Delving into the Latest Updates on Orteronel with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Orteronel (JAN/USAN), TAK-700

Target

CYP17A1

Mechanism

CYP17A1 inhibitors(Steroid 17-alpha-hydroxylase inhibitors)

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication

Hormone-dependent prostate cancerMetastatic Prostate Carcinoma

Inactive Indication

Adenocarcinoma of prostateBone metastasesGranulosa Cell Tumor of the Ovary+ [4]

Originator Organization

Takeda Pharmaceutical Co., Ltd.

Active Organization

Millennium Pharmaceuticals, Inc.

Inactive Organization

Takeda Pharmaceutical Co., Ltd.

Excel Pharma Studies, Inc.Almac Clinical Services Ltd.

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC18H17N3O2

InChIKeyOZPFIJIOIVJZMN-SFHVURJKSA-N

CAS Registry566939-85-3

The main object of this multicenter, randomized, double-blind, placebo-controlled phase III trial is to assess impact of maintenance of orteronel on disease progression and hence on quality of life of patients with metastatic castration resistant prostate cancer pretreated with novel hormonal agents who have non-progressive disease after chemotherapy with a taxane.

Start Date19 Aug 2014

Sponsor / Collaborator

Swiss Group for Clinical Cancer Research

NCT02101684 / TerminatedPhase 2IIT

Open Label Phase II Clinical Trial of Orteronel (TAK-700) in Metastatic or Advanced Non-resectable Granulosa Cell Ovarian Tumors. The Greko II Study.

Granulosa Cell ovarian carcinoma is an infrequent subtype of neoplasia well differentiated from epithelial tumors. They account for 5% of all ovarian malignancies and, with an incidence of 0.4-1.2 cases per 100000 habitants, is considered as a rare disease.
Though most cases are identified at initial stages and can be cured through surgical resection, distant recurrences have been documented even 10 years after resecting the primary tumor. At advanced stage it is a lethal disease.
Unfortunately because of the low incidence of this disease randomized clinical trials are lacking. In fact current evidence for treatment is provided by case reports, retrospective studies and phase II clinical trials performed one decade ago.
Orteronel, a novel, orally active, selective inhibitor of 17,20-lyase, is being developed as an endocrine therapy for relevant hormone-sensitive cancers such as prostate cancer and breast cancer. Orteronel is expected to suppress sex hormone levels in both circulation and relevant hormone-dependent malignant tissue. Since sex hormone overproduction has been demonstrated in granulosa cell ovarian tumors and seems to play a major role in this disease, this study will assess the efficacy or orteronel treating such tumors.

Start Date01 Jun 2014

Sponsor / Collaborator

Takeda Pharmaceutical Co., Ltd.

NCT02054793 / WithdrawnPhase 1/2IIT

Phase Ib/II Study Evaluating Orteronel (Without Prednisone) Combined With Itraconazole In Men With Castration-Resistant Prostate Cancer (CRPC)

This research is being done to test the safety and anti-cancer activity of the combination of an investigational drug called orteronel, with a drug called itraconazole in the treatment of castration-resistant prostate cancer.
Orteronel is an investigational drug known as a 17,20-lyase enzyme inhibitor, meaning that it blocks the formation of male sex hormones.
Itraconazole is approved by the Food and Drug Administration (FDA) for the treatment of various fungal infections such as fingernail/toenail infections and other more serious fungal infections. While it has shown evidence of activity against prostate cancer in prior studies, it is not approved for use in cancer. The FDA is allowing the use of orteronel and itraconazole in this research study. In addition to its antifungal properties, itraconazole was discovered to function to block angiogenesis (blood vessel formation to tumors) to block a cellular pathway thought to be important in prostate cancer known as the Hedgehog pathway.
Investigators hypothesize that blocking male sex hormone production with orteronel will increase reliance on the Hedgehog pathway in prostate cancer cells which can then be blocked with itraconazole and that the combination of these two drugs will be more effective than either alone.

Start Date01 Jun 2014

Sponsor / Collaborator

The Johns Hopkins University

[+1]

100 Clinical Results associated with Orteronel

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100 Translational Medicine associated with Orteronel

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100 Patents (Medical) associated with Orteronel

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85

Literatures (Medical) associated with Orteronel

01 Nov 2024·European Urology Oncology

Correlation of Body Mass Index with Overall Survival Among Patients with Metastatic Hormone-sensitive Prostate Cancer: Analysis of Patient-level Data from SWOG-1216

Article

Author: Dorff, Tanya B ; Lerner, Seth P. ; Thompson, Ian M. ; Agarwal, Neeraj ; Dorff, Tanya B. ; Thompson, Ian M ; Gebrael, Georges ; Lara, Primo N ; Hage Chehade, Chadi ; Jo, Yeonjung ; Hussain, Maha H.A. ; Plets, Melissa ; Lerner, Seth P ; Hussain, Maha H A ; Lara, Primo N. ; Myint, Zin ; Gupta, Shilpa ; Narang, Arshit ; Swami, Umang ; Tangen, Catherine

Although obesity has been associated with better overall survival (OS) among patients with metastatic castration-resistant prostate cancer, its association with OS has not been extensively explored in metastatic hormone-sensitive prostate cancer (mHSPC). We conducted a post hoc exploratory analysis of patient-level data from the SWOG-1216 trial to determine whether baseline body mass index (BMI) is associated with better OS among patients with mHSPC. SWOG-1216 was an open-label, phase 3 trial that randomized patients newly diagnosed with mHSPC 1:1 to either androgen deprivation therapy (ADT) with orteronel (experimental arm) or ADT with bicalutamide (control arm). Of 1279 patients included in the analysis, 12 (0.9%) were underweight, 252 (19.7%) had normal BMI, 958 (74.9%) were overweight, and 57 (4.5%) were obese. Age, Gleason score, extent of disease burden, the incidence of visceral metastases, and treatment allocation were similar among the groups (p > 0.05), while differences in baseline prostate-specific antigen and Zubrod performance status were observed (p < 0.05). Median OS was 2.4, 5.5, 6.6, and 6.8 yr in the underweight, normal, overweight, and obese groups, respectively. After adjusting for prognostic variables, high BMI was associated with better OS (HR for each increment in BMI category: 0.829, 5% CI 0.68-0.98; p = 0.029). These findings need to be validated in other phase 3 trials. PATIENT SUMMARY: We analyzed data from a clinical trial to evaluate the association between body mass index (BMI) and overall survival among patients with metastatic hormone-sensitive prostate cancer. We found that in this group of patients, the risk of death was lower for patients with higher BMI.

01 Oct 2024·European urology oncology

Three- and Seven-month Prostate-specific Antigen Levels as Prognostic Markers for Overall Survival in Metastatic Hormone-sensitive Prostate Cancer: Results from SWOG S1216, a Phase 3 Randomized Trial of Androgen Deprivation Plus Orteronel or Bicalutamide

Article

Author: Lin, Daniel W ; Maughan, Benjamin L ; Parikh, Mamta ; Hussain, Maha H A ; Zibelman, Matthew R ; Paller, Channing J ; Lara, Primo N ; Quinn, David I ; Bryce, Alan H ; Lerner, Seth P ; Tangen, Catherine ; Pachynski, Russell K ; Zhang, Jingsong ; Jo, Yeonjung ; Cheng, Heather H ; Callis, Sam ; George, Saby ; Harzstark, Andrea ; Gupta, Shilpa ; Agarwal, Neeraj ; Dorff, Tanya B ; Thompson, Ian M

BACKGROUND:

A robust decrease in prostate-specific antigen (PSA) in response to androgen deprivation therapy (ADT) has been evaluated as a prognostic factor in patients with metastatic hormone-sensitive prostate cancer (mHSPC) since 2006, but the treatment of mHSPC has since evolved to include intensified therapy.

OBJECTIVE:

We assessed the association of PSA levels at 3 (PSA-3mo) and 7 (PSA-7mo) mo with overall survival (OS) in patients with mHSPC treated with ADT combined with either bicalutamide or orteronel in the S1216 phase 3 clinical trial.

DESIGN, SETTING, AND PARTICIPANTS:

PSA responses to treatment of patients in the S1216 trial were categorized as: complete response (CR) if PSA was ≤0.2 ng/ml, partial response if PSA was >0.2 and ≤4 ng/ml, and no response (NR) if PSA was >4 ng/ml.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

A Cox analysis (adjusted for treatment arm and three stratification factors: performance status, severity of disease, and early vs late induction) was used for OS association. While PSA-7mo association was a prespecified objective, PSA-3mo association was also evaluated.

RESULTS AND LIMITATIONS:

A total of 1251 and 1231 patients from the S1216 study were evaluable for PSA-3mo and PSA-7mo, respectively. A PSA-7mo CR was associated with improved OS compared with NR (HR: 0.20; p < 0.0001). A PSA-3mo CR showed a similar association to NR (HR: 0.34; p < 0.0001). The association of a PSA response with survival did not differ by treatment arm at either time point.

CONCLUSIONS:

The PSA-3mo and PSA-7mo responses were strongly associated with OS; taken with other emerging prognostic biomarkers, these markers may allow for early identification of patients at the highest risk of death, aid with counseling in clinical practice, and permit design of future clinical trials targeting these patients.

PATIENT SUMMARY:

A low prostate-specific antigen level at 3 or 7 mo after starting treatment for metastatic hormone-sensitive prostate cancer predicts longer survival regardless of the first treatment given with androgen deprivation therapy.

01 Sep 2024·Prostate cancer and prostatic diseases

Markers of bone metabolism and overall survival in men with bone-metastatic hormone sensitive prostate cancer (HSPC): A subset analysis of SWOG S1216, a phase III trial of androgen deprivation with or without orteronel

Article

Author: Lara, Primo N ; Gertz, Erik ; Goldkorn, Amir ; Twardowski, Przemyslaw ; Quinn, David I ; Mayerson, Edward ; Agarwal, Neeraj ; Parikh, Mamta ; Tangen, Catherine ; Thompson, Ian ; van Loan, Marta ; Hussain, Maha ; Zhang, Jingsong ; Gupta, Shilpa ; LeBlanc, Michael

BACKGROUND:

Circulating biomarkers of bone metabolism are significantly associated with overall survival (OS) in men with advanced prostate cancer. In the SWOG S1216 phase III trial, we showed that elevated bone biomarkers are significantly associated with an increased risk of death in hormone-sensitive prostate cancer (HSPC) regardless of the status of bone metastases, identifying three risk groups with differential OS outcomes based on bone biomarker status. Here we report the association of bone biomarkers with OS in men with HSPC and documented skeletal metastases as part of a planned subset analysis of S1216.

METHODS:

Bone resorption [C-telopeptide (CTx); Pyridinoline (PYD)] and bone formation markers [C-terminal collagen propeptide (CICP); bone alkaline phosphatase (BAP)] were assessed in blood from men with bone metastatic HSPC. Patients were randomly divided into training (n = 238) and validation (n = 475) sets. In the training set, recursive partitioning that maximizes discrimination of OS was used to identify the dichotomous cut-point for each biomarker and for a combination of biomarker split points to define prognostic groups. In the validation set, Cox proportional hazards models were used to assess the impact of biomarkers on OS, adjusted for patient and tumor characteristics.

RESULTS:

Of 1279 men, 713 had both baseline bone metastases and evaluable bone biomarkers. Patient characteristics were similar between the overall population and the subset with bone metastases. Elevated levels of CICP, CTX, and PYD were strongly prognostic for OS. Hazard ratios (95% CI) for OS adjusted for treatment arm and baseline clinical variables were: BAP-1.31 (0.93, 1.84), p = 0.12; CICP-1.58 (1.09, 2.29), p < 0.02; CTx - 1.55 (1.12, 2.15), p = 0.008; and PYD-1.66 (1.27, 2.217), p = 0.0002. There was no evidence of interaction between elevated biomarkers and treatment (all p > 0.2). Recursive partitioning algorithms identified four groups of patients with differential OS outcomes based on bone biomarkers, adjusted for baseline clinical variables, with median OS ranging from 2.3 years (highest risk group) to 7.5 years (lowest risk group).

CONCLUSIONS:

In this planned S1216 subset analysis of men with HSPC and bone metastases, elevated serum markers of bone metabolism were significantly associated with worse OS. Bone biomarker levels alone and in combination with patient and tumor characteristics identify unique subsets of men with differential OS outcomes.

CLINICALTRIALS:

GOV IDENTIFIER:

NCT01809691.

1

News (Medical) associated with Orteronel

04 Aug 2023

·www.drugs.com

FRIDAY, Aug. 4, 2023 -- For metastatic castration-sensitive prostate cancer (mCSPC), overall survival and progression-free survival are similar for Black and White patients receiving first- or second-generation androgen receptor pathway inhibitors within a clinical trial, according to a study published online Aug. 1 in JAMA Network Open . Nicolas Sayegh, M.D., from the University of Utah in Salt Lake City, and colleagues conducted a secondary analysis of patient-level data of a prospective phase 3 randomized clinical trial including patients with newly diagnosed mCSPC to compare survival outcomes by race. Patients receiving androgen deprivation therapy were randomly assigned to receive orteronel 300 mg orally twice daily (experimental group) or bicalutamide 50 mg orally daily (control group). Data were included for 1,313 participants: 10 and 82 percent identified as Black and White, respectively, with an equal racial distribution between the treatment groups. The researchers found that Black and White patients had similar median progression-free survival (2.3 years versus 2.9 years) and overall survival (5.5 years versus 6.3 years) at a median follow-up of 4.9 years. After adjustment for known prognostic factors, the multivariable analysis confirmed similar progression-free and overall survival. There was no interaction observed between race and treatment. "These results support the hypothesis that equitable access to care as available in a clinical trial setting negates disparities in outcomes previously associated with Black patient populations," the authors write. Several authors disclosed ties to the biopharmaceutical industry. Abstract/Full Text Posted August 2023

Phase 3Clinical Result

100 Deals associated with Orteronel

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External Link

KEGG	Wiki	ATC	Drug Bank
D10146	Orteronel	-	DB12066

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hormone-dependent prostate cancer	Phase 3	US	Millennium Pharmaceuticals, Inc.	08 Mar 2013
Metastatic Prostate Carcinoma	Phase 3	US	Millennium Pharmaceuticals, Inc.	08 Mar 2013
Metastatic castration-resistant prostate cancer	Phase 3	US	Millennium Pharmaceuticals, Inc.	01 Oct 2010
Metastatic castration-resistant prostate cancer	Phase 3	JP	Millennium Pharmaceuticals, Inc.	01 Oct 2010
Metastatic castration-resistant prostate cancer	Phase 3	AU	Millennium Pharmaceuticals, Inc.	01 Oct 2010
Metastatic castration-resistant prostate cancer	Phase 3	AT	Millennium Pharmaceuticals, Inc.	01 Oct 2010
Metastatic castration-resistant prostate cancer	Phase 3	BY	Millennium Pharmaceuticals, Inc.	01 Oct 2010
Metastatic castration-resistant prostate cancer	Phase 3	BE	Millennium Pharmaceuticals, Inc.	01 Oct 2010
Metastatic castration-resistant prostate cancer	Phase 3	BR	Millennium Pharmaceuticals, Inc.	01 Oct 2010
Metastatic castration-resistant prostate cancer	Phase 3	BG	Millennium Pharmaceuticals, Inc.	01 Oct 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


