Study of Safety & Efficacy of the Combination of LJM716 & BYL719 in Patients With Previously Treated Esophageal Squamous Cell Carcinoma (ESCC)

NCT01822613 | Completed Phase 1 FDA Drug

• 1 other identifier: CLJM716X2103
• Study Type: interventional
• Target: 48
• Locations: 9 countries
• Sites: 13

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.

Conditions

Esophageal Squamous Cell Carcinoma

Keywords

esophageal cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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

  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 )

  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

  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 )

  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 )

  Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months)

Study Arms (2)

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).

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).

Drug: Paclitaxel; Drug: Docetaxel; Drug: Irinotecan

Interventions

LJM716 DRUG

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.

LJM716-BYL719 arm

BYL719 DRUG

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.

LJM716-BYL719 arm

Paclitaxel DRUG

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.

Paclitaxel, Docetaxel or Irinotecan arm

Docetaxel DRUG

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.

Paclitaxel, Docetaxel or Irinotecan arm

Irinotecan DRUG

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

Paclitaxel, Docetaxel or Irinotecan arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (13)

University of Chicago Medical Center Dept of Onc

Chicago, Illinois, 60637, United States

Location

Karmanos Cancer Institute Dept of Onc

Detroit, Michigan, 48201, United States

Location

University of Texas/MD Anderson Cancer Center Gastrointestinal Med. Oncology

Houston, Texas, 77030-4009, United States

Location

Novartis Investigative Site

Brussels, 1200, Belgium

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Novartis Investigative Site

Hong Kong, Hong Kong

Location

Novartis Investigative Site

Singapore, 169610, Singapore

Location

Novartis Investigative Site

Seoul, Korea, 03080, South Korea

Location

Novartis Investigative Site

Seoul, Korea, 05505, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Tainan, Taiwan ROC, 70421, Taiwan

Location

Novartis Investigative Site

Taipei, 10048, Taiwan

Location

Novartis Investigative Site

Manchester, M20 2BX, United Kingdom

Location

Related Links

• Results for CLJM716X2103 from the Novartis Clinical Trials website

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma; Esophageal Neoplasms

Interventions

elgemtumab; Alpelisib; Paclitaxel; Docetaxel; Irinotecan

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2013
• First Posted: April 2, 2013
• Study Start: July 26, 2013
• Primary Completion: June 3, 2016
• Study Completion: June 3, 2016
• Last Updated: December 19, 2020

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); TW (2); SG (1); CA (1); BE (1); HK (1); KR (2); GB (1); ES (1)