Trial record 1 of 1 for:
everolimus and ca4p
Fosbretabulin With Everolimus in Neuroendocrine Tumors With Progression
This study is currently recruiting participants.
Verified April 2017 by Lowell Anthony, MD, University of Kentucky
First Posted: January 9, 2017
Last Update Posted: April 24, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Know the risks and potential benefits of clinical studies and talk to your health care provider before participating.
Read our disclaimer for details.
Information provided by (Responsible Party):
Lowell Anthony, MD, University of Kentucky
This is a single center, open label, phase I study involving grade I-III gastroenteropancreatic neuroendocrine tumors, consisting of a dose escalation Part A followed by an expansion cohort Part B. On Part A Patients will be treated with daily oral everolimus. Fosbretabulin will be administered IV either q3 weekly or q weekly based on PO CRM cohort. Part B: Once the investigators have established an MTD in Part A, the investigators will be treating 15 more patients at that dose combination. The primary and secondary objectives of the expansion cohort will be similar to Part A of the study, i.e., to establish a safety profile of the experimental drug combination and to collect and assess efficacy data. Patients will be treated with concurrent everolimus and fosbretabulin for 12 weeks.
||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
||A Phase 1 Study of Fosbretabulin in Combination With Everolimus in Neuroendocrine Tumors (Grades 1-3) That Have Progressed After at Least One Prior Regimen for Metastatic Disease
Primary Outcome Measures:
Secondary Outcome Measures:
- Incidence of Toxicities [ Time Frame: 12 weeks ]
Incidence of patients reporting at least one adverse event per NCI CTCAE v4.0
- Anti-tumor activity [ Time Frame: 12 weeks ]
Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes.
| Estimated Enrollment:
| Actual Study Start Date:
||March 6, 2017
| Estimated Study Completion Date:
||December 31, 2018
| Estimated Primary Completion Date:
||August 31, 2018 (Final data collection date for primary outcome measure)
Experimental: everolimus + fosbretabulin
everolimus + fosbretabulin
A variety of treatment options are available for NETs with carcinoid syndrome including surgical and medical therapies. Most subjects require somatostatin analogs to control the symptoms of carcinoid syndrome. Subjects who no longer respond to somatostatin and other liver-directed therapies, who experience progression of disease and increasing symptoms have limited options, including participation in a clinical trial. Recently everolimus and sunitinib have been approved for the treatment of subjects with progressive locally advanced or metastatic neuroendocrine tumors. Based on the preclinical data in models of NETs and the clinical activity seen in NETS and other tumor types that have existing tumor vascculature, this study will examine the effectiveness of fosbretabulin given in combination with everolimus in subjects with GI-NETs and PNETs.The vasoconstrictive effect of fosbretabulin is potent, though short-lived (4-8 hours), with no cumulative adverse effect. Everolimus inhibits angiogenesis, slows tumor growth and has a prolonged half-life (30 hours). Combining these two agents with distinctly different mechanisms of action may improve tumor control without additional toxicities, and has the potential of reducing drug resistance.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:
||18 Years and older (Adult, Senior)
|Sexes Eligible for Study:
|Accepts Healthy Volunteers:
- Patients who have had prior everolimus but were not able to tolerate a 10 mg daily dose.
- Prior chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Child Pugh Class B or greater hepatic dysfunction.
- Patients who are receiving any other investigational agents.
- Patients with known brain metastases because of their poor prognosis and likelihood to develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to fosbretabulin
- Uncontrolled hypertension (HTN); sustained blood pressure (BP) greater than 150/100 mmHg
- Must not have had any unstable angina or myocardial infarction within 4 months prior to enrollment to treatment, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker.
- Must not have any evidence of other clinically active cancer and have no history of prior malignancy within the past 3 years with the exception of: a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less and with stable prostatespecific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival for the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal glands or pancreas.
- Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with everolimus and fosbretabulin. In addition, these patients are at increased risk of lethal infections when treated with marrowsuppressive therapy. Appropriate studies will be initiated for patients receiving combination antiretroviral therapy when indicated.
- History of prior cerebrovascular event, (including transient ischemic attack) within 6 months of start of screening.
- Current thrombotic or hemorrhagic disorder/event or history of prior event within 6 months of start of Screening
- Corrected QT interval ([QTc] Fridericia) > 480 ms
- Significant vascular disease or recent peripheral arterial thrombosis
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03014297
|University of Kentucky Markey Cancer Center
|Lexington, Kentucky, United States, 40502 |
|Contact: Aman Chauhan, MD 859-323-6522 firstname.lastname@example.org |
|Contact: Jeri Reynolds, RN 859-323-8528 email@example.com |
|Sub-Investigator: Aman Chauhan, MD |
Lowell Anthony, MD
||Lowell Anthony, MD
||University of Kentucky
||Lowell Anthony, MD, Principal Investigator, University of Kentucky
History of Changes
|Other Study ID Numbers:
||December 21, 2016
||January 9, 2017
|Last Update Posted:
||April 24, 2017
|Individual Participant Data (IPD) Sharing Statement:
|Plan to Share IPD:
|Studies a U.S. FDA-regulated Drug Product:
|Studies a U.S. FDA-regulated Device Product:
|Product Manufactured in and Exported from the U.S.:
Additional relevant MeSH terms:
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasms, Glandular and Epithelial
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic