Evidence map›Paper›PMID 32327394›Full record

Trial reportClinical genitourinary cancer2020

Phase 2 Study of Seviteronel (INO-464) in Patients With Metastatic Castration-Resistant Prostate Cancer After Enzalutamide Treatment.

Ravi A Madan, Keith T Schmidt, Fatima Karzai, Cody J Peer, Lisa M Cordes, Cindy H Chau, Seth M Steinberg, Helen Owens, Joel Eisner, William R Moore and 3 more

Open access · greenAbstract readClinical Trial, Phase II
In one paragraph

Trial report in Clinical genitourinary cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.4field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Steroidogenic cytochrome P450 17A1 structure and function.Molecular and cellular endocrinology · 2021
    Review
  6. Review
  7. Review
  8. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

Ravi A MadanGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Keith T SchmidtClinical Pharmacology Program, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Fatima KarzaiGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Cody J PeerClinical Pharmacology Program, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Lisa M CordesGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Cindy H ChauGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Seth M SteinbergBiostatistics and Data Management Section, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Helen OwensGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Joel EisnerInnocrin Pharmaceuticals Inc, Durham, NC.
William R MooreInnocrin Pharmaceuticals Inc, Durham, NC; Vizuri Health Sciences LLC, Fairfax, VA.
William L DahutGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
James L GulleyGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
William D FiggGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; Clinical Pharmacology Program, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. Electronic address: figgw@helix.nih.gov.
National Institutes of Health · USInnocrin Pharmaceuticals (United States) · US

Funding

Office of Collaborative BiostatisticsZIDSC007202 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI CHOO-WOSOBA, HYOYOUNG · 2009 to 2025
$14.5M
Drug Development for Prostate Cancer and other Metastatic ProcessesZIABC010547 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI FIGG, WILLIAM DOUGLAS · 2009 to 2025
$10.2M
Clinical trials employing cancer vaccine combination therapiesZIABC010945 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GULLEY, JAMES L. · 2009 to 2022
$9.6M
The Evaluation of Novel Therapeutics for Genitourinary MalignanciesZIASC010098 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI DAHUT, WILLIAM L. · 2009 to 2022
$7.6M
Evaluation of Immune-based Combinations in Prostate CancerZIABC011897 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MADAN, RAVI · 2019 to 2025
$3.1M
Development of Drugs That Target Prostate CancerZ01BC010547 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI FIGG, WILLIAM DOUGLAS · 2003 to 2008
$463k
Intramural NIH HHS Z01 BC010547
6 · The paper itself

Abstract

backgroundSeviteronel was being developed by Innocrin Pharmaceuticals as a selective cytochrome P450c17a (CYP17) 17,20-lyase (lyase) inhibitor and androgen receptor antagonist with activity against prostate cancer cells in vitro and in vivo. This open-label phase 2 clinical study evaluated the tolerability and efficacy of seviteronel in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with enzalutamide. PATIENTS AND

methodsPatients with mCRPC whose disease previously progressed while receiving enzalutamide therapy were divided into 2 cohorts on the basis of prior exposure to docetaxel. Seviteronel was administered without routine oral steroids either twice daily with dose titration (450 mg) or once daily without dose titration (600 or 750 mg). The primary objective was to determine the rate of significant prostate-specific antigen response (ie, decline of ≥ 50%) after 12 weeks of seviteronel therapy.

resultsSeventeen patients, with a median (range) age of 71 (60-92) years, were enrolled, with 8 patients having received prior docetaxel. Patients received a median of 2 cycles of treatment, with most patients discontinuing treatment because of toxicity related to the study drug. The most common adverse events included concentration impairment, fatigue, tremor, and nausea. Despite changes in dosing, the study was closed prematurely because of the high magnitude of toxicity. One (6%) of 17 patients experienced a significant decline in prostate-specific antigen.

conclusionSeviteronel was not generally well tolerated nor associated with significant clinical responses in patients with mCRPC who had previously received enzalutamide. Further investigation of single-agent seviteronel in this patient population is not warranted; however, studies investigating seviteronel with low-dose dexamethasone are ongoing in patients with androgen receptor-positive tumors.

Indexed as

AgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBenzamidesDrug Resistance, NeoplasmFollow-Up StudiesHumansMaleMiddle AgedNaphthalenesNitrilesPhenylthiohydantoinPrognosisProstatic Neoplasms, Castration-ResistantSurvival RateTriazolesBenzamidesenzalutamideNaphthalenesNitrilesPhenylthiohydantoinseviteronelTriazolesAcquired resistanceAndrogen receptorCYP17 inhibitormCRPCPharmacokinetics

Identifiers

PMID32327394
PMCPMC7415516
OpenAlexW3013013514

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.