A multi-arm non-comparative platform trial of new second-line treatments for metastatic pancreatic cancer patients based on a patient's individual biomarkers
- Conditions
- CancerMalignant neoplasm of pancreas
- Registration Number
- ISRCTN16004234
- Lead Sponsor
- HS Greater Glasgow and Clyde
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Stopped
- Sex
- All
- Target Recruitment
- 40
Core Inclusion Criteria:
1. Patient has been enrolled in the Precision- Panc- Master Protocol and their tissue taken post first line treatment has been deemed suitable for NGS analysis
2. Patient has provided signed informed consent for the appropriate PRIMUS-004 Appendix prior to any trial procedures being carried out
3. Age = 16 years
4. Histologically confirmed metastatic pancreatic ductal adenocarcinoma and its variants
5. Measurable disease as per Response Evaluation Criteria in Solid Tumours (RECIST) V1.1
6. Adequate organ and bone marrow function as defined below (also refer to adequate organ function as defined in relevant drug-specific appendix):
6.1. Absolute neutrophil count = 1.5 x109/L
6.2. Platelet count = 100 x109/L
6.3. Total bilirubin = 1.5 x ULN, unless the patient has documented Gilbert’s syndrome
6.4. AST and/or ALT = 2.5 x ULN, or = 5 x ULN if the patient has liver metastases
6.5. GFR = 51 ml/min as assessed using the Cockroft Gault equation, or Wright formula or measured by EDTA clearance
7. Negative serum or urine HCG test for females with child-bearing potential. Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential
8. Woman of child-bearing potential, and men with female partners of child bearing potential, must agree to use adequate contraceptive measures (see specific appendixsection 4.1.8.1) for the duration of the study and for up to 6 months after the completion of study treatment. Men with pregnant or lactating partners should be advised to use barrier method contraception to prevent exposure to the foetus or neonate
9. Compliant, and can be followed up regularly
Appendix Specific Inclusion Criteria
1. Patient has the ability to provide written informed consent to participate in the trial and be compliant with the protocol requirements
2. Patient must have measurable disease (pre- and post-platinum chemotherapy) as per RECIST V1.1
3. ECOG Performance status 0-1
4. Life expectancy of at least 12 16 weeks
5. Haemoglobin = 10.0 g/dL, with no blood transfusion in the past 28 days
6. Patient must have completed at least 16 weeks of platinum chemotherapy as first-line treatment for advanced pancreatic cancer
7. Patients must have achieved at least stable disease as a response to platinum .by RECIST V1.1 and this must be confirmed by repeat assessment at a minimum of 4 weeks from previous scan
8. Archival tissue sample taken prior to platinum chemotherapy is available and suitable for Next Generation Sequencing analysis
9. Ability to swallow study medication and no gastrointestinal disorders likely to cause malabsorption of study drug(s).
10. Known HRRm status from pre-first line treatment biopsy
Core Exclusion Criteria
1. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period (no longer receiving experimental treatment) of an interventional study unless that study primary endpoint has been met
2. Patients weighing less than 30 kg:
3. Receipt of last dose of anti-cancer therapy (chemotherapy, targeted therapy, immunotherapy, etc.) within 21 days of Cycle 1 Day 1. A duration of five half lives is allowed for patients treated with non-cytotoxic drugs. If sufficient wash-out time has not occurred within 21 days due to the schedule or pharmacokinetics properties of an agent, a longer washout period will be required as agreed by the Investigator.
4. Palliative radiotherapy must have been completed 21 or more days before Cycle 1 Day 1. The patient can receive a stable dose of bisphosphonates or denosumab for bone metastases, if appropriate, before and during the study as long as these were started at least 5 days prior to the study treatment
5. Major surgery (as defined by the investigator) within 2 weeks of starting study treatment: patients must have recovered from any effects of any major surgery
6. Any other malignancy which has been active or treated within the past three years, with the exception of cervical intraepithelial neoplasia, non-melanoma skin cancer, ductal carcinoma in situ, stage 1 grade 1 endometrial carcinoma, or other solid tumours curatively treated with no evidence of disease for = 3 years prior to study entry
7. With the exception of alopecia and Common Terminology Criteria for Adverse Events (CTCAE) grade 2 neuropathy, any unresolved toxicities from prior therapy = grade 2
8. History of myocardial ischemia (MI), unstable angina, stroke, or transient ischemia within previous 6 months
9. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases that places the patient at unacceptable risk of toxicity or non-compliance.
10. Patients with symptomatic uncontrolled brain metastases. Patients with a history of treated central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria: disease outside the CNS is present, no clinical evidence of progression since completion of CNS-directed therapy, minimum 3 weeks between completion of radiotherapy and Cycle 1 Day 1 and recovery from significant (Grade = 3) acute toxicity with no ongoing requirement for >10 mg of prednisolone per day or an equivalent dose of other corticosteroid. If on corticosteroids, the patient should be receiving a stable dose of corticosteroids, started at least 4 weeks prior to treatment
11. Women who are breast feeding
Appendix I Specific Exclusion Criteria:
12. Previous treatment with a PARP inhibitor (including olaparib) or other ATR inhibitor (unless treatment was for less than 3 weeks duration and at least 12 months have elapsed between the last dose and randomisation.
13. Patients with myelodysplastic syndrome (MDS)/Acute myeloid leukaemia (AML) or with features suggestive of MDS/AML.
14. Mean resting corrected QT interval (QTc) >470 msec for females and >450 for men, obtained from 3 electrocardiograms (ECGs).
15. Patients at risk of brain perfusion problems
16. Patients with relative hypotension(<90/60 mm Hg) or clinically relevant orthostatic hypotension, including a fall in
systolic blood pressure of > 20 mm Hg
17. A known hypersensitivity to olaparib, AZD6738 or any excipient of the
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) based on RECIST V1.1 at baseline, 8 weekly from randomisation until disease progression
- Secondary Outcome Measures
Name Time Method 1. Progression free survival (PFS) and overall survival (OS) based on RECIST V1.1 at baseline, 8 weekly from randomisation until disease progression<br>2. Safety profile based on CTCAE V5.0 at day 1 of each cycle (every 4 weeks)<br>3. Analysis of tumour and blood samples to determine the molecular profile and hypothesised biomarkers of therapeutic responsiveness with correlation to ORR, PFS & OS at baseline, 2 months after registration and on progression