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

• ClinicalTrials.gov Identifier: NCT02132468
• Recruitment Status: Completed
• First Posted: May 7, 2014
• Results First Posted: October 19, 2017
• Last Update Posted: December 5, 2017
• Sponsor: Mateon Therapeutics
• Information provided by (Responsible Party): Mateon Therapeutics

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Neuroendocrine Tumors	Drug: fosbretabulin tromethamine	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: September 2014
• Actual Primary Completion Date: June 2016
• Actual Study Completion Date: August 2016

Arms and Interventions

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 Name: fosbretabulin, combretastatin A4-phosphate, CA4P

Outcome Measures

Primary Outcome Measures :

1. 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%.
2. 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%.
3. 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 Outcome Measures :

1. Number of Participants With Partial Response (PR), Progressive Disease (PD), or Stable Disease (SD) Based on RECIST 1.1 [ Time Frame: 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.

Eligibility Criteria

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

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)

Contacts and Locations

Locations

United States, California

Stanford University School of Medicine

Stanford, California, United States, 94305

United States, Kentucky

Markey Cancer Center, Clinical Research Office

Lexington, Kentucky, United States, 40356

United States, New York

Montefiore

Bronx, New York, United States, 10467

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

United States, Wisconsin

Froedtert Hospital, Medicial College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Mateon Therapeutics

More Information

• Responsible Party: Mateon Therapeutics
• ClinicalTrials.gov Identifier: NCT02132468 History of Changes
• Other Study ID Numbers: OX4218s
• First Posted: May 7, 2014
• Results First Posted: October 19, 2017
• Last Update Posted: December 5, 2017
• Last Verified: October 2017

Keywords provided by Mateon Therapeutics:

PNET; GI-NET; neuroendocrine; carcinoid

Additional relevant MeSH terms:

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Fosbretabulin; Combretastatin; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action