Parp Inhibitor in advanced Non-small cell lung cancer
| ISRCTN | ISRCTN42518913 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN42518913 |
| EudraCT/CTIS number | 2012-003383-51 |
| ClinicalTrials.gov number | NCT01788332 |
| Secondary identifying numbers | 15521 |
- Submission date
- 08/11/2013
- Registration date
- 08/11/2013
- Last edited
- 26/05/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Mrs Sarah Bridges
Scientific
Scientific
6th Floor, Neuadd Meirionnydd
Heath Park
Cardiff
CF14 4YS
United Kingdom
| BridgesSE@cardiff.ac.uk |
Study information
| Study design | Multicentre double blind randomised phase II trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | A randomised phase II trial of Olaparib maintenance versus placebo monotherapy in patients with chemosensitive advanced non-small cell lung cancer |
| Study acronym | PIN |
| Study objectives | The purpose of this trial is to find out whether giving a drug called olaparib following chemotherapy will benefit patients with NSCLC who have responded to initial chemotherapy treatment by prolonging the time before the tumour re-grows. 114 patients who have responded to chemotherapy will be randomly allocated to receive either olaparib or placebo tablet by mouth. The rationale for this clinical trial is that chemotherapy damages tumour cell DNA and that NSCLC tumours that respond to chemotherapy are less able to repair this damage. This can be exploited by using olaparib, a drug which blocks an enzyme called PARP which is essential for DNA repair. This will prevent DNA repair and cause cancer cell death by a mechanism known as synthetic lethality. Synthetic lethality arises when a combination of mutations in two or more genes leads to cell death. If this study shows that olaparib does delay disease progression, a larger more detailed clinical trial will be needed to find out whether using olaparib actually makes patients live longer. |
| Ethics approval(s) | 13/WA/0117; First MREC approval date 07/06/2013 |
| Health condition(s) or problem(s) studied | Topic: National Cancer Research Network; Subtopic: Lung Cancer; Disease: Lung (non-small cell) |
| Intervention | Patients are initially registered before induction chemotherapy, their response to which will be used to determine whether they are eligible for randomisation. All patients will be asked to consent to archival tissue collection for translational analysis and to provide a translational blood sample. The second consent will precede randomisation to one of two groups of maintenance therapy (Olaparib or placebo) with 1:1 randomisation if they have had an objectively measured complete or partial response following standard chemotherapy. Randomised patients will receive Olaparib (300mg, two 150mg tablets, to be taken twice a day) or placebo until disease progression. They will be monitored by CT scan every two cycles until disease progression, when they will be managed according to local practice. Follow up will be for a maximum of 12 months from the point of randomisation or until disease progression. |
| Intervention type | Other |
| Primary outcome measure | Progression free survival (PFS); Timepoint(s): Will be analysed after 98 PFS events |
| Secondary outcome measures | 1. Change in tumour volume reduction; Timepoint(s): From randomisation to 6 weeks 2. Objective response rate; Timepoint(s): As assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 3. Overall survival; Timepoint(s): Time from randomisation to death with those still alive censored at date last seen 4. Safety, tolerability and feasibility of use; Timepoint(s): Will be assessed in real time |
| Overall study start date | 01/12/2013 |
| Completion date | 01/12/2014 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 114; UK Sample Size: 114 |
| Total final enrolment | 70 |
| Key inclusion criteria | At registration: 1. Histological diagnosis of NSCLC. Histology can be either squamous or nonsquamous. The same block or 10 unstained slides must be available for translational research. 2. Stage IIIB or stage IV lung cancer, that is not amenable to curative therapy 3. Eastern Cooperative Oncology Group (ECOG) performance status 01 4. Have had no prior systemic treatment for lung cancer including previous adjuvant and neoadjuvant therapy. Patients who have already started their induction chemotherapy are not eligible. 5. Eligible to receive standard platinum doublet-based chemotherapy 6. Men or women, aged 18 or over and capable of giving informed consent 7. Willing to consent to provide tissue and blood for translational research 8. Informed consent prior to any study procedures. At randomisation: 1. Partial or complete response to platinum containing doublet chemotherapy after a minimum of 3 cycles, as assessed by the local radiologist 2. Adequate organ function, including the following: 2.1. Adequate bone marrow reserve: absolute neutrophil count (ANC) = 1.5 x 10^9/L, platelets = 100 x 10^9/L , Haemoglobin of = 10g/dL 2.2. Hepatic: total bilirubin = 1.5 times the upper limit of normal (x ULN); alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) = 2.5 x ULN. ALP, AST, and ALT = 5 x times ULN is acceptable if the liver has tumour involvement 2.3. Renal: calculated creatinine clearance (CrCl) = 50mL/min based on the original weight based Crockcroft and Gault formula, Serum creatinine = 1.5 x institutional upper limit of normal (ULN) 2.4. If blood count suggestive of MDS/AML, no features suggestive of MDS/AML on peripheral blood smear 3. Patients with reproductive potential must be prepared to use adequate contraception throughout the study and for three months after the last dose of Olaparib 4. Informed consent prior to any study specific procedures Target Gender: Male & Female |
| Key exclusion criteria | At registration: 1. Evidence of small cell, large cell neuroendocrine or carcinoid histology 2. Have a serious or uncontrolled medical condition that in the opinion of the investigator would compromise the patients ability to adhere to the protocol 3. Have a secondary malignancy (except adequately treated non-melanomatous skin cancer, or other cancer that is considered cured by surgical resection or radiation). Patients who had another malignancy in the past but have been disease free for more than 5 years, are eligible. 4. Have had a blood transfusion within 4 weeks prior to entry and have a WBC >3 x 10^9/L 5. Have central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases eg. Involving complete surgical removal or radical radiotherapy to a solitary CNS metastasis ) 6. Are receiving concurrent administration of any other systemic antitumour therapy 7. Have received a recent (within 30 days of enrolment) or are receiving a concurrent yellow fever vaccination 8. Previous treatment with PARP inhibitors 9. Difficulty swallowing 10. Uncontrolled GI disorders such as active diverticulitis or colitis, or any major GI resection which could have an impact on patients' ability to absorb Olaparib 11. Patients with myelodysplastic syndrome/Acute myeloid leukaemia 12. Congenital long QT syndrome At randomisation: 1. Patients with radiological disease progression or stable disease 2. Have received treatment with an agent that has not received regulatory approval, within 30 days of study entry 3. Have had a blood transfusion within 4 weeks prior to entry and have a WBC >3 x 10^9/L 4. Resting ECG with QTc>/480 msec 5. Are pregnant or breastfeeding |
| Date of first enrolment | 01/12/2013 |
| Date of final enrolment | 01/12/2014 |
Locations
Countries of recruitment
- United Kingdom
- Wales
Study participating centre
6th Floor, Neuadd Meirionnydd
Cardiff
CF14 4YS
United Kingdom
CF14 4YS
United Kingdom
Sponsor information
Velindre NHS Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
Velindre Hospital
Velindre Road
Cardiff
CF14 2TL
Wales
United Kingdom
"ROR" |
https://ror.org/05ntqkc30 |
|---|
Funders
Funder type
Industry
AstraZeneca Limited (UK)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Plain English results | No | Yes | |||
| Basic results | 28/05/2020 | No | No | ||
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
26/05/2021: Cancer Research UK lay results summary link added to Results (plain English).
28/05/2020: The following changes were made to the trial record:
1. Added clinicaltrialsregister.eu link to basic results (scientific).
2. The total final enrollment was added.
13/08/2019: ClinicalTrials.gov number added.
16/02/2017: No publications found in PubMed, verifying study status with principal investigator.
