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

Phase 2

Completed

Conditions: Neuroendocrine Tumors

Interventions: Drug: fosbretabulin tromethamine

Registration Number: NCT02132468

Lead Sponsor: Mateon Therapeutics

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 18

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Number of Participants With Improved, Stable, or Worsened Change In Chromogranin A (CgA) Biomarker Levels From Baseline	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	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	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 Outcome Measures

Name	Time	Method
Number of Participants With Partial Response (PR), Progressive Disease (PD), or Stable Disease (SD) Based on RECIST 1.1	Baseline and 4 months	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.

Trial Locations

Locations (5): Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Stanford University School of Medicine
🇺🇸
Stanford, California, United States
Markey Cancer Center, Clinical Research Office
🇺🇸
Lexington, Kentucky, United States
Montefiore
🇺🇸
Bronx, New York, United States
Froedtert Hospital, Medicial College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States