Delving into the Latest Updates on Ombrabulin Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Ombrabulin, Ombrabulin hydrochloride (JAN)

+ [7]

Target

Tubulin

Mechanism

Tubulin inhibitors

Therapeutic Areas

NeoplasmsOther DiseasesEndocrinology and Metabolic Disease+ [2]

Active Indication-

Inactive Indication

Advanced Malignant Solid NeoplasmLocally Advanced Soft Tissue Sarcomametastatic non-small cell lung cancer+ [2]

Originator Organization

Ajinomoto Co., Inc.

Active Organization-

Inactive Organization

Sanofi SA

Sanofi

Drug Highest PhasePendingPhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC21H27ClN2O6

InChIKeyUQNRTPFLTRZEIM-MRWUDIQNSA-N

CAS Registry253426-24-3

View All Structures (2)

Primary Objective:
- To demonstrate an improvement in Progression-Free Survival (PFS) for Ombrabulin versus placebo in patients with platinum-sensitive recurrent ovarian cancer (OC) treated with paclitaxel and carboplatin.
Secondary Objectives:
To compare the overall survival (OS) between the 2 treatment arms
To compare the objective response rate (RR) between the 2 treatment arms

Start Date01 May 2011

Sponsor / Collaborator

Sanofi SA

NCT01263886 / CompletedPhase 2

A Multinational, Randomized, Double Blind, Controlled Phase II Trial of Ombrabulin With Taxane and Platinum Combination Administered Every Three Weeks, in First Line Treatment of Patients Metastatic Non-small Cell Lung Cancer

Primary Objective:
To demonstrate progression free survival (PFS) improvement for ombrabulin compared to placebo, in combination with taxane and platinum, as first line treatment for patients with metastatic non-small cell lung cancer (NSCLC).
Secondary Objective:
To determine overall survival (OS), overall response rate (ORR) according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria, safety, and evaluate potential biomarkers, pharmacokinetic (PK) analysis of ombrabulin and its main metabolite, RPR258063, using a population approach.

Start Date01 Feb 2011

Sponsor / Collaborator

Sanofi SA

NCT01293630 / CompletedPhase 1

An Open-label, Dose-escalation, Safety and Pharmacokinetics Phase I Study of Ombrabulin in Combination With Paclitaxel and Carboplatin Every 3 Weeks in Patients With Advanced Solid Tumors

The primary objective of the study is to determine the maximum tolerated dose (MTD) based on the incidence of dose limiting toxicity (DLT) and the maximum administered dose (MAD) of ombrabulin combined with paclitaxel and carboplatin administered every 3 weeks in patients with advanced solid tumors.
Secondary Objectives:
To assess the overall safety profiles of the combination therapy
To characterize the pharmacokinetic profile of ombrabulin, its active metabolite RPR 258063, paclitaxel, and carboplatin when used in combination
To document the objective tumor response

Start Date01 Jan 2011

Sponsor / Collaborator

Sanofi

100 Clinical Results associated with Ombrabulin Hydrochloride

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100 Translational Medicine associated with Ombrabulin Hydrochloride

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100 Patents (Medical) associated with Ombrabulin Hydrochloride

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40

Literatures (Medical) associated with Ombrabulin Hydrochloride

01 Apr 2024·International Journal of Gynecologic Cancer

Phase I study of ombrabulin in combination with paclitaxel and carboplatin in Japanese patients with advanced solid tumors

Article

Author: Matsumoto, Koji ; Fujiwara, Keiichi ; Sunaga, Yoshinori ; Ecstein-Fraisse, Evelyne

