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Neoplasms, Breast Neoplasms, Head and Neck NeoplasmsPhase 1NCT02051751

A Study to Evaluate the Potential Benefit of the Addition of BYL719 to Paclitaxel in the Treatment of Breast Cancer and Head-and-neck Cancer

A Phase 1 study testing BYL719 and Paclitaxel in people with Neoplasms, Breast Neoplasms, Head and Neck Neoplasms, run by Novartis Pharmaceuticals at 5 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Dose escalation part:to determine the highest dose of BYL719 administered on a daily basis when given in combination with weekly paclitaxel Dose escalation part: to confirm the safety and tolerability of the BYL719 and paclitaxel combination Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
BYL719 and Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
5 sitesin 4 countries
Study dates
5 Mar 2014to 19 Aug 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

  • - Adult > or = 18 years old
  • - has signed the Informed Consent Form (ICF)
  • - has at least one measurable or non-measurable disease as per RECIST 1.1
  • - has tumor tissue available for the analysis as described in the protocol
  • - has adequate bone marrow and organ function as defined in the protocol
  • - is able to swallow and retain oral medication for the dose escalation part, ALL above PLUS
Show all 34Show fewer
  • - has a histologically-confirmed, advanced unresectable solid tumors who have progressed on standard therapy (or not been able to tolerate) within three months before screening/baseline visit or for whom no standard anticancer therapy exists.
  • - has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2 For dose expansion part, patient has ALL of above first six criteria PLUS either: 9- has a histologically/cytologically-confirmed HNSCC as detailed in the protocol and an ECOG performance status ≤ 1 or:
  • Patient is a Female with a histologically and/or cytologically confirmed diagnosis of breast cancer as detailed in the protocol and an ECOG performance status ≤ 1
  • Common exclusion criteria to Dose escalation and Dose expansion parts:
  • - has received previous treatment with a PI3K or AKT inhibitor as described in the protocol
  • - has a known hypersensitivity to paclitaxel or other products containing Cremophor
  • - has a contraindication to use the standard pre-treatment for paclitaxel
  • - has a primary central nervous system (CNS) tumor or CNS tumor involvement as detailed in the protocol
  • - has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy
  • - has received radiotherapy > or = 4 weeks prior to starting study drugs, with exception of palliative radiotherapy, who has not recovered from side effects of such therapy to baseline or Grade ≤ 1 and/or from whom ≥ 30% of the bone marrow was irradiated
  • - has peripheral sensory neuropathy with functional impairment (CTC grade 2 neuropathy or higher)
  • - has undergone major surgery ≤ 4 weeks prior to starting study treatment or who has not recovered from side effects of such procedure
  • - has a clinically significant cardiac disease or impaired cardiac function as detailed in the protocol
  • - is currently receiving medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (TdP) and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug treatment
  • - has diabetes mellitus requiring insulin treatment and/or with clinical signs
  • - has impaired gastrointestinal (GI) function or GI disease as described in the protocol
  • - has a known positive serology for human immunodeficiency virus (HIV), active Hepatitis B, and/or active Hepatitis C infection
  • - has any other condition that would, in the Investigator's judgment, preclude patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures
  • - is currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzymes CYP3A or CYP2C8 as detailed in the protocol
  • - is currently receiving treatment with agents that are metabolized solely by CYP3A and/or have a narrow therapeutic window
  • - has a history of another malignancy within 2 years prior to starting study treatment, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix
  • - Patient has a history of non-compliance to medical regimen or inability to grant consent
  • - Pregnant or nursing (lactating) women
  • - does not apply highly effective contraception during the study and through the duration as defined in the protocol
  • For the HNSCC patient's cohort additional exclusion criteria are:
  • 21- Treatment with more than one prior chemotherapy for recurrent/metastatic disease as detailed in the protocol 22- Prior taxane treatment for metastatic disease additional exclusion criteria for breast cancer patients' cohort:
  • has received any prior cytotoxic therapy for the inoperable locally advanced (recurrent or progressive) or metastatic disease, or who had a progression/recurrent disease within 6 months after completion of an adjuvant/neoadjuvant therapy as described in the protocol
  • Other protocol-defined inclusion/exclusion criteria may apply

Who cannot join

None listed.

Trial locations and contacts

5 sites in 4 countries.

5 sites in 4 countries

United States2 sites

  • Highlands Oncology Group

    Fayetteville, Arkansas, 72703

  • Horizon Oncology Center BioAdvance

    Lafayette, Indiana, 47905

Other trials in United States

France1 site

  • Novartis Investigative Site

    Toulouse, 31059

Other trials in France

Italy1 site

  • Novartis Investigative Site

    Milan, MI, 20141

Other trials in Italy

Spain1 site

  • Novartis Investigative Site

    Barcelona, Catalonia, 08035

Other trials in Spain

About this study

Official title: A Phase Ib Open Label Dose Finding Study of BYL719 in Combination With Paclitaxel in Advanced Solid Tumors Followed by Two Expansion Phases in Locally Advanced/Metastatic Chemotherapy Naive HER2 Negative Breast Cancer Patients (HER2- mBC) and in Recurrent and Metastatic Head-and-neck Squamous Cell Carcinoma Patients (HNSCC) Pre-treated With Platinum Based Therapy

