Evidence map›Paper›PMID 27169564›Full record

Trial reportTargeted oncology2016

An Adaptive Study to Determine the Optimal Dose of the Tablet Formulation of the PARP Inhibitor Olaparib.

J Mateo, V Moreno, A Gupta, S B Kaye, E Dean, M R Middleton, M Friedlander, C Gourley, R Plummer, G Rustin and 8 more

Registry-linked trialAbstract readClinical Trial, Phase IRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Targeted oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00777582 (A Phase I, Randomised, 2 Period Cross Over Study to Determine the Comparative Bioavailability of Two Different Oral Formulations of AZD2281 in Cancer Patients With Advanced Solid Tumours), which is not on this map. Cited by 65 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 3 pooled it
–field-weighted citation impact
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.

NCT00777582 phase1active not recruitingnot on this map

A Phase I, Randomised, 2 Period Cross Over Study to Determine the Comparative Bioavailability of Two Different Oral Formulations of AZD2281 in Cancer Patients With Advanced Solid Tumours

TypeinterventionalSponsorAstraZenecaRan2008 to 2027Enrolled197ConditionsSolid TumorsArmsAZD2281
3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020
    Guideline
  3. Pooled it
  4. Trial
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  10. Sequence-Specific Pharmacokinetic and Pharmacodynamic Phase I/Ib Study of Olaparib Tablets and Carboplatin in Women's Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017
    Trial
  11. Review
  12. Article
  13. Article
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  19. Article
  20. Article

5 more citing papers are in PubMed but not listed here.

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

18 authors.

J MateoDrug Development Unit, The Royal Marsden/The Institute of Cancer Research, Downs Road, Sutton, SM2 5PT, UK.
V MorenoDrug Development Unit, The Royal Marsden/The Institute of Cancer Research, Downs Road, Sutton, SM2 5PT, UK.
A GuptaDepartment of Oncology, University of Oxford, Oxford, UK.
S B KayeDrug Development Unit, The Royal Marsden/The Institute of Cancer Research, Downs Road, Sutton, SM2 5PT, UK.
E DeanClinical Trials Unit, The Christie NHS Foundation Trust/University of Manchester, Manchester, UK.
M R MiddletonDepartment of Oncology, University of Oxford, Oxford, UK.
M FriedlanderPrince of Wales Clinical School, University of New South Wales, Prince of Wales Hospital, Randwick, Australia.
C GourleyUniversity of Edinburgh Cancer Research UK Centre, MRC IGMM, Edinburgh, UK.
R PlummerNorthern Centre for Cancer Care, Newcastle-upon-Tyne, UK.
G RustinMount Vernon Hospital, Northwood, UK.
C SessaOncology Institute of Southern Switzerland, Bellinzona, Switzerland.
K LeunenDepartment of Obstetrics and Gynecology, Division of Gynecologic Oncology, University Hospitals Leuven, Leuven, Belgium.
J LedermannUCL Hospitals and UCL Cancer Institute, London, UK.
H SwaislandAstraZeneca, Macclesfield, UK.
A FieldingAstraZeneca, Macclesfield, UK.
W BannisterPHASTAR, London, UK.
S NicumDepartment of Oncology, University of Oxford, Oxford, UK.
L R MolifeDrug Development Unit, The Royal Marsden/The Institute of Cancer Research, Downs Road, Sutton, SM2 5PT, UK. maria.bynoe@icr.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOlaparib is poorly soluble, requiring advanced drug delivery technologies for adequate bioavailability. Sixteen capsules/day are required for the approved 400 mg twice-daily dose; a tablet formulation was developed to reduce pill burden. This clinical trial evaluated the optimal dose and administration schedule of the tablet formulation. PATIENTS AND

methodsTwo stages of sequentially enrolled cohorts: stage 1, pharmacokinetic properties of tablet and capsule formulations were compared in patients with advanced solid tumours; stage 2, tablet dose escalation with expansion cohorts at doses/schedules of interest in patients with solid tumours and BRCAm breast/ovarian cancers.

resultsOlaparib 200 mg tablets displayed similar Cmax,ss, but lower AUCss and Cmin,ss than 400 mg capsules. Following multiple dosing, steady-state exposure with tablets ≥300 mg matched or exceeded that of 400 mg capsules. After dose escalation, while 400 mg twice daily was the tablet maximum tolerated dose based on haematological toxicity, 65 % of patients in the randomized expansion phase eventually required dose reduction to 300 mg. Intermittent tablet administration did not significantly improve tolerability. Tumour shrinkage was similar for 300 and 400 mg tablet and 400 mg capsule cohorts.

conclusionsThe recommended monotherapy dose of olaparib tablet for Phase III trials was 300 mg twice daily, simplifying drug administration from 16 capsules to four tablets per day. CLINICAL TRIAL NUMBER: NCT00777582 (ClinicalTrials.gov).

Indexed as

FemaleHumansMaleMaximum Tolerated DosePhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsolaparibPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase Inhibitors

Identifiers

PMID27169564

What OpenQuestion holds

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Registered trials

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.