Clinical trial NCT02132468: A Ph 2 Study of Fosbretabulin in Subjects w Pancreatic or Gastrointestinal Neuroendocrine Tumors w Elevated Biomarkers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroendocrine Tumors
Keywords: PNET
GI-NET
neuroendocrine
carcinoid
Lead sponsor: Mateon Therapeutics
Sponsor class: INDUSTRY
First posted: 2014-05-07
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of Participants With Improved, Stable, or Worsened Change In Chromogranin A (CgA) Biomarker Levels From Baseline
timeFrame: Baseline and 4 months
measure: Number of Participants With Improved, Stable, or Worsened Change In 5-hydroxyindoleacetic Acid (5-HIAA) Biomarker Levels From Baseline
timeFrame: Baseline and 4 months
measure: Number of Participants With Improved, Stable, or Worsened Change In Serotonin Biomarker Levels From Baseline
timeFrame: Baseline and 4 months
Secondary outcomes:
measure: Number of Participants With Partial Response (PR), Progressive Disease (PD), or Stable Disease (SD) Based on RECIST 1.1
timeFrame: Baseline and 4 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Lexington
country: United States
facility: Markey Cancer Center, Clinical Research Office
state: Kentucky
city: Bronx
country: United States
facility: Montefiore
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Milwaukee
country: United States
facility: Froedtert Hospital, Medicial College of Wisconsin
state: Wisconsin
Study officials:
References: