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
Overview
- Phase
- Phase 2
- Intervention
- fosbretabulin tromethamine
- Conditions
- Neuroendocrine Tumors
- Sponsor
- Mateon Therapeutics
- Enrollment
- 18
- Locations
- 5
- Primary Endpoint
- Number of Participants With Improved, Stable, or Worsened Change In Chromogranin A (CgA) Biomarker Levels From Baseline
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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.
Investigators
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
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)
Arms & Interventions
fosbretabulin tromethamine
Fosbretabulin 90 mg/vial; 60 mg/m2, IV infusion over 10 minutes; 1x/wk; three 3-week cycles
Intervention: fosbretabulin tromethamine
Outcomes
Primary Outcomes
Number of Participants With Improved, Stable, or Worsened Change In Chromogranin A (CgA) Biomarker Levels From Baseline
Time Frame: Baseline and 4 months
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%.
Number of Participants With Improved, Stable, or Worsened Change In 5-hydroxyindoleacetic Acid (5-HIAA) Biomarker Levels From Baseline
Time Frame: Baseline and 4 months
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%.
Number of Participants With Improved, Stable, or Worsened Change In Serotonin Biomarker Levels From Baseline
Time Frame: Baseline and 4 months
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%.
Secondary Outcomes
- Number of Participants With Partial Response (PR), Progressive Disease (PD), or Stable Disease (SD) Based on RECIST 1.1(Baseline and 4 months)