AZD9291 Versus Placebo in Patients With Stage IB-IIIA Non-small Cell Lung Carcinoma, Following Complete Tumour Resection With or Without Adjuvant Chemotherapy.
Condition: Stage IB-IIIA Non-small Cell Lung Carcinoma
MeSH terms: Carcinoma; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: AZD9291 80 mg/40 mg; Placebo AZD9291 80 mg/40 mg; Open-label AZD9291 80 mg/40 mg
Intervention description: The initial dose of AZD9291 80 mg once daily can be reduced to 40 mg once daily.; The initial dose of Placebo AZD9291 80 mg once daily can be reduced to 40 mg once daily.; Eligible patients will be offered open-label osimertinib upon recurrence and in the absence of intervening systemic anti-cancer therapy.
Intervention MeSH terms: Osimertinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 682.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Stage IB-IIA-IIIA Non-Small Cell Lung Cancer; EGFRm+; Ex19Del; L858R; AZD9291; Phase III, adjuvant chemotherapy; complete tumour resection; EGFR-TKI

Summary:

      To assess the efficacy and safety of AZD9291 versus Placebo, in patients with Epidermal
      Growth Factor Receptor Mutation Positive stage IB-IIIA non-small cell lung carcinoma,
      following complete tumour resection with or without adjuvant chemotherapy
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female, aged at least 18 years.

          2. Histologically confirmed diagnosis of primary non small lung cancer (NSCLC) on
             predominantly non-squamous histology

          3. MRI or CT scan of the brain must be done prior to surgery as it is considered standard
             of care.

          4. Patients must be classified post-operatively as Stage IB, II or IIIA on the basis of
             pathologic criteria.

          5. Confirmation by the central laboratory that the tumour harbours one of the 2 common
             EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R),
             either alone or in combination with other EGFR mutations including T790M.

          6. Complete surgical resection of the primary NSCLC is mandatory. All gross disease must
             have been removed at the end of surgery. All surgical margins of resection must be
             negative for tumour.

          7. Complete recovery from surgery and standard post-operative therapy (if applicable) at
             the time of randomization.

          8. World Health Organization Performance Status of 0 to 1.

          9. Female patients should be using adequate contraceptive measures, should not be breast
             feeding, and must have a negative pregnancy test prior to first dose of study drug; or
             female patients must have an evidence of non-child-bearing potential.

        Exclusion Criteria:

          1. Treatment with any of the following:

               -  Pre-operative or post-operative or planned radiation therapy for the current lung
                  cancer

               -  Pre-operative (neo-adjuvant) platinum based or other chemotherapy

               -  Any prior anticancer therapy

               -  Prior treatment with neoadjuvant or adjuvant EGFR-TKI at any time

               -  Major surgery (including primary tumour surgery, excluding placement of vascular
                  access) within 4 weeks of the first dose of study drug

               -  Patients currently receiving medications or herbal supplements known to be potent
                  inducers of cytochrome P450 (CYP) 3A4

               -  Treatment with an investigational drug within five half-lives of the compound or
                  any of its related material.

          2. Patients who have had only segmentectomies or wedge resections

          3. History of other malignancies, except: adequately treated non-melanoma skin cancer,
             curatively treated in-situ cancer, or other solid tumours curatively treated with no
             evidence of disease for > 5 years following the end of treatment.

          4. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of
             starting study treatment with the exception of alopecia and Grade 2, prior
             platinum-therapy related neuropathy.

          5. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled
             hypertension and active bleeding diatheses; or active infection including hepatitis B,
             hepatitis C and human immunodeficiency virus (HIV).

          6. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to
             swallow the formulated product, or previous significant bowel resection that would
             preclude adequate absorption of AZD9291.

          7. Any of the following cardiac criteria:

               -  Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using
                  the screening clinic ECG machine-derived QTc value.

               -  Any clinically important abnormalities in rhythm, conduction, or morphology of
                  resting ECG.

               -  Any factors that increase the risk of QTc prolongation or risk of arrhythmic
                  events, or unexplained sudden death under 40 years of age in first-degree
                  relatives or any concomitant medication known to prolong the QT interval.

          8. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required
             steroid treatment, or any evidence of clinically active ILD.

          9. Inadequate bone marrow reserve or organ function.