Study of safety & efficacy of the combination of LJM716 & BYL719 in patients with previously treated esophageal squamous cell carcinoma (ESCC)

• Register: EUCTR
• Last refreshed on: 8 August 2016
• Main ID: EUCTR2012-005624-15-BE
• Date of registration: 22/05/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Study of safety & efficacy of the combination of LJM716 & BYL719 in patients with previously treated esophageal squamous cell carcinoma (ESCC)
• Scientific title: A phase Ib/II, open-label study of LJM716 in combination with BYL719 compared to taxane or irinotecan in patients with previously treated esophageal squamous cell carcinoma
• Date of first enrolment: 11/06/2013
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-005624-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, France, Hong Kong, Japan, Korea, Republic of, Singapore, Spain, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

Key inclusion & exclusion criteria

Inclusion criteria:
- Histologically confirmed ESCC
- No more than one prior chemotherapy regimen for recurrent or metastatic ESCC (for Phase II only).
- Progression during or after platinum-based therapy for recurrent or metastatic ESCC, or recurrence within 6 months of platinumbased chemotherapy or chemoradiotherapy for localized disease.
Other protocol-defined inclusion criteria may apply.
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 65
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 35

Exclusion criteria:
- Patients who received prior PI3K inhibitor or anti-HER3 antibody treatment, including bi-specific antibodies with HER3 as one of the targets (patients with prior exposure to pertuzumab or EGFR-targeted agents are eligible)
- Patients who do not have an archival or fresh tumor sample (or sections of it)
available or readily obtainable.
- Patients with central nervous sytem (CNS) metastatic involvement.
- Patients who have received prior systemic anti-cancer treatment, such as cyclical chemotherapy or biological therapy within a period of time that is shorter than the cycle length used for that treatment (e.g. 6 weeks for nitrosourea, mitomycin-C) prior to starting study treatment.
- Patients who have received definitive radiotherapy = 4 weeks prior to starting study drug, who have not recovered from side effects of such therapy and/or from whom = 30% of the bone marrow was irradiated.
Other protocol-defined exclusion criteria may apply.


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

Health Condition(s) or Problem(s) studied

esophageal squamous cell carcinoma

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

Intervention(s)

Product Code: LJM716
Pharmaceutical Form: Powder for solution for infusion
Current Sponsor code: LJM716
Other descriptive name: LJM716
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-

Product Code: BYL719
Pharmaceutical Form: Tablet
Current Sponsor code: BYL719
Other descriptive name: BYL719
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Trade Name: Paclitaxel Sandoz
Product Name: paclitaxel
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Other descriptive name: paclitaxel
Concentration unit: ml millilitre(s)
Concentration type: equal
Concentration number: 16,7-

Product Code: BYL719
Pharmaceutical Form: Tablet
Current Sponsor code: BYL719
Other descriptive name: BYL719
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Code: BYL719
Pharmaceutical Form: Tablet
Current Sponsor code: BYL719
Other descriptive name: BYL719
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: Paclitaxel Sandoz
Product Name: paclitaxel
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Other descriptive name: paclitaxel
Concentration unit: ml millilitre(s)
Concentration type: equal
Concentration number: 5-

Trade Name: Paclitaxel Sandoz
Product Name: paclitaxel
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Other descriptive name: paclitaxel
Concentration unit: ml millilitre(s)
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. approximately 8 months
2. Baseline, every 6 weeks until disease progression

Primary end point(s): 1. Phase Ib primary end point: Incidence rate of DLTs.
2. Phase II primary end point: Progression free survival (PFS)

Main Objective: To study the safety and efficacy of the combination of LJM716 and BYL719 against currently available treatments of physician’s choice in previously treated ESCC patients

Secondary Objective: tolerability, PFS, OOS

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Baseline, every 21 days until end of study (about 5 months)
2. Baseline, every 21 days until end of treatment (about 4 months)
3. Baseline, 2hr,4hr,8hr,24hr,48hr,96hr, 168 hr, every 21 days for 10 cycles (21 days each) and at end of treatment (about 4 months)
4-6. Baseline, every 21 days until end of treatment (about 4 months)
7-8. Baseline, every 21 days until end of study (about 5 months)

Secondary end point(s): 1. Safety and tolerability of the LJM716-BYL719
2. Best overall response (BOR), per RECIST 1.1 (Ph 1b )
3. Plasma concentration versus time profiles; Plasma PK parameters of LJM716, BYL719
4. Overall response rate (ORR) per RECIST 1.1 (Ph 1b )
5. Duration of response (DOR) per RECIST 1.1 (Ph 1b )
6. Disease control rate (DCR) per RECIST 1.1 (Ph 1b )
7. Overall survival (OS) per RECIST 1.1 (for Ph 1b )
8. Progression free survival (PFS) per RECIST 1.1 (Ph 1b )

Secondary ID(s)

CLJM716X2103

2012-005624-15-ES

Source(s) of Monetary Support

Novartis Pharma Services AG