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

NCT02132468 | Completed Phase 2 Results

• 1 other identifier: OX4218s
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Neuroendocrine Tumors

Keywords

PNET; GI-NET; neuroendocrine; carcinoid

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• Number of Participants With Partial Response (PR), Progressive Disease (PD), or Stable Disease (SD) Based on RECIST 1.1

  Baseline and 4 months

Study Arms (1)

fosbretabulin tromethamine

EXPERIMENTAL

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

Drug: fosbretabulin tromethamine

Interventions

fosbretabulin tromethamine DRUG

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

Also known as: fosbretabulin, combretastatin A4-phosphate, CA4P

fosbretabulin tromethamine

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mateon Therapeutics: lead

Study Sites (5)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Markey Cancer Center, Clinical Research Office

Lexington, Kentucky, 40356, United States

Location

Montefiore

The Bronx, New York, 10467, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Froedtert Hospital, Medicial College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Neuroendocrine Tumors; Neuroectodermal Tumors, Primitive; Carcinoid Tumor

Interventions

fosbretabulin

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma

Results Point of Contact

• Title: Clinical Operations
• Organization: Mateon Therapeutics

ca@mateon.com

6506357000

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2014
• First Posted: May 7, 2014
• Study Start: September 1, 2014
• Primary Completion: June 1, 2016
• Study Completion: August 1, 2016
• Last Updated: December 5, 2017
• Results First Posted: October 19, 2017

Record last verified: 2017-10

Locations

US (5)