- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01822613
Study of Safety & Efficacy of the Combination of LJM716 & BYL719 in Patients With Previously Treated Esophageal Squamous Cell Carcinoma (ESCC)
December 16, 2020 updated by: Novartis Pharmaceuticals
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)
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
48
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Bruxelles, Belgium, 1200
- Novartis Investigative Site
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Ontario
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Toronto, Ontario, Canada, M5G 2M9
- Novartis Investigative Site
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Hong Kong, Hong Kong
- Novartis Investigative Site
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Korea
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Seoul, Korea, Korea, Republic of, 05505
- Novartis Investigative Site
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Seoul, Korea, Korea, Republic of, 03080
- Novartis Investigative Site
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Singapore, Singapore, 169610
- Novartis Investigative Site
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Catalunya
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Barcelona, Catalunya, Spain, 08035
- Novartis Investigative Site
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Taipei, Taiwan, 10048
- Novartis Investigative Site
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Taiwan ROC
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Tainan, Taiwan ROC, Taiwan, 70421
- Novartis Investigative Site
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Manchester, United Kingdom, M20 2BX
- Novartis Investigative Site
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Illinois
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Chicago, Illinois, United States, 60637
- University of Chicago Medical Center Dept of Onc
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Michigan
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Detroit, Michigan, United States, 48201
- Karmanos Cancer Institute Dept of Onc
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Texas
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Houston, Texas, United States, 77030-4009
- University of Texas/MD Anderson Cancer Center Gastrointestinal Med. Oncology
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: LJM716-BYL719 arm
approximately 42 previously treated esophageal squamous cell carcinoma (ESCC) patients will be enrolled to the LJM716-BYL719 combination arm to evaluate the anti-tumor activity and further assess the safety, tolerability and anti-tumor activity of the combination versus current therapies (physician's choice of paclitaxel, docetaxel or irinotecan).
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LJM716 (10-40 mg/kg) will be given as a once weekly infusion beginning on cycle 1 day 1.
The doses of LJM716 will be increased as dose escalation proceeds until a maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) is established.
BYL719 (200-400 mg) will be administered orally on a once daily schedule starting cycle 1 day 1.
The doses of BYL719 will be increased as dose escalation proceeds until a maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) is established.
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ACTIVE_COMPARATOR: Paclitaxel, Docetaxel or Irinotecan arm
approximately 42 previously treated esophageal squamous cell carcinoma (ESCC) patients will be enrolled to the Paclitaxel, Docetaxel or Irinotecan arm (physician's choice arm) to evaluate the anti-tumor activity and further assess the safety, tolerability and anti-tumor activity of the LJM716-BYL719 combination versus current therapies (physician's choice of paclitaxel, docetaxel or irinotecan).
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In the Phase II portion of the study Paclitaxel is one of the 3 physician's choice drug which allows single-agent paclitaxel to be used per manufacturer's label.
In the Phase II portion of the study Docetaxel is one of the 3 physician's choice drug which allows single-agent docetaxel to be used per manufacturer's label.
In the Phase II portion of the study Irinotecan is one of the 3 physician's choice drug which allows single-agent irinotecan to be used per manufacturer's label
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Phase Ib primary outcome measure: Incidence rate of dose limiting toxicities (DLTs).
Time Frame: approximately 8 months
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The open-label dose escalation part of the study will be guided by a well-established statistical method/model to estimate the maximum tolerated dose(s) and/or Recommended Phase II Dose (s) guided by the safety (incidence of dose limiting toxicities), efficacy, pharmacokinetics and pharmacodynamics data.
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approximately 8 months
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Phase II primary outcome measure: Progression free survival (PFS)
Time Frame: 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.
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Progression-free survival is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause.
If a patient has not had an event, progression-free survival is censored at the date of last adequate assessment.
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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.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Safety and tolerability of the LJM716-BYL719
Time Frame: Every 21 days from the date of the baseline visit until the end of study visit (about 5 months)
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This will be assessed by looking at the number of Adverse Events (AEs), serious AEs (SAEs) changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, reductions and dose intensity.
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Every 21 days from the date of the baseline visit until the end of study visit (about 5 months)
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Best overall response (BOR), per RECIST 1.1 (Ph 1b )
Time Frame: Every 21 days from the date of baseline computed tomography (CT) scan until end of treatment visit (about 4 months)
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BOR will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.
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Every 21 days from the date of baseline computed tomography (CT) scan until end of treatment visit (about 4 months)
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Plasma concentration versus time profiles Plasma PK parameters of LJM716, BYL719
Time Frame: 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)
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Plasma concentration versus time profiles Plasma PK parameters will be used to characterize the PK profiles of LJM716 and BYL719 when used in combination
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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)
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Overall response rate (ORR) per RECIST 1.1 (Ph 1b )
Time Frame: Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months)
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Overall response rate will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.
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Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months)
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Duration of response (DOR) per RECIST 1.1 (Ph 1b )
Time Frame: Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months)
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Duration of response will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.
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Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months)
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Disease control rate (DCR) per RECIST 1.1 (Ph 1b )
Time Frame: Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months)
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Disease control rate will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.
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Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months)
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Overall survival (OS) per RECIST 1.1 (for Ph 1b )
Time Frame: Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months)
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Overall survival will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.
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Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months)
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Progression free survival (PFS) per RECIST 1.1 (Ph 1b )
Time Frame: Every 21 days from the date of the baseline computed tomography (CT) scan until the end of study visit (about 5 months)
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Progression free survival will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.
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Every 21 days from the date of the baseline computed tomography (CT) scan until the end of study visit (about 5 months)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
July 26, 2013
Primary Completion (ACTUAL)
June 3, 2016
Study Completion (ACTUAL)
June 3, 2016
Study Registration Dates
First Submitted
March 22, 2013
First Submitted That Met QC Criteria
March 27, 2013
First Posted (ESTIMATE)
April 2, 2013
Study Record Updates
Last Update Posted (ACTUAL)
December 19, 2020
Last Update Submitted That Met QC Criteria
December 16, 2020
Last Verified
May 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Head and Neck Neoplasms
- Esophageal Diseases
- Neoplasms, Squamous Cell
- Esophageal Neoplasms
- Carcinoma
- Carcinoma, Squamous Cell
- Esophageal Squamous Cell Carcinoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Topoisomerase Inhibitors
- Topoisomerase I Inhibitors
- Docetaxel
- Paclitaxel
- Irinotecan
Other Study ID Numbers
- CLJM716X2103
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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