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

NCT ID: NCT02051751

Last Updated: 2020-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

19 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-05

Study Completion Date

2016-08-19

Brief Summary

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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

Detailed Description

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Conditions

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Neoplasms, Breast Neoplasms, Head and Neck Neoplasms

Keywords

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Solid tumors, Head and neck non squamous cell carcinoma, breast cancer, PI3K inhibitor, BYL719, paclitaxel

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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BYL719 and paclitaxel

All patients enrolled in the study will receive BYL719 once daily plus weekly paclitaxel

Group Type EXPERIMENTAL

BYL719

Intervention Type DRUG

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.

Paclitaxel

Intervention Type DRUG

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.

Interventions

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BYL719

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.

Intervention Type DRUG

Paclitaxel

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. \- Adult \> or = 18 years old
2. \- has signed the Informed Consent Form (ICF)
3. \- has at least one measurable or non-measurable disease as per RECIST 1.1
4. \- has tumor tissue available for the analysis as described in the protocol
5. \- has adequate bone marrow and organ function as defined in the protocol
6. \- is able to swallow and retain oral medication for the dose escalation part, ALL above PLUS
7. \- 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.
8. \- 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

Exclusion Criteria

1. \- has received previous treatment with a PI3K or AKT inhibitor as described in the protocol
2. \- has a known hypersensitivity to paclitaxel or other products containing Cremophor
3. \- has a contraindication to use the standard pre-treatment for paclitaxel
4. \- has a primary central nervous system (CNS) tumor or CNS tumor involvement as detailed in the protocol
5. \- has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy
6. \- 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
7. \- has peripheral sensory neuropathy with functional impairment (CTC grade 2 neuropathy or higher)
8. \- has undergone major surgery ≤ 4 weeks prior to starting study treatment or who has not recovered from side effects of such procedure
9. \- has a clinically significant cardiac disease or impaired cardiac function as detailed in the protocol
10. \- 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
11. \- has diabetes mellitus requiring insulin treatment and/or with clinical signs
12. \- has impaired gastrointestinal (GI) function or GI disease as described in the protocol
13. \- has a known positive serology for human immunodeficiency virus (HIV), active Hepatitis B, and/or active Hepatitis C infection
14. \- 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
15. \- 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
16. \- is currently receiving treatment with agents that are metabolized solely by CYP3A and/or have a narrow therapeutic window
17. \- 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
18. \- Patient has a history of non-compliance to medical regimen or inability to grant consent
19. \- Pregnant or nursing (lactating) women
20. \- does not apply highly effective contraception during the study and through the duration as defined in the protocol



\- 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Highlands Oncology Group

Fayetteville, Arkansas, United States

Site Status

Horizon Oncology Center BioAdvance

Lafayette, Indiana, United States

Site Status

Novartis Investigative Site

Toulouse, , France

Site Status

Novartis Investigative Site

Milan, MI, Italy

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Countries

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Australia Switzerland United States France Italy Spain

References

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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.

Reference Type DERIVED
PMID: 30167089 (View on PubMed)

Related Links

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Other Identifiers

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CBYL719Z2101

Identifier Type: -

Identifier Source: org_study_id