Solid TumoursPhase 1NCT02093351

To Assess Safety and Effect of Olaparib on the Pharmacokinetics of Anastrozole, Letrozole & Tamoxifen, and Their Effect on Olaparib, in Patients With Advanced Solid Cancer

A Phase 1 study testing Olaparib, Tamoxifen and Anastrozole in people with Solid Tumours, run by AstraZeneca at 14 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This is an open-label 2-part Phase I study in patients with advanced solid tumours. Part A of the study (mandatory) will assess the effect of olaparib on the pharmacokinetics (PK) of anastrozole, letrozole and tamoxifen and vice versa; Part B will allow patients (if eligible) continued access to olaparib after the PK… Read more about this study

Who is it for?: Ages 18 to 130 years
Conditions the study is for: Solid Tumours
What is being tested?: Olaparib, Tamoxifen and Anastrozole
Type of treatment: Pill or oral medicine, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 79 participants
Where: 14 sitesin 5 countries
Study dates: 1 Sep 2014to 29 Apr 2019
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 130 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Provision of written informed consent prior to any study specific procedures
Male or female aged ≥18 years
Histological or cytological confirmation of any malignant solid tumour in an advanced or metastatic setting who meet one of the criteria below:
Patients should be resistant or refractory to standard treatment if such treatment exists OR
Patients for which no suitable effective standard therapy exists OR
Patients with advanced breast cancer for whom anastrozole, letrozole or tamoxifen are indicated may also enter the study (postmenopausal breast cancer patients will be eligible for any of the cohorts; however, premenopausal breast cancer patients will be eligible for the tamoxifen cohort only).

Show all 24Show fewer

Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
Haemoglobin (Hb) ≥10.0 g/dL with no blood transfusions in the past 28 days
Absolute neutrophil count (ANC) ≥1.5 x 109/L
Platelet count ≥100 x 109/L
Total bilirubin ≤1.5 x institutional upper limit of normal (ULN) (except in the case of Gilbert's disease)
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤2.5 x institutional ULN unless liver metastases are present, in which case they must be ≤5x ULN
Serum creatinine ≤1.5 x institutional ULN
Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
Patients must have a life expectancy ≥16 weeks
Evidence of non-childbearing status for women of childbearing potential, or postmenopausal status: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on Day 1 of Part A.
Postmenopausal is defined as:
Age ≥ 60 years
Age <60 years and amenorrheic for 1 year or more in the absence of chemotherapy and/or hormonal treatment
Luteinising hormone (LH), follicle stimulating hormone (FSH) and plasma oestradiol levels in the postmenopausal range for women under 60 years
Radiation-induced oophorectomy with last menses >1 year ago
Or surgical sterilisation (bilateral oophorectomy or hysterectomy)
Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment, and scheduled visits and examinations
Patients must be on stable concomitant medication regimen (with the exception of electrolyte supplements), defined as no change in medication or dose within 2 weeks prior to start of study treatment.

Who cannot join

Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff, its agents, and/or staff at the study site)
Previous enrolment in the present study
Exposure to an investigational product (IP) (including PARP inhibitor) within 30 days or 5 half lives (whichever is the longer) prior to enrolment
Prior chemotherapy within 3 weeks of study entry
Prior radiotherapy within 2 weeks of study entry
If prior endocrine treatment is given, adequate washout period is required: at least 2 weeks for anastrozole, at least 4 weeks for letrozole and at least 10 weeks for tamoxifen

Show all 17Show fewer

Resting ECG with QTc >470 msec detected on 2 or more time points within a 24 hour period, or family history of long QT syndrome. If ECG demonstrates QTc >470 msec, patient will be eligible only if repeat ECG demonstrates QTc <470 msec.
Patients who are receiving inhibitors or inducers of CYP3A4 unless washed out prior to start of study treatment.
Persistent toxicities (Common Toxicity Criteria for Adverse Events [CTCAE] grade ≥2) caused by previous cancer therapy, excluding alopecia and/or CTCAE grade 2 peripheral neuropathy
Patients with myelodysplastic syndrome/acute myeloid leukaemia
Major surgery within 2 weeks of starting study treatment: patients must have recovered from any effects of any major surgery
Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled seizures or active uncontrolled infection.
Patients unable to swallow orally administered medication and patients with gastrointestinal disorders or significant gastrointestinal resection likely to interfere with absorption of the study medication
Patients who have gastric, gastro-oesophageal, or oesophageal cancer
Pregnant or breastfeeding women
Patients with known active Hepatitis B or C, or human immunodeficiency virus (HIV).
Patients with a known hypersensitivity to olaparib (all cohorts), tamoxifen (Cohort 1) anastrozole (Cohort 2), letrozole (Cohort 3), or any of the excipients of these products.

Trial locations and contacts

14 sites in 5 countries.

Country

City, postcode or hospital

14 sites in 5 countries

Belgium6 sites

Research Site
Brussels, 1090
Research Site
Edegem, 2650
Research Site
Ghent, 9000
Research Site
Leuven, 3000
Research Site
Liège, 4000
Research Site
Wilrijk, 2610

Other trials in Belgium

United Kingdom4 sites

Research Site
London, SE1 9RT
Research Site
Manchester, M20 4BX
Research Site
Newcastle upon Tyne, NE7 7DN
Research Site
Sutton, SM2 5PT

Other trials in United Kingdom

Netherlands2 sites

Research Site
Amsterdam, 1081 HV
Research Site
Utrecht, 3584 CX

Other trials in Netherlands

Denmark1 site

Research Site
Herlev, 2730

Other trials in Denmark

France1 site

Research Site
Bordeaux, 33076

Other trials in France

About this study

Official title: An Open-Label, Non-randomised, Parallel Group, Multicentre, Phase I Study to Assess the Safety and Effect of Olaparib at Steady State on the Pharmacokinetics of the Anti-hormonal Agents Anastrozole, Letrozole and Tamoxifen at Steady State, and the Effect of the Anti-hormonal Agents on Olaparib, Following Administration in Patients With Advanced Solid Cancer

Conditions: Solid Tumours
Being tested: Olaparib, Tamoxifen, Anastrozole, Letrozole, Pharmacokinetic sampling
Keywords: oncology, cancer, tumour, neoplasm, anticancer drug, pharmacokinetics, olaparib, anastrozole, tamoxifen, letrozole,
Medical subject headings: Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OlaparibDrug
2 x 150mg tablets, twice daily Day 1-5, and Day 27 onwards (Cohort 1), Day 20 onwards (Cohort 2) or Day 39 onwards (Cohort 3)
TamoxifenDrug
60mg Tamoxifen once daily, Day 10 - Day 13; 20mg Tamoxifen once daily, Day 14 - Day 31
AnastrozoleDrug
1mg Anastrozole once daily Day 10 - Day 24
LetrozoleDrug
2.5mg Letrozole once daily Day 10 - Day 43
Pharmacokinetic samplingProcedure or surgery
Blood sampling over 12-24 hour period for pharmacokinetic analysis

Study groups in NCT02093351
Study group	Role	What they receive
Cohort 1 - Tamoxifen	Experimental	Olaparib-alone Steady state PK, Tamoxifen-alone steady state PK, Combined olaparib and Tamoxifen steady state PK. Receives: Drug: Olaparib; Drug: Tamoxifen; Procedure: Pharmacokinetic sampling
Cohort 2 - Anastrozole	Experimental	Olaparib-alone Steady state PK, Anastrozole-alone steady state PK, Combined olaparib and Anastrozole steady state PK. Receives: Drug: Olaparib; Drug: Anastrozole; Procedure: Pharmacokinetic sampling
Cohort 3 - Letrozole	Experimental	Olaparib-alone Steady state PK, Letrozole-alone steady state PK, Combined olaparib and Letrozole steady state PK. Receives: Drug: Olaparib; Drug: Letrozole; Procedure: Pharmacokinetic sampling

What is being measured

The primary outcome is the main question the study is designed to answer.

