A Ph 2 Study Of Fosbretabulin In Subjects W Pancreatic Or Gastrointestinal Neuroendocrine Tumors W Elevated Biomarkers

Study Overview

A Ph 2 Study of Fosbretabulin in Subjects w Pancreatic or Gastrointestinal Neuroendocrine Tumors w Elevated Biomarkers

This study will investigate the safety, symptoms and biomarker response of subjects with biopsy-proven well-differentiated, low-to-intermediate-grade, unresectable, or metastatic pancreatic neuroendocrine tumors (PNETs) or or Gastrointestinal Neuroendocrine tumors (GI-NETs) with elevated biochemical markers who have relapsed during or after receiving prior standard of care therapies, including octreotide, chemotherapy or targeted therapy.

Subjects enrolled in this PNET/GI-NET study (OX4218s) will receive weekly dosing with fosbretabulin for up to 3 cycles or approximately 9 weeks.

Neuroendocrine Tumors

DRUG: fosbretabulin tromethamine

OX4218s

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2014-05-02	Results First Submitted 2017-09-21	Last Update Submitted that met QC Criteria 2017-10-31
First Submitted that Met QC Criteria 2014-05-05	Results First Submitted that Met QC Criteria 2017-09-21	Last Update Posted (ACTUAL) 2017-12-05
First Posted (ACTUAL) 2014-05-07	Results First Posted 2017-10-19	Last Verified 2017-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: fosbretabulin tromethamine Fosbretabulin 90 mg/vial; 60 mg/m2, IV infusion over 10 minutes; 1x/wk; three 3-week cycles	DRUG: fosbretabulin tromethamine 60 mg/m2, IV on Day 1, 8 and 15 of a 3-week cycle; 3 cycles or until progression or unacceptable toxicity

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: fosbretabulin tromethamine

Fosbretabulin 90 mg/vial; 60 mg/m2, IV infusion over 10 minutes; 1x/wk; three 3-week cycles

DRUG: fosbretabulin tromethamine

60 mg/m2, IV on Day 1, 8 and 15 of a 3-week cycle; 3 cycles or until progression or unacceptable toxicity

Primary Outcome Measures	Measure Description	Time Frame
Number of Participants With Improved, Stable, or Worsened Change In Chromogranin A (CgA) Biomarker Levels From Baseline	The mean change from baseline in chromogranin A (CgA) biomarker level is considered improved if a 25% reduction occurs and worsened if the mean change from baseline is increased by 25%.	Baseline and 4 months
Number of Participants With Improved, Stable, or Worsened Change In 5-hydroxyindoleacetic Acid (5-HIAA) Biomarker Levels From Baseline	The mean change from baseline in 5-hydroxyindoleacetic acid (5-HIAA) biomarker level is considered improved if a 25% reduction occurs and worsened if the mean change from baseline is increased by 25%.	Baseline and 4 months
Number of Participants With Improved, Stable, or Worsened Change In Serotonin Biomarker Levels From Baseline	The mean change from baseline in serotonin biomarker level is considered improved if a 25% reduction occurs and worsened if the mean change from baseline is increased by 25%.	Baseline and 4 months

Secondary Outcome Measures	Measure Description	Time Frame
Number of Participants With Partial Response (PR), Progressive Disease (PD), or Stable Disease (SD) Based on RECIST 1.1	The objective response rate (complete response, partial response, progressive disease, or stable disease) was determined by the investigator assessment of the participant's CT or MRI using Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1) for target lesions. Partial Response (PR) is when there is at least 30% decrease in sum of the longest diameter of the target lesions. Progressive Disease (PD) is when there is at least 20% increase in the sum of the longest diameter of the target lesions, as well as an absolute increase of at least 5 mm (including appearance of new lesions). Stable Disease (SD) is when there neither a PR nor PD is noted.	Baseline and 4 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Ability to read, understand and provide written consent to participate in the study
Age ≥ 18 years
Biopsy-proven well-differentiated, low-to-intermediate-grade PNET or GI-NET with elevated (> ULN) biomarkers (serotonin, 5-hydroxyindoleacetic acid (5-HIAA), chromogranin A (CgA), neurokinin A, and neuron-specific enolase (NSE))
Life expectancy > 12 weeks
Must have received or may still be receiving one or more therapies including octreotide or serotonin synthesis inhibitor (SSI) or other somatostatin analogues
Confirmed progressive disease within 18 months of enrollment on study
Recovered from prior radiation therapy or surgery
Eastern Cooperative Oncology Group (ECOG) performance score 0-2
Absolute neutrophil count (ANC) ≥ 1,500/µL (without growth factors)
Platelet count ≥ 100,000/µL
Adequate renal function as evidenced by serum creatinine

Adequate hepatic function: serum total bilirubin ≤ 2X greater than the upper limit of normal (ULN) (≤ 3X ULN in subjects with liver metastases), aspartate aminotransferase) AST) / alanine aminotransferase (AST) ≤ 2X the ULN for the local reference lab (≤ 5X the ULN for subjects with liver metastases)
Disease that can be assessed (evaluable) with imaging (CT, MRI, PET, radionuclide imaging or other imaging modality)
Women of childbearing potential as well as fertile men and their partners must use an effective method of birth control

Inadequately controlled hypertension defined as BP > 150/100 mm Hg despite medication
Prior history of hypertensive crisis or hypertensive encephalopathy
Recent history (within 6 months of start of screening) of unstable angina pectoris pattern, myocardial infarction (including non-Q wave MI), or NYHA (New York Heart Association) Class III and IV Congestive Heart Failure (CHF)
Subjects who have clinical evidence of carcinoid-induced heart disease
History of prior cerebrovascular accident (CVA), including transient ischemic attach (TIA)
Known central nervous system (CNS) disease except for treated brain metastasis
History of torsade de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (<60 bpm), heart block (excluding 1st degree block, being PR interval prolongation only), congenital long QT syndrome or new ST segment elevation or depression or new Q wave on ECG
Corrected QT interval (QTc) > 480 msec
Ongoing treatment with any drugs known to prolong the QTc interval, including anti-arrhythmic medications (stable regimen of antidepressants of the selective serotonin reuptake inhibitor (SSRI) class is allowed))
Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
Significant vascular disease or recent peripheral arterial thrombosis
Known intolerance of or hypersensitivity to fosbretabulin
History of solid organ transplant or bone marrow transplant
Any other intercurrent medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
High grade or poorly differentiated NET
NET tumor other than PNET or GI-NET
No elevated biomarker (>ULN) that can be followed
Received regional hepatic infusion therapy within 6 months of enrollment (RFA allowed >6 months prior to enrollment)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications

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