A PHASE III, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTI-CENTRE,INTERNATIONAL STUDY OF MEDI4736 AS SEQUENTIAL THERAPY IN PATIENTS WITHLOCALLY ADVANCED, UNRESECTABLE NON-SMALL CELL LUNG CANCER (STAGE III)WHO HAVE NOT PROGRESSED FOLLOWING DEFINITIVE, PLATINUM-BASED,CONCURRENT CHEMORADIATION THERAPY (PACIFIC)
- Conditions
- C34-C34 Malignant neoplasm of bronchus and lungMalignant neoplasm of bronchus and lung
- Registration Number
- PER-054-14
- Lead Sponsor
- AstraZeneca AB,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 3
For inclusion in the study patients should fulfil the following criteria:
1. Provision of signed, written and dated informed consent prior to any study specific procedures
2. Male or female aged 18 years or older
3. Patients must have histologically- or cytologically-documented NSCLC who present with locally advanced, unresectable (Stage III) disease (according to Version 7 of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology [IASLC Staging Manual in Thoracic Oncology]), OR
4. Patients must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy, which must be completed within 5 to 10 days prior to randomisation in the study. For patients who are recovering from toxicities associated with prior treatment, randomisation may be delayed by up to 14 days from the end of the chemoradiation therapy. The platinum-based chemotherapy regimen may contain one of the following agents: etoposide, vinblastine, a taxane (paclitaxel), or pemetrexed, according to the local standard of care regimens.
Patients must have received a total dose of radiation of at least 60 Gy to be randomised, as part of the chemoradiation therapy.
5. Patients must have not progressed following definitive, platinum-based, concurrent chemoradiation therapy.
6. Tumour sample requirements:
• Mandatory provision of an unstained, archived tumour tissue sample in a quantity sufficient to allow for analysis. Please refer to the Laboratory Manual for detail.
• A recent tumour biopsy (taken following completion of the most recent therapy) is an optional requirement, provided that a biopsy procedure is technically feasible and the procedure is not associated with unacceptable clinical risk.
7. Life expectancy ≥12 weeks
8. World Health Organization (WHO) Performance Status of 0 or 1
9. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered postmenopausal if they are amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
• Women <50 years old would be considered postmenopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution
• Women ≥50 years of age would be considered postmenopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, radiation-induced oophorectomy with last menses >1 year ago, chemotherapy-induced menopause with >1 year interval since last menses, or surgical sterilisation (bilateral oophorectomy or hysterectomy).
10. Adequate organ and marrow function as defined below:
• Absolute neutrophil count >1.5 x 109/L (1500 per mm3)
• Platelets >100 x 109/L (100,000 per mm3)
• Haemoglobin ≥9.0 g/dL (5.59 mmol/L)
• Serum creatinine CL >50 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976):
Males:
Creatinine CL= Weight (kg) x (140 – Age)
(mL/min) 72 x serum creatinine (mg/dL)
Females:
Creatinine CL = Weight (kg) x (140 – Age) x 0.85
(mL/min) 72 x serum creatinine (mg/dL)
• Serum bilirubin ≤1.5 x upper limit of normal (ULN). This will not apply to pati
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 both AstraZeneca/MedImmune staff and/or staff at the study site)
2. Previous enrolment or randomisation in the present study
3. Participation in another clinical study with an investigational product during the last 4 weeks
4. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
5. Mixed small cell and non-small cell lung cancer histology Patients who receive sequential chemoradiation therapy for locally advanced
NSCLC
7. Patients with locally advanced NSCLC who have progressed whilst definitive platinum based, concurrent chemoradiation therapy
8. Receipt of any immunotherapy, or investigational drug within 4 weeks prior to the first dose of study drug; and in the case of monoclonal antibodies 6 weeks prior to the first dose of study drug
9. Current or prior use of immunosuppressive medication within 28 days before the first dose of study drug, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Systemic steroid administration required to manage toxicities arising from radiation therapy delivered as part of the chemoradiation therapy for locally advanced NSCLC is allowed.
10. Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
11. Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy.
Patients with irreversible toxicity that is not reasonably expected to be exacerbated by study drug may be included (eg, hearing loss) after consultation with the AstraZeneca/MedImmune medical monitor.
12. Patients with any grade pneumonitis from prior chemoradiation therapy
13. Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1
14. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. NOTE: Local treatment of isolated lesions, excluding target lesions, for palliative intent is acceptable (eg, by local surgery or radiotherapy).
15. Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of study drug
16. Active or prior documented autoimmune disease within the past 2 years.
NOTE: Patients with vitiligo, Grave’s disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
17. Active or prior documented inflammatory bowel disease (eg, Crohn’s disease, ulcerative colitis)
18. History of primary immunodeficiency
19. History of organ transplant that requires therapeutic immunosuppression
History of hypersensitivity to MEDI4736 or any excipient
21. History of leptomeningeal carcinomatosis
22. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from
3 electrocardiograms (ECGs) using Bazett’s Correction
23. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gast
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method