Effect of Olaparib on Exposure to Tamoxifen - Cmax ss
Tamoxifen, N-desmethyl tamoxifen (N-DMT) and endoxifen Cmax ss in the presence and absence of co-administered olaparib, and associated Cmax ss treatment ratios
Measured: Pre-dose and at 1, 2, 4, 5, 6, 8, 12 and 24 hours post-dose on Day 26 and Day 31
Effect of Tamoxifen on Exposure to Olaparib - Cmax ss
Olaparib Cmax ss in the presence and absence of co-administered tamoxifen, and associated Cmax ss treatment ratios
Measured: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 31
Effect of Olaparib on Exposure to Anastrozole - Cmax ss
Anastrozole maximum plasma concentration at steady state (Cmax ss) in the presence and absence of co-administered olaparib, and associated Cmax ss treatment ratios
Measured: Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 19 and Day 24
Effect of Anastrozole on Exposure to Olaparib - Cmax ss
Olaparib Cmax ss in the presence and absence of co-administered anastrozole, and associated Cmax ss treatment ratios
Measured: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 24
Effect of Olaparib on Exposure to Letrozole - Cmax ss
Letrozole Cmax ss in the presence and absence of co-administered olaparib, and associated Cmax ss treatment ratios
Measured: Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 38 and Day 43
Effect of Letrozole on Exposure to Olaparib - Cmax ss
Olaparib Cmax ss in the presence and absence of co-administered letrozole, and associated Cmax ss treatment ratios
Measured: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 43
Effect of Olaparib on Exposure to Tamoxifen - AUC0-τ
Tamoxifen, N-DMT and endoxifen AUC0-τ, in the presence and absence of co-administered olaparib, and associated AUC0-τ treatment ratios
Measured: Pre-dose and at 1, 2, 4, 5, 6, 8, 12 and 24 hours post-dose on Day 26 and Day 31
Effect of Tamoxifen on Exposure to Olaparib - AUC0-τ
Olaparib AUC0-τ, in the presence and absence of co-administered tamoxifen, and associated AUC0-τ treatment ratios
Measured: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 31
Effect of Olaparib on Exposure to Anastrozole - AUC0-τ
Anastrozole Area under plasma concentration-time curve over the dosing interval at steady state (AUC0-τ), in the presence and absence of co-administered olaparib, and associated AUC0-τ treatment ratios
Measured: Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 19 and Day 24
Effect of Anastrozole on Exposure to Olaparib - AUC0-τ
Olaparib AUC0-τ, in the presence and absence of co-administered anastrozole, and associated AUC0-τ treatment ratios
Measured: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 24
Effect of Olaparib on Exposure to Letrozole - AUC0-τ
Letrozole AUC0-τ, in the presence and absence of co-administered olaparib, and associated AUC0-τ treatment ratios
Measured: Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 38 and Day 43
Effect of Letrozole on Exposure to Olaparib - AUC0-τ
Olaparib AUC0-τ, in the presence and absence of co-administered letrozole, and associated AUC0-τ treatment ratios
Measured: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 43

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Sep 201429 Apr 2019

First posted21 Mar 2014 (estimated)
Study start1 Sep 2014
Primary completion30 Apr 2015
Study completion29 Apr 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Solid TumoursStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 79 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02093351
Sponsor's protocol ID: D081CC00001
Status last verified: Sep 2019
First submitted: 6 Mar 2014
Last updated: 2 Oct 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Plummer R, Verheul HM, De Vos FYFL, Leunen K, Molife LR, Rolfo C, Grundtvig-Sorensen P, De Greve J, Rottey S, Jerusalem G, Italiano A, Spicer J, Dirix L, Goessl C, Birkett J, Spencer S, Learoyd M, Bailey C, Dean E. Pharmacokinetic Effects and Safety of Olaparib Administered with Endocrine Therapy: A Phase I Study in Patients with Advanced Solid Tumours. Adv Ther. 2018 Nov;35(11):1945-1964. doi: 10.1007/s12325-018-0804-z. Epub 2018 Oct 15.
PubMed 30324586