ObjectivesTo evaluate the maximum tolerated dose/maximum administered dose, safety, pharmacokinetic, and efficacy profiles of ombrabulin combined with paclitaxel and carboplatin in Japanese patients with solid tumors.MethodsOmbrabulin (25, 30, or 35 mg/m2) combined with paclitaxel (175 or 200 mg/m2) and carboplatin (AUC5 or AUC6) was administered by intravenous infusion once every 3 weeks to patients with advanced solid tumors, including cervical, ovarian, and uterine cancers. The maximum tolerated dose/maximum administered dose was defined based on the dose-limiting toxicity at cycle 1. Efficacy was assessed based on Response Evaluation Criteria In Solid Tumors (RECIST).ResultsIn total, 18 patients were recruited for this dose escalation study. One out of six patients treated with the highest doses of combination of ombrabulin (35 mg/m2), paclitaxel (200 mg/m2), and carboplatin (AUC6) presented a dose-limiting toxicity consisting of grade 3Escherichiaurinary tract infection. This dose was defined as the maximum tolerated dose of ombrabulin. The most frequent treatment-emergent adverse events were alopecia (83.3%), neutropenia and fatigue (72.2% each), decreased appetite, nausea, diarrhea, arthralgia, and myalgia (66.7% each). The grade 3–4 treatment-emergent adverse events included neutropenia (61.1%),Escherichiaurinary tract infection, drug hypersensitivity, syncope, pulmonary embolism, and hydronephrosis (one patient each). In efficacy evaluation, seven patients achieved partial response or better (38.9%), including one complete response, and seven of 18 patients had stable disease (38.9%). Pharmacokinetic profiles in this Japanese study were comparable with those observed in the previous study without Japanese patients.ConclusionsAlthough the maximum tolerated dose/maximum administered dose of ombrabulin (35 mg/m2) with taxane-platinum combination may be tolerable in Japanese patients in the first cycle, the dosages in the repeated treatment should be carefully selected for further study.Trial registration numberNCT01293630.

01 Apr 2018·Japanese Journal of Clinical OncologyQ4 · MEDICINE

Phase 1 study of ombrabulin in combination with docetaxel and cisplatin in Japanese patients with advanced solid tumors

Q4 · MEDICINE

Article

Author: Ecstein-Fraisse, Evelyne ; Horio, Yoshitsugu ; Nishio, Makoto ; Hida, Toyoaki ; Satouchi, Miyako ; Sunaga, Yoshinori ; Horiike, Atsushi

BACKGROUNDThe combination use of the vascular disrupting agent ombrabulin with chemotherapeutic agents was previously shown to be highly synergistic in preclinical models.METHODSIn this dose-escalation study of ombrabulin (15.5-35 mg/m2) in combination with docetaxel (60 or 75 mg/m2) and cisplatin (75 mg/m2), agents were administered 24 h apart every 3 weeks to Japanese patients with advanced solid tumors. The study was designed and conducted in a 3 + 3 manner. Safety, tumor response and pharmacokinetics were evaluated.RESULTSEleven patients with non small cell lung cancer as the primary tumor were treated. Two patients out of five had dose limiting toxicities (DLTs) in Cycle 1 at the starting doses of ombrabulin 15.5 mg/m2, docetaxel 60 mg/m2 and cisplatin 75 mg/m2. Thus, dose escalation was terminated. The first dose level was re-evaluated in six patients who received prophylactic granulocyte-colony stimulating factor (G-CSF). However, because of the occurrence of DLTs in Cycle 1 in two patients out of six, the study was led to the premature termination without pursued upper dose level. Partial response was observed in four patients out of 11. Pharmacokinetic parameters of ombrabulin and cisplatin were not altered in this combination treatment, while docetaxel clearance decreased by ~40% compared to that observed with docetaxel monotherapy at the same dose (60 mg/m2).CONCLUSIONA combination regimen of ombrabulin with cisplatin and docetaxel was not feasible for Japanese patients owing to the occurrence of hematological and non-hematological DLTs at the initial dose level.CLINICAL TRIAL REGISTRATION IDClinicalTrials.gov number, NCT01095302.

01 May 2017·Gynecologic OncologyQ2 · MEDICINE

The development and use of vascular targeted therapy in ovarian cancer

Q2 · MEDICINE

Review

Author: Chase, Dana M ; Monk, Bradley J ; Chaplin, David J

Combination vascular-targeted therapies (VTTs) represent a promising approach for patients with platinum-resistant recurrent ovarian cancer (OC). VTTs include two mechanistically distinct classes of agents: anti-angiogenic agents (AAs) and vascular-disrupting agents (VDAs). AAs suppress growth of new tumor vasculature through inhibition of vascular endothelial growth factor (VEGF) and other pro-angiogenic molecules. Bevacizumab, a monoclonal antibody that binds to VEGF, has improved progression-free survival (PFS) when given with chemotherapy in patients with advanced OC. VDAs target the established tumor vascular network, inducing vessel occlusion, shutdown of circulation, and widespread necrosis within the tumor interior - a region often resistant to conventional chemotherapy and radiation. Tubulin-binding VDAs such as BNC105P, ombrabulin, and combretastatin A4-phosphate (CA4P) have been studied for the treatment of OC. These agents act by binding tubulin in the endothelial cells of tumor vessels, triggering cytoskeletal disruption, altering cellular shape, and destabilizing cell-cell junctions, which lead to increased vascular leakage and, ultimately, to disruption of blood flow. Fundamental differences between the vascular networks of tumors and those of normal tissues allow these agents to selectively reduce tumor circulation while having little effect on non-malignant tissues. Animal studies and clinical trials show enhanced efficacy when VDAs are combined with chemotherapy as well as AAs. The latter combination allows targeting of different aspects of the tumor vasculature, a strong rationale for combining these two drug classes into a single regimen. CA4P is the only VDA in active development for OC. In a phase II trial of patients with recurrent OC, CA4P added to bevacizumab improved PFS compared with bevacizumab alone. The phase II, placebo-controlled PAZOFOS trial (NCT02055690) is evaluating the effects of CA4P plus the anti-angiogenic agent pazopanib in recurrent OC. FOCUS, a phase II/III, placebo-controlled trial (NCT02641639), is currently evaluating CA4P plus bevacizumab and chemotherapy in platinum-resistant OC.

100 Deals associated with Ombrabulin Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D09787	Ombrabulin Hydrochloride	-	DB12882

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Locally Advanced Soft Tissue Sarcoma	Phase 3	IT	Sanofi	01 Jun 2008
Locally Advanced Soft Tissue Sarcoma	Phase 2	RS	Sanofi	01 Jun 2008
Locally Advanced Soft Tissue Sarcoma	Phase 2	ES	Sanofi	01 Jun 2008
Locally Advanced Soft Tissue Sarcoma	Phase 2	GB	Sanofi	01 Jun 2008
Locally Advanced Soft Tissue Sarcoma	Phase 2	FR	Sanofi	01 Jun 2008
Locally Advanced Soft Tissue Sarcoma	Phase 2	HU	Sanofi	01 Jun 2008
Locally Advanced Soft Tissue Sarcoma	Phase 2	IN	Sanofi	01 Jun 2008
Locally Advanced Soft Tissue Sarcoma	Phase 2	US	Sanofi	01 Jun 2008
Locally Advanced Soft Tissue Sarcoma	Phase 2	BE	Sanofi	01 Jun 2008
Locally Advanced Soft Tissue Sarcoma	Phase 2	BR	Sanofi	01 Jun 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01095302 (Pubmed \| Jpn J Clin Oncol) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	11	docetaxel+cisplatin+ombrabulin	(ofwcwmrfjw) = ucjpbdmvlu puoyzyqcbu (rzawfdsmbu ) View more	Negative	01 Apr 2018
NCT00968916 (Pubmed \| Cancer Chemother Pharmacol)	Phase 1	HR-positive/HER2-low Solid Tumors	15	Ombrabulin 15.5 mg/m(2)	(dugeuoukjb) = ngjbefvpjp cxchmjyqag (cbojpbhabd )	-	01 Mar 2014
NCT01293630 (ESMO2013) Manual	Phase 1	Advanced Malignant Solid Neoplasm	18	Paclitaxel+Carboplatin+Ombrabulin (dose-escalation)	(eooxjntteb) = ombrabulin 35 mg/m2, PTX 200 mg/m2 and CBDCA AUC6 qdhgsgyhkw (ixydaktlhc ) View more	Positive	01 Nov 2013
NCT01332656 (Opsalin, ASCO2013)	Phase 2	Platinum-Sensitive Ovarian Carcinoma	154	Ombrabulin 35 mg/m²	(otedpebzew) = zywoppauwo rjgzbxebgo (daohtkvzhg ) View more	Negative	20 May 2013
				Placebo	(otedpebzew) = oeaynpnbmh rjgzbxebgo (daohtkvzhg ) View more
NCT00699517 (ASCO2013)	Phase 3	Soft Tissue Sarcoma	355	Ombrabulin 25 mg/m²	(bavveesfyi) = xjvjoavpat hnpalpnbgr (hemamdjlmc ) View more	Negative	20 May 2013
				Placebo	(bavveesfyi) = wmobsxdmqn hnpalpnbgr (hemamdjlmc ) View more
NCT01193595 (ASCO2013)	Phase 1	HR-positive/HER2-low Solid Tumors	39	Ombrabulin	(dfmiethcom) = 1/39, 3% ydixymrmpi (qmymzzkysu ) View more	-	20 May 2013
				Bevacizumab