Olaparib in gBRCA Mutated Pancreatic Cancer whose Disease Has Not Progressed on First Line Platinum-Based Chemotherapy

• Register: EUCTR
• Last refreshed on: 24 November 2014
• Main ID: EUCTR2014-001589-85-ES
• Date of registration: 03/10/2014
• Prospective Registration: Yes
• Primary sponsor: Astrazeneca AB
• Public title: Olaparib in gBRCA Mutated Pancreatic Cancer whose Disease Has Not Progressed on First Line Platinum-Based Chemotherapy
• Scientific title: A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Maintenance Olaparib Monotherapy in Patients with gBRCA Mutated Metastatic Pancreatic Cancer whose Disease Has Not Progressed on First Line Platinum Based Chemotherapy - POLO
• Date of first enrolment: 19/11/2014
• Target sample size: 145
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001589-85
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Australia, Belgium, Canada, France, Germany, Israel, Korea, Republic of, Netherlands, Spain, United Kingdom, United States

Contacts

• Name: Information center
• Affiliation: AstraZeneca

• Name: Information center
• Affiliation: AstraZeneca

Key inclusion & exclusion criteria

Inclusion criteria:
For inclusion in the study patients should fulfil the following criteria:
1. Provision of informed consent prior to any study specific procedures
2. Patients must be male or female >o=18 years of age
3. Histologically or cytologically confirmed pancreas adenocarcinoma receiving initial chemotherapy for metastatic disease and without evidence of disease progression on treatment
4. Patients with measurable disease and/or non-measurable or no evidence of disease assessed at baseline by CT (or MRI where CT is contraindicated) will be entered in this study.
5. Documented mutation in gBRCA1 or gBRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function)
6. Patients are on treatment with a first line platinum-based regimen for metastatic pancreas cancer, have received a minimum of 16 weeks of continuous platinum treatment and have no evidence of progression based on investigator?s opinion.
7. Patients who have received platinum as potentially curative treatment for a prior cancer (eg ovarian cancer) or as adjuvant/neoadjuvant treatment for pancreas cancer are eligible provided at least 12 months have elapsed between the last dose of platinum-based treatment and initiation of the platinum-based chemotherapy for metastatic pancreas cancer.
8. Patients must have normal organ and bone marrow function measured within 4 weeks prior to administration of study treatment as defined below:
? Haemoglobin >o= 9.0 g/dL with no blood transfusions (packed red blood cells and platelet transfusions) in the past 28 days
? Absolute neutrophil count (ANC) >o= 1.5 x 109/L
? White blood cells (WBC) >3 x 109/L
? No features suggestive of MDS/AML on peripheral blood smear
? Platelet count >o= 100 x 109/L
? Total bilirubin ? AST (SGOT)/ALT (SGPT) ? Serum creatinine 9. ECOG performance status 0-1 at date signing of informed consent
10. Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test. Postmenopausal is defined as:
? Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
? Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in
the post menopausal range for women under 50
? Radiation-induced oophorectomy with last menses >1 year ago
? Chemotherapy-induced menopause with >1 year interval since last menses
? Surgical sterilisation (bilateral oophorectomy or hysterectomy)
11. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
12. Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary tumour or a metastatic site if available or 3 unstained cytology slides if available.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 75

