Clinical trial NCT01822613: Study of Safety & Efficacy of the Combination of LJM716 & BYL719 in Patients With Previously Treated Esophageal Squamous Cell Carcinoma (ESCC)
Official 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 (ESCC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Esophageal Squamous Cell Carcinoma
Keywords: esophageal cancer
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-04-02
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To study the safety and efficacy of the combination of LJM716 and BYL719 against currently available treatments of physician's choice in previously treated esophageal squamous cell carcinoma patients.

Detailed description: The study design included a Phase 1b dose escalation portion to define the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) for the combination of LJM716 and alpelisib, followed by an open-label, randomized Phase 2 part to compare anti-tumor activity of LJM716-alpelisib combination versus physician's choice of second-line therapy (paclitaxel, docetaxel, irinotecan). However, the phase 2 part was not conducted as the study was terminated early due to limited anti-tumor activity with LJM716-alpelisib combination observed in phase 1b.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed esophageal squamous cell carcinoma (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 platinum-based chemotherapy or chemoradiotherapy for localized disease.

Exclusion Criteria:

* Patients who received prior phosphoinositide-3-kinase (PI3K) inhibitor or anti-receptor tyrosine-protein kinase erbB-3 (ERBB3 or HER3) antibody treatment, including bi-specific antibodies with HER3 as one of the targets (patients with prior exposure to pertuzumab or epidermal growth factor receptor (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 system (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 inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Phase Ib primary outcome measure: Incidence rate of dose limiting toxicities (DLTs).
timeFrame: approximately 8 months
measure: Phase II primary outcome measure: Progression free survival (PFS)
timeFrame: Every 6 weeks from the date of the baseline computed-tomography (CT) scan until the date of first documented evidence of disease progression or date of death, whichever comes first, assessed up to 24 months.
Secondary outcomes:
measure: Safety and tolerability of the LJM716-BYL719
timeFrame: Every 21 days from the date of the baseline visit until the end of study visit (about 5 months)
measure: Best overall response (BOR), per RECIST 1.1 (Ph 1b )
timeFrame: Every 21 days from the date of baseline computed tomography (CT) scan until end of treatment visit (about 4 months)
measure: Plasma concentration versus time profiles Plasma PK parameters of LJM716, BYL719
timeFrame: 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)
measure: Overall response rate (ORR) per RECIST 1.1 (Ph 1b )
timeFrame: Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months)
measure: Duration of response (DOR) per RECIST 1.1 (Ph 1b )
timeFrame: Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months)
measure: Disease control rate (DCR) per RECIST 1.1 (Ph 1b )
timeFrame: Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months)
measure: Overall survival (OS) per RECIST 1.1 (for Ph 1b )
timeFrame: Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months)
measure: Progression free survival (PFS) per RECIST 1.1 (Ph 1b )
timeFrame: Every 21 days from the date of the baseline computed tomography (CT) scan until the end of study visit (about 5 months)
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Medical Center Dept of Onc
state: Illinois
city: Detroit
country: United States
facility: Karmanos Cancer Institute Dept of Onc
state: Michigan
city: Houston
country: United States
facility: University of Texas/MD Anderson Cancer Center Gastrointestinal Med. Oncology
state: Texas
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Tainan
country: Taiwan
facility: Novartis Investigative Site
state: Taiwan ROC
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: