clinical research study to find out if buparlisib (BKM120) in combination with docetaxel therapy is safe and has beneficial effects in people who have advanced or metastatic squamous non-small cell lung cancer and were previously treated with platinum-based chemotherapy.

• Register: EUCTR
• Last refreshed on: 23 February 2015
• Main ID: EUCTR2013-000833-11-HU
• Date of registration: 13/12/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: clinical research study to find out if buparlisib (BKM120) in combination with docetaxel therapy is safe and has beneficial effects in people who have advanced or metastatic squamous non-small cell lung cancer and were previously treated with platinum-based chemotherapy.
• Scientific title: A Phase Ib/II study of docetaxel with or without buparlisib as second line therapy for patients with advanced or metastatic squamous non-small cell lung cancer - Basalt 3
• Date of first enrolment: 05/02/2014
• Target sample size: 211
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000833-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, China, Colombia, France, Germany, Hong Kong, Hungary, Italy, Japan, Korea, Republic of, Norway, Poland, Russian Federation, Slovakia, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom, United States

Key inclusion & exclusion criteria

Inclusion criteria:
•Patient is an adult = 18 years old at the time of informed consent
•Patient has histologically and/or cytologically confirmed diagnosis of squamous NSCLC. Diagnosis of mixed squamous and non-squamous or adenosquamous NSCLC will be acceptable for enrollment.
•Patient has received one prior approved regimen of platinum-based chemotherapy (excluding a docetaxel-containing regimen) for advanced or metastatic (Stage IIIb or Stage IV) squamous NSCLC, followed by disease progression. A drug provided as maintenance therapy following cytotoxic chemotherapy will be considered to be part of that regimen.
Note: Patients who received paclitaxel therapy are eligible for this trial.
•Patient has adequate tumor tissue (either archival or new tumor biopsy) for the analysis of PI3K-related biomarkers.
- Enrollment in the Phase II part of the study is contingent on the central laboratory confirming receipt of an adequate amount of tissue including sufficient DNA for analysis.
•Patient has measurable or non-measurable disease according to RECIST version 1.1 criteria.
- Phase II only: Patient must have at least one measurable lesion as per RECIST criteria.
•Patient has an ECOG performance status = 1
•Patient has adequate bone marrow and organ function

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
•Patient has received previous treatment with a PI3K or AKT inhibitor
•Patient has symptomatic Central Nervous System (CNS) metastases
- Patients with asymptomatic CNS metastases may participate in this trial. The patient must have completed prior local treatment, if any, for CNS metastases = 28 days prior to the start of study treatment (including radiotherapy and/or surgery, or = 14 days for stereotactic radiosurgery).
•Patient has a score = 12 on the PHQ-9 questionnaire.
•Patient selects a response of “1, 2 or 3” to question number 9 on the PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9).
•Patient has a GAD-7 mood scale score = 15.
•Patient has a medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation or patients with active severe personality disorders.
•Patient has = CTCAE grade 3 anxiety


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

advanced/metastatic squamous non small cell lung cancer
MedDRA version: 16.1 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 16.1 Level: PT Classification code 10029521 Term: Non-small cell lung cancer stage IIIB System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 16.1 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 16.1 Level: PT Classification code 10001254 Term: Adenosquamous cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 16.1 Level: LLT Classification code 10001253 Term: Adenosquamous cell lung cancer stage IIIB System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: buparlisib
Product Code: BKM120
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Buparlisib
Current Sponsor code: BKM120
Other descriptive name: BKM120 HYDROCHLORIDE SALT
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: buparlisib
Product Code: BKM120
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Buparlisib
Current Sponsor code: BKM120
Other descriptive name: BKM120 HYDROCHLORIDE SALT
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: docetaxel
Pharmaceutical Form: Concentrate and solvent for concentrate for solution for infusion
INN or Proposed INN: Docetaxel
CAS Number: 148408-66-6
Other descriptive name: DOCETAXEL TRIHYDRATE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Product Name: docetaxel
Pharmaceutical Form: Concentrate and solvent for concentrate for solution for infusion
INN or Proposed INN: Docetaxel
CAS Number: 148408-66-6
Other descriptive name: DOCETAXEL TRIHYDRATE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Primary end point(s): - Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1
- Progression Free Survival (PFS)

Main Objective: For phase Ib:
To determine the maximum-tolerated dose (MTD) / recommended Phase II dose (RP2D) of buparlisib when administered orally in combination with every-3-week administration of docetaxel to adult patients with Stage IIIb or Stage IV NSCLC of squamous histology previously treated with platinum-based chemotherapy

For phase II:
To estimate the treatment effect of every-three-week administration of docetaxel and daily buparlisib or placebo on PFS in patients previously treated with platinum-based chemotherapy for advanced or metastatic squamous NSCLC

Secondary Objective: For phase Ib:
- Assess safety and tolerability
- Assess preliminary activity

For phase II:
- Assess safety and tolerability
- Assess additional efficacy parameters
- Understand the effect of docetaxel in combination with buparlisib or placebo on patients’ symptoms and health-related quality of life (HRQoL)
- Investigation of the PK of both buparlisib and docetaxel when administered in combination

Timepoint(s) of evaluation of this end point: - Day 21 for incidence of DLT
- After 70 PFS events have been observed at 9 months after patient enrollment for PFS

Secondary Outcome(s)

Secondary end point(s): 1. Number of patients with at least one adverse event
2. Number of patients with laboratory abnormalities
3. Overall Survival (OS)
4. Overall response rate (ORR)
5. Time to response (ToR)
6. Duration of response (DR)
7. Change in electrocardiogram (ECG) and cardiac imaging
8. Changes in vital signs
9. Shift in ECOG performance status
10. Change in Mood scales
11. Time to definitive 10% deterioration in the global health status/quality of life (QOL) scale score of the EORTC QLQ-C30
12. Change in the global health status/quality of life (QOL) scale score of the EORTC QLQ-C30
13. Docetaxel and buparlisib plasma concentrations
14. PFS Phase Ib)

Timepoint(s) of evaluation of this end point: Endpoints number:
1, 2, 7, 8 & 10: treatment start until 30 days after the last dose
3: : 8 months (Phase Ib) and from time of randomization to death (Phase II)
4: time from start date of study treatment in Phase Ib and from date of randomization in phase II to the date of first documented response
5: date of start of study treatment in Phase Ib and date of randomization in phase II to the date of first documented response
6: date of first documented response, the following date of event
9: Baseline, worst post-baseline result
11: date of randomization, date of event
12: baseline, at time of each assessment
13: cycle 1, end of treatment
14: start date of treatment, 3 months, date or progression or death

Secondary ID(s)

2013-000833-11-SE

CBKM120D2205

Source(s) of Monetary Support

Novartis Pharma Services AG