Palliative Thoracic Radiotherapy Plus BKM120
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: BKM120
Intervention description: Buparlisib is a highly specific inhibitor of phosphatidylinositol 3-kinase (PI3K). Buparlisib is supplied as 10mg and 50mg hard gelatin capsules.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lung cancer; BKM120; Hypoxia; Misonidazole; Radiotherapy; Buparlisib

Summary:

      This study will test whether a drug called BKM120/buparlisib is a safe and effective
      treatment when given to lung cancer patients having radiotherapy treatment. The trial will
      identify which of three possible doses of buparlisib is best to give with lung radiotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Evidence of histologically confirmed NSCLC of any stage

          -  Thoracic lesion requiring palliative radiotherapy and which has been identified on a
             scan within eight weeks of starting the trial.

          -  Male or female, age ≥ 18 years at the day of consenting to the study.

          -  Life expectancy of at least 16 weeks.

          -  ECOG performance score of 0-2.

          -  Patient is able to swallow and retain oral medication.

          -  The patient is willing to provide written informed consent and is likely to comply
             with the protocol for the duration of the study, and scheduled follow-up visits and
             examinations.

          -  Haematological and biochemical indices within the ranges shown below:

               -  Haemoglobin (Hb) ≥ 9.0 g/dL

               -  Absolute neutrophil count ≥ 1.5 x 109/L

               -  Platelet count ≥100 x 109/L

               -  International Normalised Ratio (INR) ≤ 1.5

               -  Potassium, calcium and Magnesium within normal range

               -  ALT and AST not above normal range or ≤3.0 times ULN if liver metastases are
                  present

               -  Total serum bilirubin not above normal range, or ≤1.5 times ULN if liver
                  metastases are present or total bilirubin ≤3.0 times ULN if the patient has well
                  documented Gilbert's disease and absence of other contributing disease process at
                  the time of diagnosis

               -  Creatinine ≤ 1.5 x ULN

               -  Fasting plasma glucose (FPG) ≤ 120mg/dL [6.7 mmol/L]

        Exclusion Criteria:

          -  Previous chemotherapy or biological therapy within four weeks of starting study
             treatment.

          -  Treatment with any other investigational agent, or participation in another
             interventional clinical trial within 28 days prior to enrolment.

          -  Patient has not recovered to grade 1 or better (except alopecia) from related side
             effects of any prior antineoplastic therapy.

          -  Treatment at the start of study treatment with any drugs known to be moderate or
             strong inhibitors or inducers of isoenzyme CYP3A4, and the treatment cannot be
             discontinued or switched to a different medication prior to starting study drug.

          -  Presence of active uncontrolled or symptomatic CNS metastases. Patients with
             asymptomatic CNS metastases may participate in this trial. Any prior local treatment
             for CNS metastases must have been completed treatment ≥ 28 days prior to enrolment in
             the trial (including surgery and radiotherapy).

          -  Patient has poorly controlled diabetes mellitus (HbA1c > 8 %)

          -  Previous exposure to PI3K, mTOR, or AKT inhibitor

          -  Patient has a known hypersensitivity to any of the excipients of BKM120

          -  Previous thoracic radiotherapy treatment

          -  Any previous extra-thoracic radiotherapy within 28 days prior to enrolment

          -  Medically documented history of or active major depressive episode, bipolar disorder,
             obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or
             ideation, or risk of doing harm to others

          -  Patient meets the cut-off score of ≥ 12 in the PHQ-9 or a cut-off of ≥ 15 in the GAD-7
             mood scale, respectively, or selects a positive response of '1, 2, or 3' to question
             number 9 regarding potential for suicidal thoughts ideation in the PHQ-9 (independent
             of the total score of the PHQ-9)

          -  Patient has ≥CTCAE grade 3 anxiety

          -  Other psychological, social or medical condition, physical examination finding or a
             laboratory abnormality that the Investigator considers would make the patient a poor
             trial candidate or could interfere with protocol compliance or the interpretation of
             trial results.

          -  Patient has a concurrent malignancy or has had any malignancy (other than NSCLC) in
             the last 3 years prior to start of study treatment (with the exception of adequately
             treated basal or squamous cell carcinoma or cervical carcinoma in situ)

          -  Patient has had major surgery within 14 days of starting the study drug.

          -  Patient has any other concurrent severe, and/or uncontrolled medical condition that
             would, in the investigator's judgement contraindicate patient participation in the
             clinical study (e.g. chronic pancreatitis, chronic active hepatitis).

          -  Patient has impairment of gastrointestinal (GI) function or GI disease that may
             significantly alter the absorption of BKM120.

          -  Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or
             HIV.

          -  Patient has active cardiac disease or a history of myocardial infarction within 6
             months of entering the trial, congestive heart failure ( New York Heart Association
             functional classification III-IV) or documented cardiomyopathy

          -  Pregnant or breast-feeding women, or women of childbearing potential unless effective
             methods of contraception are used. Oral contraception, injected or implanted hormonal
             methods are not allowed as BKM120 potentially decreases the effectiveness of hormonal
             contraceptives. Women of child-bearing potential must have a negative serum pregnancy
             test less than 72 hours prior to initiating treatment