SWOG-1216 (ASCO2023) Manual	Phase 3	Prostatic Cancer	1,279	ADT±orteronel (Black patients)	ejiggpiuzp(vcytnnpwso) = PSA responses (≤ 0.2 ng/mL) at month 7 were similar in both groups. zucabewjav (oxzeznlinn ) View more	Positive	31 May 2023
				ADT±orteronel (White patients)
NCT01809691 (S1216 \| SWOG S1216, ASCO2023)	Phase 3	Metastatic castration-resistant prostate cancer	1,279	Orteroneleronel	hhzyeivpdb(jocmzlfhra) = lmrgdkgxki yzzgcykqeo (cqaabvlgin ) View more	-	31 May 2023
				Bicalutamidetamide	hhzyeivpdb(jocmzlfhra) = ypwwjqqlis yzzgcykqeo (cqaabvlgin ) View more
NCT01809691 (S1216 \| SWOG S1216, ASCO2023)	Phase 3	Castration-Resistant Prostatic Cancer	1,313	Androgen deprivation + Orteronel	xcveutbjlc(lfidpucdtb): HR = 1.58 (95% CI, 1.09 - 2.29) View more	-	31 May 2023
				Androgen deprivation
NCT01546987 (CTgov)	Phase 3	Prostatic Cancer	239	Radiation therapy (ADT + RT)	hsgnrxzdvl(csazbryqyx) = qottxwqybz umokxhjslm (felznnokon, gupchydelr - alhkznqwji) View more	-	18 Apr 2023
				Radiation therapy+TAK-700 (TAK-700 + ADT + RT)	hsgnrxzdvl(csazbryqyx) = xvjrhvgfqo umokxhjslm (felznnokon, nzmouvhhud - pizxspxtrd) View more
Pubmed \| J Clin Oncol	Phase 3	Hormone-dependent prostate cancer	-	Orteronel + ADT	vfzhlirswj(xamastgjan) = agsbkktfar kjligbyxjw (ltbqkijcki ) View more	Negative	01 Oct 2022
				Bicalutamide + ADT	vfzhlirswj(xamastgjan) = iofcgrlafz kjligbyxjw (ltbqkijcki ) View more
NCT01809691 (S1216 \| SWOG S1216 \| SWOG-1216 \| SWOG 1216, CTgov)	Phase 3	Hormone-dependent prostate cancer \| Metastatic Prostate Carcinoma	1,313	TAK-700 LHRH agonist+TAK-700+Leuprolide (LHRHa + TAK-700)	mieznlpqft(mzfhbjakuy) = qtzrmghcqi denlizpftn (rxwljiysyj, uhfyopcvwh - cydggdztyb) View more	-	08 Sep 2022
				Bicalutamide (LHRHa + Bicalutamide)	mieznlpqft(mzfhbjakuy) = finqiuspdk denlizpftn (rxwljiysyj, axxqobmwil - vchaqnzxjt) View more
PS11-29 (SABCS2021)	Phase 2	Metastatic Triple-Negative Breast Carcinoma androgen receptor (AR)	26	Orteronel 300 mg PO BID	xjztbskede(buqdvllhle) = 4 patients reporting SAEs (G2 pneumonitis, G2 chest pain and G2 peripheral edema, G4 prolonged QT and G4 hypokalemia) lrabaeukzx (gtffualvjq ) View more	Negative	15 Feb 2021
NCT01084655 (CTgov)	Phase 1/2	Metastatic castration-resistant prostate cancer	38	TAK-700+Prednisone+Docetaxel (Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone)	criaatrsvf(tgspparxve) = huqjkyfnvp bpykflmint (bbgmldsnqi, kfuqfknhlm - wewkhqahac) View more	-	30 Jul 2019
				TAK-700+Prednisone+Docetaxel (Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone)	criaatrsvf(tgspparxve) = ptlfyhignn bpykflmint (bbgmldsnqi, xlczegffeh - ycyyamudua) View more
NCT01193257 (ELM-PC 5, CTgov)	Phase 3	Metastatic castration-resistant prostate cancer	1,099	Orteronel Placebo+Prednisone (Placebo + Prednisone)	rcpwwthweg(oerjpeupap) = ztkqyhbijy ejhalzasti (ovcduajzrb, qjsvganhnk - mfjljcvdbm) View more	-	19 Dec 2018
				Orteronel+Prednisone (Orteronel + Prednisone)	rcpwwthweg(oerjpeupap) = vhhhlwcqie ejhalzasti (ovcduajzrb, loetterwog - nloigwenik) View more
NCT01809691 (S1216 \| SWOG S1216, ESMO2018)	Phase 3	Castration-Resistant Prostatic Cancer	1,313	Orteroneleronel	ctaajmuwch(hxbchulche) = vsetojopyy xsbscffsjo (crcwwcrdfv ) View more	-	22 Oct 2018