 2
Recruiting NCT01660984 - Natural History Study of Children and Adults With Medullary Thyroid Cancer
Terminated NCT02363647 - Personalized Cancer Therapy for Patients With Metastatic Medullary Thyroid or Metastatic Colon Cancer N/A
Terminated NCT00582712 - An Initial Study of Lithium in Patients With Medullary Thyroid Cancer Phase 2
Recruiting NCT06141369 - Treatment of Advanced Endocrine Tumor With Iindividualized mRNA Neoantigen Vaccine (mRNA-0523-L001) N/A
Completed NCT06243965 - Is Desmoplastic Stromal Reaction Useful to Modulate Lymph Node Dissection in Sporadic Medullary Thyroid Carcinoma?
Active, not recruiting NCT01298323 - Study to Determine if Contacting Patients With MTC More Frequently Results in Earlier Detection and Treatment of Signs and Symptoms of AEs and Thus a Decrease in the Percentage of Time Patients Experience AEs During First 12 Months on Vandetanib Treatment Phase 3