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2019 ASCO Annual Meeting!

Session: Gastrointestinal (Noncolorectal) Cancer

Type: Poster Session

Time: Monday June 3, 8:00 AM to 11:00 AM

Location: Hall A

Clinical efficacy and toxicity data on phase I study of fosbretabulin in combination with everolimus in neuroendocrine tumors.


Gastrointestinal (Noncolorectal) Cancer

2019 ASCO Annual Meeting

Abstract No:

Poster Board Number:
Poster Session (Board #219)

J Clin Oncol 37, 2019 (suppl; abstr 4114)

Author(s): Aman Chauhan, Susanne M. Arnold, Jianrong Wu, Rashmi T Nair, Stacey A. Slone, Emily Van Meter Dressler, Heather Flynn, Val R. Adams, Heidi Weiss, Mark Evers, Lowell Brian Anthony; University of Kentucky, Division of Medical Oncology, Lexington, KY; Markey Cancer Center, University of Kentucky, Lexington, KY; University of Kentucky, Lexington, KY; University of Kentucky Markey Cancer Center, Lexington, KY; Univ of Kentucky, Lexington, KY; University of Kentucky and Markey Cancer Center, Lexington, KY; University of Kentucky, lexington, KY

Abstract Disclosures


Background: Fosbretabulin, a synthetic, water-soluble, phosphorylated prodrug of the natural product combretastatin A4 (CA4P), initially isolated from the bark of the South African bush willow, Combretum caffrum, is the lead compound in a class of agents termed vascular disrupting agents (VDAs). Everolimus, an mTOR inhibitor, is FDA approved for the management of well-differentiated NETs. A Phase I trial combining fosbretabulin and everolimus to determine the recommended Phase II trial dose (RP2D), safety data and early clinical efficacy in metastatic GEPNET patients was conducted. Methods: An investigator-initiated, single center, open-label, phase I study involving GEPNETs incorporated partial order continual reassessment method (PO-CRM) to define the dose escalation. The primary objective was to establish the maximum tolerated dose (MTD) of the combination of everolimus and fosbretabulin in NETs that have progressed after at least one prior regimen for metastatic disease. Secondary objective included identifying the safety profile of the combination using NCI CTCAE4 reporting criteria. Patients received daily oral everolimus (2.5 mg, 5 mg, 7.5 mg, and 10 mg). Fosbretabulin was administered IV 60 mg/m2 either q3 weekly or q weekly based on PO-CRM. Patients were treated for 12 weeks with all combinations. RECIST 1.1 was used to evaluate radiological responses at 3 month. Results: Of the 17 patients enrolled, 16 completed the 12-week trial. One patient was not evaluable due to noncompliance. No DLTs were observed at day 21. The highest dose of 10 mg daily oral everolimus in combination with weekly 60mg/m2 IV fosbretabulin is the RP2D. No grade 4 or 5 toxicities were noted. Grade 3 toxicities were seen in 5 patients; abdominal pain and hyperglycemia (not related to study drug), fatigue (possibly related), decreased lymphocyte count and anemia (related). Several patients had delay in treatment due to grade 2 AE’s (GI symptoms, rash, thrombocytopenia) and one patient was unable to complete treatment due to pneumonitis. All evaluable patients except one had stable disease at 3 months. One patient showed SD but non target lesion demonstrated PD. One patient had > 30% decrease in tumor size but overall sum of lesions showed SD. A detailed table with all grade toxicities and waterfall plot of RR will be presented at the meeting. Conclusions: Ten mg PO daily everolimus plus 60 mg/m2 fosbretabulin IV weekly is the RP2D. Early clinical data suggests clinical activity and stable disease in all but one patient at 3 months. Clinical trial information: NCT0301429.

Other Abstracts in this Sub-Category:


1. Prospective randomized phase II trial of pazopanib versus placebo in patients with progressive carcinoid tumors (CARC) (Alliance A021202).

Meeting: 2019 ASCO Annual Meeting Abstract No: 4005 First Author: Emily K. Bergsland
Category: Gastrointestinal (Noncolorectal) Cancer - Neuroendocrine/Carcinoid


2. An open label, single-arm, two-stage, multicenter, phase II study to evaluate the efficacy and safety of TLC388 as second-line treatment in subjects with poorly differentiated neuroendocrine carcinomas (TCOGT1Z14).

Meeting: 2019 ASCO Annual Meeting Abstract No: 4101 First Author: Ming-Huang Chen
Category: Gastrointestinal (Noncolorectal) Cancer - Neuroendocrine/Carcinoid


3. A phase I study of oncolytic immunotherapy of metastatic neuroendocrine tumors using intralesional rose bengal disodium: Cohort 1 results.

Meeting: 2019 ASCO Annual Meeting Abstract No: 4102 First Author: Timothy Jay Price
Category: Gastrointestinal (Noncolorectal) Cancer - Neuroendocrine/Carcinoid