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Phase 1 Completed N=21 Treatment

Palliative Thoracic Radiotherapy Plus BKM120

Source: ClinicalTrials.gov NCT02128724 ↗
Enrolled (actual)
21
Serious AEs
23.8%
Results posted
Aug 2019
Primary outcomePrimary: Dose Escalation Analysis: Number of DLTs Observed in Evaluable Patients — 0; 0; 0 Participants

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.

Outcome Measures

OutcomeResultp-value
PRIMARY
Dose Escalation Analysis: Number of DLTs Observed in Evaluable Patients
0; 0; 0
PRIMARY
Safety and Tolerability Analysis: Patients With Buparlisib Related Adverse Events
1; 2; 1; 1; 2; 5
SECONDARY
Changes in 18F-Misonidazole Uptake as Detected by PET-CT Scans: Response
0; 3; 7; 3; 0; 2
SECONDARY
Blood Flow at Days -1 and 8 as Detected by Perfusion CT
64.2; 102.2; 63.9; 60.2; 63.9; 64.5
SECONDARY
Tumour-to-blood Volume Ratio in 18F-Misonidazole Uptake as Detected by Day -1 and Day 8 PET-CT Scans, to Investigate if Buparlisib Alters Hypoxia
44.4; 51.3; 33.1; 47.6; 42.2; 25.4
SECONDARY
Changes in Blood Flow as Detected by Perfusion CT: Response
2; 0; 3; 1; 3; 5
SECONDARY
Percentage Change in Blood Flow as Detected by Perfusion CT at Days -1 and 8
1.4; -17.5; -15.0
SECONDARY
Tumour-to-blood Mean Ratio in 18F-Misonidazole Uptake as Detected by PET-CT Scans, to Investigate if Buparlisib Alters Hypoxia
1.34; 1.2; 1.23; 1.41; 1.07; 1.17
SECONDARY
Tumour-to-blood Volume Ratio Percentage Changes Between Day -1 and Day 8 in 18F-Misonidazole Uptake as Detected by PET-CT Scans, to Investigate if Buparlisib Alters Hypoxia
7.1; -17.6; -19.9
SECONDARY
Percentage Changes in Blood Volume Between Day -1 and Day 8 as Detected by Perfusion CT
-11.1; -25.0; -21.2
SECONDARY
Blood Volume at Day -1 and Day 8 as Detected by Perfusion CT
4.0; 6.5; 5.8; 3.8; 4.7; 5.6
SECONDARY
Mean Transit Time as Detected by Perfusion CT at Days -1 and 8
8.6; 7.8; 7.4; 6.2; 6.2; 6.7
SECONDARY
Percentage Change in Mean Transit Time as Detected by Perfusion CT at Days -1 and 8
-25.9; -3.1; -12.6

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 significantl
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02128724). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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