The Pharmacokinetics and Safety of Olaparib Alone and With Paclitaxel in Chinese Patients With Advanced Solid Tumour.
Condition: Advanced Solid Tumours
MeSH terms: Neoplasms
Intervention: Olaparib; Paclitaxel; Olaparib
Intervention description: Tablet-150mg, Oral; Injection; Tablet-100mg, Oral
Intervention MeSH terms: Paclitaxel; Olaparib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Chinese Patients

Summary:

      This is a 2 parts phase I, open label trial of olaparib monotherapy and olaparib in
      combination with paclitaxel in patients with solid tumours. Part A will assess the single and
      multiple dose pharmacokinetics of olaparib monotherapy and multiple dose pharmacokinetics of
      olaparib in combination with paclitaxel. Part B will assess the safety of multiple doses of
      olaparib in Cohort 1 and of olaparib when co-administered with paclitaxel in Cohort 2
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provision of fully informed consent

          2. Patient aged ≥ 18 years

          3. Histologically or, where appropriate, cytologically confirmed malignant solid tumour
             refractory or resistant to standard therapy and for which no suitable effective
             standard therapy exists

          4. life expectancy of ≥ 12 weeks

          5. Patients for Cohort 2 must be eligible for paclitaxel treatment

          6. Willing and able to comply with the protocol for the duration of the study including
             undergoing treatment and scheduled visits and examinations

          7. ECOG performance status ≤ 2

          8. Satisfactory organ and bone marrow function measured within 28 days prior to
             administration of study treatment including - Haemoglobin ≥ 10.0 g/dL and no blood
             transfusion in the 4 weeks prior to the first dosing of study drug. - Absolute
             neutrophil count ≥ 1.5 × 109/L

          9. 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.

         10. Patients must be on a stable concomitant medication regimen, defined as no changes in
             medication or in dose within 2 weeks prior to start of olaparib dosing, except for
             bisphosphonates, denosumab and corticosteroids, which should be stable for at least 4
             weeks prior to start of olaparib dosing.

        Exclusion criteria:

          1. Involvement in the planning and/or conduct of the study.

          2. Previous enrolment in the present study.

          3. Treatment with any investigational product during the last 14 days (or a longer period
             depending on the defined characteristics of the agents used).

          4. Any previous treatment with a Poly (ADP-ribose) polymerase (PARP) inhibitor, including
             olaparib.

          5. Patients with other malignancy within the last 5 years, except adequately treated
             non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, ductal
             carcinoma in situ, Stage 1, Grade 1 endometrial cancer, or other solid tumours
             including lymphomas (without bone marrow involvement) curatively treated with no
             evidence of disease for ≥5 years.

          6. Patients unable to swallow orally administered medication and patients with
             gastrointestinal disorders likely to interfere with absorption of the study
             medication. These include patients with gastric or intestinal cancer or patients with
             prior surgical procedures such as full or partial gastrectomy.

          7. Patients receiving any systemic chemotherapy, radiotherapy (except for palliative
             reasons), within 4 weeks from the last dose prior to study treatment.

          8. Concomitant use of known potent CYP3A4 (Cytochrome P450 3A4) inhibitors.

          9. Patients with any ongoing toxicities (>CTCAE (Common Terminology Criteria for Adverse
             Events) grade 2), with the exception of alopecia, caused by previous cancer therapy.

         10. Resting ECG with QTc (Heart Rate Corrected QT interval) > 470msec or family history of
             long QT syndrome.

         11. Patients with interstitial pneumonia or diffused symptomatic fibrosis of the lungs.

         12. Patients with myelodysplastic syndrome/acute myeloid leukaemia.

         13. Patients with symptomatic uncontrolled brain metastases.

         14. Major surgery within 2 weeks of starting study treatment and patients must have
             recovered from any effects of any major surgery.

         15. Patients considered a poor medical risk due to a serious, uncontrolled medical
             disorder, non-malignant systemic disease or active, uncontrolled infection.

         16. Immunocompromised patients, e.g. patients who are known to be serologically positive
             for human immunodeficiency virus (HIV).

         17. Patients with known active hepatic disease (i.e. Hepatitis B or C).

         18. Patients with a known hypersensitivity to olaparib, paclitaxel or any of the
             excipients of the product.

         19. Breastfeeding women.

         20. Clinical judgement by the investigator that the patient should not participate in the
             study.