Phase 1 Completed N=79 Basic Science

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

Solid Tumors

Source: ClinicalTrials.gov NCT02093351 ↗

Enrolled (actual)

Serious AEs

16.2%

Results posted

Jun 2016

Primary outcomePrimary: Effect of Olaparib on Exposure to Tamoxifen - Cmax ss — 130.3; 154.2; 162.9; 149.1 mcg/mL

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 phase and will provide additional safety data.

Outcome Measures

Outcome	Result	p-value
PRIMARY Effect of Olaparib on Exposure to Tamoxifen - Cmax ss	130.3; 154.2; 162.9; 149.1; 5.923; 5.727	—
PRIMARY Effect of Tamoxifen on Exposure to Olaparib - Cmax ss	9.456; 7.216	—
PRIMARY Effect of Olaparib on Exposure to Anastrozole - Cmax ss	40.98; 35.83	—
PRIMARY Effect of Anastrozole on Exposure to Olaparib - Cmax ss	9.490; 8.256	—
PRIMARY Effect of Olaparib on Exposure to Letrozole - Cmax ss	118.9; 111.8	—
PRIMARY Effect of Letrozole on Exposure to Olaparib - Cmax ss	10.05; 10.48	—
PRIMARY Effect of Olaparib on Exposure to Tamoxifen - AUC0-τ	2233; 2751; 3189; 2955; 119.3; 115.8	—
PRIMARY Effect of Tamoxifen on Exposure to Olaparib - AUC0-τ	62.12; 42.27	—
PRIMARY Effect of Olaparib on Exposure to Anastrozole - AUC0-τ	696.8; 582.5	—
PRIMARY Effect of Anastrozole on Exposure to Olaparib - AUC0-τ	55.49; 44.33	—
PRIMARY Effect of Olaparib on Exposure to Letrozole - AUC0-τ	2292; 2167	—
PRIMARY Effect of Letrozole on Exposure to Olaparib - AUC0-τ	61.77; 67.82	—

Eligibility Criteria

Inclusion Criteria

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).
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 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.

Exclusion Criteria

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
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 h

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Data sourced from ClinicalTrials.gov (NCT02093351). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.