A Ph 2 Study of Fosbretabulin in Subjects w Pancreatic or Gastrointestinal Neuroendocrine Tumors w Elevated Biomarkers (GI-NETorPNET)

A Ph 2 Study to Investigate the Safety and Activity of Fosbretabulin Tromethamine (CA4P) in the Treatment of Well-Differentiated, Low-to-Intermediate-Grade Unresectable, Recurrent or Metastatic PNET or GI-NET Neuroendocrine Tumors/Carcinoid With 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.

Study Overview

• Status: Completed
• Conditions: Neuroendocrine Tumors
• Intervention / Treatment: Drug: fosbretabulin tromethamine

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
  • Kentucky
    • Lexington, Kentucky, United States, 40356
      • Markey Cancer Center, Clinical Research Office
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital, Medicial College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

  ≤ 2.0 mg/dL (177 µmol/L)

• 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

Exclusion Criteria:

• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

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; Other Names: fosbretabulin, combretastatin A4-phosphate, CA4P

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Mateon Therapeutics

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: May 2, 2014
• First Submitted That Met QC Criteria: May 5, 2014
• First Posted (Estimate): May 7, 2014

Study Record Updates

• Last Update Posted (Actual): December 5, 2017
• Last Update Submitted That Met QC Criteria: October 31, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: PNET; neuroendocrine; carcinoid; GI-NET
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Fosbretabulin; Combretastatin
• Other Study ID Numbers: OX4218s