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A Randomised Phase II Trial of Olaparib Maintenance Versus Placebo Monotherapy in Patients With Chemosensitive Advanced Non-Small Cell Lung Cancer

Phase 2
18 Years
Not Enrolling
Non-small Cell Lung Cancer

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Trial Information

A Randomised Phase II Trial of Olaparib Maintenance Versus Placebo Monotherapy in Patients With Chemosensitive Advanced Non-Small Cell Lung Cancer

This is a multicentre randomised phase II trial. Patients are initially registered either
before or during 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 or placebo until disease progression. They will be
monitored by CT scan every two cycles until disease progression, where 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.

All randomised patients for whom we have a baseline translational blood sample will be asked
to provide a follow up blood sample upon randomisation and again at radiological
progression. Registered patients with progressive disease after the initial induction
chemotherapy will be asked to provide a follow-up blood sample at the end of induction

Inclusion Criteria

Inclusion Criteria - Registration:

- Histological diagnosis of NSCLC. Histology can be either squamous or non-squamous.

- Stage IIIB or stage IV lung cancer that is not amenable to curative therapy.

- ECOG performance status 0-1.

- Have had no prior systemic treatment for lung cancer including previous adjuvant
and neoadjuvant therapy. Patients who have already started their chemotherapy are not

- Eligible to receive standard platinum doublet-based chemotherapy.

- Men or women, aged 18 or over and capable of giving informed consent.

- Willing to consent to provide tissue and blood for translational research.

- Informed consent prior to any study specific procedures.

Exclusion Criteria - Registration:

- Evidence of small cell, large cell neuroendocrine or carcinoid histology.

- Have a serious or uncontrolled medical condition that could compromise the patients'
ability to adhere to the protocol.

- Have a secondary malignancy (except adequately treated non-melanomatous skin cancer,
or other cancer considered cured by surgical resection or radiation). Patients who
have had another malignancy in the past but have been disease free for more than 5
years are eligible.

- Have had a blood transfusion within 4 weeks prior to study entry, and have a white
blood count >3x109/L.

- Have central nervous system metastases (unless the patient has completed successful
local therapy for central nervous system metastases).

- Are receiving concurrent administration of any other systemic antitumour therapy.

- Have received a recent (within 30 days of enrolment) or are receiving concurrent
yellow fever vaccination.

- Previous treatment with PARP inhibitors.

- Difficulty swallowing.

- 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.

- Patients with myelodysplastic syndrome / acute myeloid leukaemia.

- Congenital long QT syndrome.

Inclusion Criteria - Randomisation:

- Partial or complete response to platinum containing doublet chemotherapy after a
minimum of 3 cycles, according to RECIST, as assessed by the local radiologist.
Patients with stable disease or a mixed response following induction chemotherapy
should not be included.

- Adequate organ function, including the following:

1. Adequate bone marrow reserve; absolute neutrophil count (ANC) >1.5 x 109/L,
platelets >100 x 109/L, Haemoglobin of >10g/dl.

2. Hepatic: total bilirubin <1.5 times the upper limit of normal (xULN); alkaline
phosphate (ALP), aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) <2.5 x ULN. ALP, AST and ALT <5 x ULN is acceptable if the liver has
tumour involvement.

3. Renal: calculated creatinine clearance (CrCl) >50ml/min based on the original
weight based Cockroft and Gault or Wright formula, serum creatinine <1.5 x
institutional ULN.

4. No features suggestive of myelodysplastic syndrome/acute myeloid leukaemia on
peripheral blood smear.

- Willing to use two adequate forms of contraception throughout the trial and for three
months following last administration of olaparib.

- Informed consent.

Exclusion Criteria - Randomisation:

- Patients with radiological disease progression or stable disease.

- Have received treatment with an agent that has not received regulatory approval,
within 30 days of study entry.

- Have had a blood transfusion in the period between induction chemotherapy and
starting Olaparib dosing and have a WBC >3 x109/L.

- Resting ECG with measurable QTc >/- 480 msec.

- Are pregnant or breastfeeding.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Outcome Description:

To establish the anti-tumour activity of Olaparib (measured by progression free survival),we will document the time from randomisation to any disease progression and/or death, defined according to strict RECIST (Response Evaluation Criteria in Solid Tumours) v1.1. Lesions will be compared to baseline measurements to assess progression.

Outcome Time Frame:

72 weeks

Safety Issue:


Principal Investigator

Dean Fennell, Professor

Investigator Role:

Study Chair

Investigator Affiliation:

University of Leicester


United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

May 2013

Completion Date:

Related Keywords:

  • Non-Small Cell Lung Cancer
  • non-small cell
  • lung cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms