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Completed

NCT Number: NCT01822613

Study of Safety & Efficacy of the Combination of LJM716 & BYL719 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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Novartis Investigative Site, Brussels, Belgium

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

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.

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.

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.

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

Primary outcomes

  1. 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.

  2. 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.

Secondary outcomes

  1. 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)

    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.

  2. 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)

    BOR will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.

  3. 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)

    Plasma concentration versus time profiles Plasma PK parameters will be used to characterize the PK profiles of LJM716 and BYL719 when used in combination

  4. 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)

    Overall response rate will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.

  5. 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)

    Duration of response will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.

  6. 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)

    Disease control rate will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.

  7. 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)

    Overall survival will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.

  8. 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)

    Progression free survival will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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)

Important dates

Study start
2013
Primary completion
2016
Study completion
2016
First posted
Apr 2, 2013
Registry last updated
Dec 19, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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