Dose escalation part:to determine the highest dose of BYL719 administered on a daily basis when given in combination with weekly paclitaxel Dose escalation part: to confirm the safety and tolerability of the BYL719 and paclitaxel combination

Being tested
BYL719, Paclitaxel
Keywords
Solid tumors, Head and neck non squamous cell carcinoma, breast cancer, PI3K inhibitor, BYL719, paclitaxel
Medical subject headings
Neoplasms, Breast Neoplasms, Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BYL719Drug

    BYL719 will be administered orally once daily on a continuous dosing schedule and dosed on a flat-fixed dose and not adjusted by body weight or body surface area, starting on Day 2 in the dose escalation part and Day 1 in the dose expansion part. In the dose escalation part, the BYL719 starting dose will be 300mg, with anticipated dose escalation to 350mg. In the dose expansion part, BYL719 will be administered at the recommended dose determined in the dose escalation part.

  • PaclitaxelDrug

    Paclitaxel will be administered once weekly at a dose of 80 mg/m2 i.v. (days 1, 8, 15 and 22) in a 28 day cycle in both dose escalation and expansion.

Study groups in NCT02051751
Study groupRoleWhat they receive
BYL719 and paclitaxelExperimentalAll patients enrolled in the study will receive BYL719 once daily plus weekly paclitaxel
Receives: Drug: BYL719; Drug: Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose escalation : Dose Limiting Toxicity (DLT)

    A dose-limiting toxicity (DLT) is an adverse event or abnormal laboratory value assessed as being unrelated to disease, disease progression, inter-current illness, or concomitant medications, and that occurs within the first cycle of treatment with BYL719 plus paclitaxel and meets any of the pre-defined criteria.

    Measured: Cycle 1 (28 days)

  2. Dose expansion : Number of patients with adverse events as a measure of safety and tolerability

    type, intensity, severity and seriousness of adverse events according to the NCI CTC AE v4.03. Dose interruptions, reductions and dose intensity.

    Measured: Screening, every 28 days until 30 days after last dose

Secondary outcomes (7)

  1. Dose escalation:Number of patients with adverse events as a measure of safety and tolerability

    type, intensity, severity and seriousness of adverse events according to the NCI CTC AE v4.03. Dose interruptions, reductions and dose intensity.

    Measured: Screening, every 28 days until 30 days after last dose

  2. Dose escalation : BYL719 and Paclitaxel Plasma concentrations

    Plasma concentration time profiles of BYL719 and paclitaxel. Plasma PK parameters of paclitaxel (single agent vs. combination) and BYL719 (steady state in combination with paclitaxel).

    Measured: Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9

  3. Dose expansion: Clinical benefit Rate in the breast cancer cohort

    Clinical benefit rate is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) for more than 24 weeks of duration of response.

    Measured: Baseline, every 8 weeks (Breast cancer patients) from start of treatment until first documented disease progression up to 2 years

  4. Dose expansion: Progression free survival

    Progression-free survival is defined as the time from start date of study treatment until objective tumor progression or death from any cause

    Measured: Baseline, every 6 weeks (head-and-neck squamous cell carcinoma (HNSCC) patients) or every 8 weeks (Breast cancer patients) from start of treatment until first documented disease progression up to 2 years

  5. Dose expansion: Overall response rate

    Overall response rate is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR), based on RECIST 1.1 criteria and the investigator assessment.

    Measured: Baseline, every 6 weeks (HNSCC patients) or every 8 weeks (Breast cancer patients) from start of treatment until first documented disease progression up to 2 years

  6. Dose expansion : Duration of Response

    Duration of response is defined as the time of first occurrence of CR or PR until the date of the first documented disease progression or death due to the disease.

    Measured: Baseline, every 6 weeks (HNSCC patients) or every 8 weeks (breast cancer patients) from start of treatment until first documented disease progression up to 2 years

  7. Dose expansion: Plasma pharmacokinetics of BYL719 given in combination with paclitaxel in breast cancer and HNSCC patients

    Plasma concentration time profiles of BYL719 and appropriate individual PK parameters.

    Measured: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 15, and Day 1 of each subsequent Cycle

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2014 (estimated)
  2. Study start5 Mar 2014
  3. Primary completion19 Aug 2016
  4. Study completion19 Aug 2016

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02051751
Sponsor's protocol ID
CBYL719Z2101
Status last verified
Dec 2020
First submitted
21 Jan 2014
Last updated
8 Dec 2020
Results posted
No
Data monitoring committee
No

Publications

  • Rodon J, Curigliano G, Delord JP, Harb W, Azaro A, Han Y, Wilke C, Donnet V, Sellami D, Beck T. A Phase Ib, open-label, dose-finding study of alpelisib in combination with paclitaxel in patients with advanced solid tumors. Oncotarget. 2018 Aug 3;9(60):31709-31718. doi: 10.18632/oncotarget.25854. eCollection 2018 Aug 3.

    PubMed 30167089

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BYL719 and Paclitaxel in people with Neoplasms, Breast Neoplasms, Head and Neck Neoplasms, run by Novartis Pharmaceuticals at 5 sites in 4 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 34 inclusion and 0 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 8 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 5 sites in United States, France, Italy, Spain. 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?

Dose escalation : Dose Limiting Toxicity (DLT) (time frame: Cycle 1 (28 days)). 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?

On the ClinicalTrials.gov record for NCT02051751, which also lists 1 linked publication.

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 8 Dec 2020.

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