Esophageal Squamous Cell CarcinomaPhase 1NCT01822613
Study of Safety & Efficacy of the Combination of LJM716 & BYL719 in Patients With Previously Treated Esophageal Squamous Cell Carcinoma (ESCC)
A Phase 1 study testing LJM716, BYL719 and Paclitaxel in people with Esophageal Squamous Cell Carcinoma, run by Novartis Pharmaceuticals at 13 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophageal Squamous Cell Carcinoma
- What is being tested?
- LJM716, BYL719 and Paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 13 sitesin 9 countries
- Study dates
- 26 Jul 2013to 3 Jun 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
13 sites in 9 countries.
13 sites in 9 countries
United States3 sites
University of Chicago Medical Center Dept of Onc
Chicago, Illinois, 60637
Karmanos Cancer Institute Dept of Onc
Detroit, Michigan, 48201
University of Texas/MD Anderson Cancer Center Gastrointestinal Med. Oncology
Houston, Texas, 77030-4009
South Korea2 sites
Novartis Investigative Site
Seoul, Korea, 03080
Novartis Investigative Site
Seoul, Korea, 05505
Taiwan2 sites
Novartis Investigative Site
Tainan, Taiwan ROC, 70421
Novartis Investigative Site
Taipei, 10048
About this study
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)
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.
Read the 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.
- Conditions
- Esophageal Squamous Cell Carcinoma
- Being tested
- LJM716, BYL719, Paclitaxel, Docetaxel, Irinotecan
- Keywords
- esophageal cancer
- Medical subject headings
- Esophageal Squamous Cell Carcinoma, Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LJM716Drug
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.
BYL719Drug
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.
PaclitaxelDrug
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.
DocetaxelDrug
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.
IrinotecanDrug
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
| Study group | Role | What they receive |
|---|---|---|
| LJM716-BYL719 arm | Experimental | 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). Receives: Drug: LJM716; Drug: BYL719 |
| Paclitaxel, Docetaxel or Irinotecan arm | Active comparator | 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). Receives: Drug: Paclitaxel; Drug: Docetaxel; Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase Ib primary outcome measure: Incidence rate of dose limiting toxicities (DLTs).
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.
Measured: approximately 8 months
Phase II primary outcome measure: Progression free survival (PFS)
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.
Measured: 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 (8)
Safety and tolerability of the LJM716-BYL719
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.
Measured: Every 21 days from the date of the baseline visit until the end of study visit (about 5 months)
Best overall response (BOR), per RECIST 1.1 (Ph 1b )
BOR will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.
Measured: Every 21 days from the date of baseline computed tomography (CT) scan until end of treatment visit (about 4 months)
Plasma concentration versus time profiles Plasma PK parameters of LJM716, BYL719
Plasma concentration versus time profiles Plasma PK parameters will be used to characterize the PK profiles of LJM716 and BYL719 when used in combination
Measured: 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)
Overall response rate (ORR) per RECIST 1.1 (Ph 1b )
Overall response rate will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.
Measured: Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months)
Duration of response (DOR) per RECIST 1.1 (Ph 1b )
Duration of response will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.
Measured: Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months)
Disease control rate (DCR) per RECIST 1.1 (Ph 1b )
Disease control rate will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.
Measured: Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months)
Overall survival (OS) per RECIST 1.1 (for Ph 1b )
Overall survival will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.
Measured: Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months)
Progression free survival (PFS) per RECIST 1.1 (Ph 1b )
Progression free survival will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.
Measured: Every 21 days from the date of the baseline computed tomography (CT) scan until the end of study visit (about 5 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2013 (estimated)
- Study start26 Jul 2013
- Primary completion3 Jun 2016
- Study completion3 Jun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Esophageal Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01822613
- Sponsor's protocol ID
- CLJM716X2103
- Status last verified
- May 2017
- First submitted
- 22 Mar 2013
- Last updated
- 19 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01822613
- Acronym / sponsor ID
- CLJM716X2103
- Conditions
- Esophageal Squamous Cell Carcinoma
- Keywords
- esophageal cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 26 Jul 2013 (actual)
- Primary completion
- 3 Jun 2016 (actual)
- Study completion
- 3 Jun 2016 (actual)
- First posted
- 2 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LJM716-BYL719 arm | Experimental | Drug: LJM716, Drug: BYL719approximately 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). |
| Paclitaxel, Docetaxel or Irinotecan arm | Active comparator | Drug: Paclitaxel, Drug: Docetaxel, Drug: Irinotecanapproximately 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LJM716LJM716 (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. | Drug | LJM716-BYL719 arm |
| BYL719BYL719 (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. | Drug | LJM716-BYL719 arm |
| PaclitaxelIn 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. | Drug | Paclitaxel, Docetaxel or Irinotecan arm |
| DocetaxelIn 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. | Drug | Paclitaxel, Docetaxel or Irinotecan arm |
| IrinotecanIn 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 | Drug | Paclitaxel, Docetaxel or Irinotecan arm |
Primary outcome
Phase Ib primary outcome measure: Incidence rate of dose limiting toxicities (DLTs).
Time frame: approximately 8 months
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.
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.
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.
8 secondary outcomes
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)
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)
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)
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)
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)
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)
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)
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2020.
- Results for CLJM716X2103 from the Novartis Clinical Trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Esophageal Squamous Cell Carcinoma
RecruitingObservational study
Multicenter Prospective Cohort on Esophageal Endoscopic Submucosal Dissection
Superficial Esophageal Cancer, Oesophageal Adenocarcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer
Recruiting
Individually Tailored, Supervised, Remote Exercise Intervention to Improve Physical Function for Stage I-III Gastroesophageal Cancer Survivors, PRECISE Trial
Clinical Stage I Esophageal Adenocarcinoma American Joint Committee on Cancer (AJCC) v8, Clinical Stage I Esophageal Squamous Cell Carcinoma AJCC v8
Not yet recruitingObservational study
Standardized Management of Esophageal Fistula in Esophageal Squamous Cell Carcinoma
Esophageal Squamous Cell Carcinoma (ESCC), Esophageal Fistula
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
13 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LJM716, BYL719 and Paclitaxel in people with Esophageal Squamous Cell Carcinoma, run by Novartis Pharmaceuticals at 13 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, South Korea, Taiwan, Belgium, Canada and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase Ib primary outcome measure: Incidence rate of dose limiting toxicities (DLTs). (time frame: approximately 8 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2020.