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm

All Solid Tumours trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label, Non-randomised, Parallel Group, Multicentre, Phase I Study to Assess the Safety and Effect of Olaparib at Steady State on the Pharmacokinetics of the Anti-hormonal Agents Anastrozole, Letrozole and Tamoxifen at Steady State, and the Effect of the Anti-hormonal Agents on Olaparib, Following Administration in Patients With Advanced Solid Cancer
ClinicalTrials.gov ID: NCT02093351
Acronym / sponsor ID: D081CC00001
Conditions: Solid Tumours
Keywords: oncology, cancer, tumour, neoplasm, anticancer drug, pharmacokinetics, olaparib, anastrozole, tamoxifen, letrozole,
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 79 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: 1 Sep 2014 (actual)
Primary completion: 30 Apr 2015 (actual)
Study completion: 29 Apr 2019 (actual)
First posted: 21 Mar 2014 (estimated)
Results: Posted 1 Jun 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Cohort 1 - Tamoxifen	Experimental	Drug: Olaparib, Drug: Tamoxifen, Procedure: Pharmacokinetic samplingOlaparib-alone Steady state PK, Tamoxifen-alone steady state PK, Combined olaparib and Tamoxifen steady state PK.
Cohort 2 - Anastrozole	Experimental	Drug: Olaparib, Drug: Anastrozole, Procedure: Pharmacokinetic samplingOlaparib-alone Steady state PK, Anastrozole-alone steady state PK, Combined olaparib and Anastrozole steady state PK.
Cohort 3 - Letrozole	Experimental	Drug: Olaparib, Drug: Letrozole, Procedure: Pharmacokinetic samplingOlaparib-alone Steady state PK, Letrozole-alone steady state PK, Combined olaparib and Letrozole steady state PK.

Who may qualify

Ages: 18 to 130 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (24 listed)

Provision of written informed consent prior to any study specific procedures
Male or female aged ≥18 years
Histological or cytological confirmation of any malignant solid tumour in an advanced or metastatic setting who meet one of the criteria below:
Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

Key exclusion criteria (17 listed)

Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff, its agents, and/or staff at the study site)
Previous enrolment in the present study
Exposure to an investigational product (IP) (including PARP inhibitor) within 30 days or 5 half lives (whichever is the longer) prior to enrolment
Prior chemotherapy within 3 weeks of study entry
Prior radiotherapy within 2 weeks of study entry

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Olaparib2 x 150mg tablets, twice daily Day 1-5, and Day 27 onwards (Cohort 1), Day 20 onwards (Cohort 2) or Day 39 onwards (Cohort 3)	Drug	Cohort 1 - Tamoxifen, Cohort 2 - Anastrozole, Cohort 3 - Letrozole
Tamoxifen60mg Tamoxifen once daily, Day 10 - Day 13; 20mg Tamoxifen once daily, Day 14 - Day 31	Drug	Cohort 1 - Tamoxifen
Anastrozole1mg Anastrozole once daily Day 10 - Day 24	Drug	Cohort 2 - Anastrozole
Letrozole2.5mg Letrozole once daily Day 10 - Day 43	Drug	Cohort 3 - Letrozole
Pharmacokinetic samplingBlood sampling over 12-24 hour period for pharmacokinetic analysis	Procedure or surgery	Cohort 1 - Tamoxifen, Cohort 2 - Anastrozole, Cohort 3 - Letrozole

Primary outcome

Effect of Olaparib on Exposure to Tamoxifen - Cmax ss
Time frame: Pre-dose and at 1, 2, 4, 5, 6, 8, 12 and 24 hours post-dose on Day 26 and Day 31
Tamoxifen, N-desmethyl tamoxifen (N-DMT) and endoxifen Cmax ss in the presence and absence of co-administered olaparib, and associated Cmax ss treatment ratios
Effect of Tamoxifen on Exposure to Olaparib - Cmax ss
Time frame: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 31
Olaparib Cmax ss in the presence and absence of co-administered tamoxifen, and associated Cmax ss treatment ratios
Effect of Olaparib on Exposure to Anastrozole - Cmax ss
Time frame: Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 19 and Day 24
Anastrozole maximum plasma concentration at steady state (Cmax ss) in the presence and absence of co-administered olaparib, and associated Cmax ss treatment ratios
Effect of Anastrozole on Exposure to Olaparib - Cmax ss
Time frame: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 24
Olaparib Cmax ss in the presence and absence of co-administered anastrozole, and associated Cmax ss treatment ratios
Effect of Olaparib on Exposure to Letrozole - Cmax ss
Time frame: Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 38 and Day 43
Letrozole Cmax ss in the presence and absence of co-administered olaparib, and associated Cmax ss treatment ratios
Effect of Letrozole on Exposure to Olaparib - Cmax ss
Time frame: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 43
Olaparib Cmax ss in the presence and absence of co-administered letrozole, and associated Cmax ss treatment ratios
Effect of Olaparib on Exposure to Tamoxifen - AUC0-τ
Time frame: Pre-dose and at 1, 2, 4, 5, 6, 8, 12 and 24 hours post-dose on Day 26 and Day 31
Tamoxifen, N-DMT and endoxifen AUC0-τ, in the presence and absence of co-administered olaparib, and associated AUC0-τ treatment ratios
Effect of Tamoxifen on Exposure to Olaparib - AUC0-τ
Time frame: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 31
Olaparib AUC0-τ, in the presence and absence of co-administered tamoxifen, and associated AUC0-τ treatment ratios
Effect of Olaparib on Exposure to Anastrozole - AUC0-τ
Time frame: Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 19 and Day 24
Anastrozole Area under plasma concentration-time curve over the dosing interval at steady state (AUC0-τ), in the presence and absence of co-administered olaparib, and associated AUC0-τ treatment ratios
Effect of Anastrozole on Exposure to Olaparib - AUC0-τ
Time frame: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 24
Olaparib AUC0-τ, in the presence and absence of co-administered anastrozole, and associated AUC0-τ treatment ratios
Effect of Olaparib on Exposure to Letrozole - AUC0-τ
Time frame: Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 38 and Day 43
Letrozole AUC0-τ, in the presence and absence of co-administered olaparib, and associated AUC0-τ treatment ratios
Effect of Letrozole on Exposure to Olaparib - AUC0-τ
Time frame: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 43
Olaparib AUC0-τ, in the presence and absence of co-administered letrozole, and associated AUC0-τ treatment ratios

Results and safety

Results posted to the registry on 1 Jun 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1 - Tamoxifen	30	28
Cohort 2 - Anastrozole	23	21
Cohort 3 - Letrozole	26	23
Olaparib (Part B)	0	0

Primary outcome: Effect of Olaparib on Exposure to Tamoxifen - Cmax ss

Time frame: Pre-dose and at 1, 2, 4, 5, 6, 8, 12 and 24 hours post-dose on Day 26 and Day 31. Geometric mean (Geometric Coefficient of Variation). Unit: mcg/mL

Measure	Cohort 1 - Tamoxifen Alone (Treatment Period 2) n = 24	Cohort 1 - Olaparib + Tamoxifen (Treatment Period 3) n = 18
PK analysis of tamoxifen	130.3 (27.3)	154.2 (34.9)
PK analysis of N-DMT	162.9 (28.0)	149.1 (44.8)
PK analysis of endoxifen	5.923 (65.7)	5.727 (61.2)

Cohort 1 - Tamoxifen Alone (Treatment Period 2) vs Cohort 1 - Olaparib + Tamoxifen (Treatment Period 3): GLS Mean Ratio: 1.13 (90% CI 1.06 to 1.22)

Population analysed: The PK Analysis set included all patients who received a study drug dose and provided evaluable PK profiles for at least 1 treatment period in Part A.