Exclusion criteria:
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1. Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff and/or staff at the study site).
2. gBRCA1 and/or gBRCA2 mutations that are considered to be non detrimental (eg, ?Variants of uncertain clinical significance? or ?Variant of unknown significance? or ?Variant, favour polymorphism? or ?benign polymorphism? etc.).
3. Progression of tumour between start of first line platinum based chemotherapy for metastatic pancreas cancer and randomisation.
4. Cytotoxic chemotherapy or non-hormonal targeted therapy within 28 days of Cycle 1 Day 1 is not permitted. Palliative radiotherapy must have been completed 14 or more days before Cycle 1 Day 1. The patient can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study as long as these were started at least 2 weeks prior to study treatment.
5. Previous randomisation in the present study.
6. Exposure to an investigational product within 30 days or 5 half lives (whichever is longer) prior to randomisation
7. Any previous treatment with a PARP inhibitor, including Olaparib.
8. Patients with second primary cancer, EXCEPTIONS: adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix, Ductal Carcinoma in Situ (DCIS), stage 1 grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for >o= 5 years prior to study entry.
9. 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.
10. Concomitant use of known potent CYP3A4/5 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
11. Persistent toxicities (?CTCAE grade 2) caused by previous cancer therapy, excluding alopecia and CTCAE grade 3 peripheral neuropathy.
12. Patients with myelodysplastic syndrome/acute myeloid leukaemia.
13. Major surgery within 2 weeks of starting study treatment: patients must have recovered from any effects of any major surgery.
14. Immunocompromised patients, eg, patients who are known to be serologically positive for human immunodeficiency virus (HIV).
15. Clinically significant uncontrolled medical conditions are not permitted (eg active infection requiring IV antibiotics, symptomatic congestive heart failure, unstable angina pectoris, recent (3 months) myocardial infarction, extensive bilateral interstitial lung disease, psychiatric illness that would limit ability to comply with study procedures, and any other medical condition that, in the opinion of the investigator, places the patient at unacceptable risk of toxicity. NB: Diabetes which is controlled by medication does not exclude participation in the study
16. Patients with a history of treated CNS metastases are eligible, provided they meet all of the following criteria: Disease outside the CNS is present. No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study. No history of intracranial haemorrhage or spinal cord haemorrhage. Minimum of 2 weeks between completion of radiotherapy and cycle 1 Day 1 and recovery from significant (Grade >o=3) acute toxicity wi

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with gBRCA mutated metastatic pancreatic cancer whose disease has not progressed on first line platinum based chemotherapy

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: olaparib
Product Code: AZD2281
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: olaparib
CAS Number: 763113-22-0
Other descriptive name: OLAPARIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: olaparib
Product Code: AZD2281
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: olaparib
CAS Number: 763113-22-0
Other descriptive name: OLAPARIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To determine the efficacy of Olaparib maintenance monotherapy compared to placebo by progression free survival (PFS)

Timepoint(s) of evaluation of this end point: - Interim PFS analyses (~ 45 PFS events): PFS
- Final PFS (~ 89 PFS events): PFS, PFS2, TDT, TFST, TSST, OS, time to deterioration of Global QoL and PAN-26 pain scale Efficacy Data
- Final OS analyses (~ 106 OS events): PFS2, TFST, TSST, OS, time to deterioration of Global QoL and PAN-26 pain scale

Primary end point(s): Determine the efficacy of Olaparib maintenance monotherapy compared to placebo by progression free survival (PFS)-Progression Free Survival (PFS) by BICR using modified RECIST 1.1

Secondary Objective: ? To determine the efficacy of Olaparib maintenance monotherapy compared to placebo
? To assess the effect of Olaparib on the Health-related Quality of Life (HRQoL) as measured by EORTC QLQ-C30 global QoL scale.

Secondary Outcome(s)

Secondary end point(s): ? To determine the efficacy of Olaparib maintenance monotherapy compared to placebo
? To assess the effect of Olaparib on the Health-related Quality of Life (HRQoL) as measured by EORTC QLQ-C30 global QoL scale

Timepoint(s) of evaluation of this end point: - Overall Survival (observed and predicted using observed PFS and OS data), Time from randomisation to second progression (PFS2), Time from randomisation to first subsequent therapy or death (TFST), Time from randomisation to second subsequent therapy or death (TSST), Time from randomisation to study treatment discontinuation or death (TDT), Objective Response Rate by BICR using modified RECIST 1.1 criteria for evaluable patients, Disease Control Rate at 16 weeks by BICR using modified RECIST 1.1 criteria
- Adjusted mean change from baseline in global QoL score from the EORTC-QLQC30 questionnaire

Secondary ID(s)

D081FC00001

Source(s) of Monetary Support

Astrazeneca AB