Primary outcome: Effect of Tamoxifen on Exposure to Olaparib - Cmax ss

Time frame: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 31. Geometric mean (Geometric Coefficient of Variation). Unit: mcg/mL

Measure	Cohort 1 - Olaparib (Treatment Period 1) n = 27	Cohort 1 - Olaparib + Tamoxifen (Treatment Period 3) n = 19
Value	9.456 (41.5)	7.216 (43.6)

Cohort 1 - Olaparib (Treatment Period 1) vs Cohort 1 - Olaparib + Tamoxifen (Treatment Period 3): GLS Mean Ratio: 0.80 (90% CI 0.71 to 0.90)

Population analysed: The PK Analysis set included all patients who received a study drug dose and provided evaluable PK profiles for at least 1 treatment period in Part A.

Primary outcome: Effect of Olaparib on Exposure to Anastrozole - Cmax ss

Time frame: Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 19 and Day 24. Geometric mean (Geometric Coefficient of Variation). Unit: micrograms per millilitre (mcg/mL)

Measure	Cohort 2 - Anastrozole Alone (Treatment Period 2) n = 20	Cohort 2 - Olaparib + Anastrozole (Treatment Period 3) n = 19
Value	40.98 (36.2)	35.83 (31.9)

Cohort 2 - Anastrozole Alone (Treatment Period 2) vs Cohort 2 - Olaparib + Anastrozole (Treatment Period 3): Geometric Least Squares (GLS) Mean Ratio: 0.90 (90% CI 0.84 to 0.97)

Population analysed: PK Analysis set included all patients who received a study drug dose and provided evaluable PK profiles for at least 1 treatment period in Part A.

Primary outcome: Effect of Anastrozole on Exposure to Olaparib - Cmax ss

Time frame: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 24. Geometric mean (Geometric Coefficient of Variation). Unit: mcg/mL

Measure	Cohort 2 - Olaparib (Treatment Period 1) n = 22	Cohort 2 - Olaparib + Anastrozole (Treatment Period 3) n = 20
Value	9.490 (34.3)	8.256 (39.9)

Cohort 2 - Olaparib (Treatment Period 1) vs Cohort 2 - Olaparib + Anastrozole (Treatment Period 3): GLS Mean Ratio: 0.94 (90% CI 0.84 to 1.04)

Population analysed: PK Analysis set included all patients who received a study drug dose and provided evaluable PK profiles for at least 1 treatment period in Part A.

Adverse events

Time frame: For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1 - Tamoxifen	2 of 30 (6.7%)	27 of 30 (90%)	1 of 30
Cohort 2 - Anastrozole	0 of 23 (0%)	20 of 23 (87%)	1 of 23
Cohort 3 - Letrozole	0 of 26 (0%)	20 of 26 (76.9%)	1 of 26
Olaparib (Part B)	22 of 69 (31.9%)	66 of 69 (95.7%)	1 of 69

Limitations and caveats (from the sponsor): At the end of Part B, the continued access phase (CAP) allowed patients to continue to receive olaparib if deriving clinical benefit. No clinical data was databased during the CAP, thus AE data is presented to the end of Part B only.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30324586Plummer R, Verheul HM, De Vos FYFL, Leunen K, Molife LR, Rolfo C, Grundtvig-Sorensen P, De Greve J, Rottey S, Jerusalem G, Italiano A, Spicer J, Dirix L, Goessl C, Birkett J, Spencer S, Learoyd M, Bailey C, Dean E. Pharmacokinetic Effects and Safety of Olaparib Administered with Endocrine Therapy: A Phase I Study in Patients with Advanced Solid Tumours. Adv Ther. 2018 Nov;35(11):1945-1964. doi: 10.1007/s12325-018-0804-z. Epub 2018 Oct 15.
Clinical Study Protocol REDACTEDLink provided by the sponsor.

Related trials for Solid Tumours

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Tsveta Milenkova study director

AstraZeneca

Ruth Plummer principal investigator

Sir Bobby Robson Cancer Trials Research Centre

14 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Olaparib, Tamoxifen and Anastrozole in people with Solid Tumours, run by AstraZeneca at 14 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Belgium, United Kingdom, Netherlands, Denmark, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effect of Olaparib on Exposure to Tamoxifen - Cmax ss (time frame: Pre-dose and at 1, 2, 4, 5, 6, 8, 12 and 24 hours post-dose on Day 26 and Day 31). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02093351, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2019.