A Phase Ib/II Study of BYL719 and Cetuximab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
NCT ID: NCT01602315
Last Updated: 2020-12-29
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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TERMINATED
PHASE1/PHASE2
179 participants
INTERVENTIONAL
2012-11-12
2016-09-16
Brief Summary
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Arm A - film-coated whole tablets were orally administered to patients who were able to swallow the tablets; Arm B - a drinkable suspension prepared from crushed film-coated tablets was administered orally to patients with swallowing dysfunction Arm C - a suspension from a dispersible tablet administered via G-tube, in patients with swallowing dysfunction. Arm C was used to investigate the pharmacokinetics (PK), compared to Arm A (film coated tablet), and safety of the dispersible tablet of the dispersible tablet formulation of BYL719.
The Phase II investigated the clinical efficacy of BYL719 and consisted of an open label, randomized Phase II part investigating BYL719 in combination with cetuximab compared to cetuximab alone in patients resistant or intolerant to platinum and naïve to cetuximab (Scheme 1: Arm 1 and Arm 2), and a non-randomized Phase II part Scheme 2: Arm 3. In addition, patients who experienced disease progression in Arm 2 (cetuximab) were allowed to switch to the combination regimen (cross-over, Arm 2B). The safety of the BYL719 in combination with cetuximab was also further characterized in Arms 1, 2B and 3.
Patients were treated until progression of disease), unacceptable toxicity, or withdrawal of informed consent, whichever occurred first (except for phase II Arm 2 had the opportunity to crossover to the combination treatment (Arm 2B). In the follow-up period all patients had to complete the safety follow-up assessments within 30 days after the last dose of the study treatment. Patients who did not have disease progression at the time of discontinuation of study treatment were radiologically followed for disease status until disease progression, initiation of subsequent anticancer therapies, or death, whichever occurred first. In addition, all patients enrolled in Phase II were followed for survival.
Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Phase Ib: A-BYL719 FC whole tab+cetux
Oral film-coated tablets without swallowing dysfunction.
BYL719 as film-coated (FC) whole tablets
Oral alpha-specific PI3K inhibitor
cetuximab
Recombinant chimeric monoclonal antibody driven against EGFR
Phase II: 2-Cetuximab
Cetuximab in patients naive to cetuximab (phase ll)
cetuximab
Recombinant chimeric monoclonal antibody driven against EGFR
Phase Ib: B-BYL719 FC drink sus+cetux
Crushed film-coated (FC) tablets as an oral suspension with swallowing dysfunction.
cetuximab
Recombinant chimeric monoclonal antibody driven against EGFR
BYL719 drink suspension
Oral alpha-specific PI3K inhibitor
Phase II: 3-BYL719 + Cetuximab
BYL719 + cetuximab in patients resistant to cetuximab. BYL719 can be administered as FC whole/crushed only or DT via G-tube in addition, depending on the Phase Ib results
BYL719 as film-coated (FC) whole tablets
Oral alpha-specific PI3K inhibitor
cetuximab
Recombinant chimeric monoclonal antibody driven against EGFR
BYL719 drink suspension
Oral alpha-specific PI3K inhibitor
Phase II: 1-BYL719 + Cetuximab
BYL719 + Cetuximab in Patients naive to cetuximab. BYL719 can be administered as FC whole/crushed only or DT via G-tube in addition, depending on the Phase Ib results
BYL719 as film-coated (FC) whole tablets
Oral alpha-specific PI3K inhibitor
cetuximab
Recombinant chimeric monoclonal antibody driven against EGFR
BYL719 drink suspension
Oral alpha-specific PI3K inhibitor
Phase Ib: C-BYL719 DT+cetux
Dispersible tablet with swallowing dysfunction administered via a gastrostomy tube (G-tube)
BYL719 as dispersible tablets (DT)
New formulation of the oral alpha-specific PI3K inhibitor
cetuximab
Recombinant chimeric monoclonal antibody driven against EGFR
Phase II: Cross over
patients received BYL719 at RP2D in combination with cetuximab.
BYL719 as film-coated (FC) whole tablets
Oral alpha-specific PI3K inhibitor
cetuximab
Recombinant chimeric monoclonal antibody driven against EGFR
Interventions
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BYL719 as film-coated (FC) whole tablets
Oral alpha-specific PI3K inhibitor
BYL719 as dispersible tablets (DT)
New formulation of the oral alpha-specific PI3K inhibitor
cetuximab
Recombinant chimeric monoclonal antibody driven against EGFR
BYL719 drink suspension
Oral alpha-specific PI3K inhibitor
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Patients with histologically/cytologically-confirmed HNSCC
* Patients must be resistant to platinum-based chemotherapy, or be ineligible (due to medical comorbidities) or intolerant to platinum-based therapy per medical history
* For Phase Ib, there is no restriction on the number of prior therapies for recurrent or metastatic disease
* For Phase II, patients may have received a maximum of 1 prior line of therapy for recurrent or metastatic disease
* For Phase Ib, prior cetuximab or other EGFR-targeted antibody therapy is allowed regardless of the prior treatment settings.
* For Phase II, Arms 1 and 2, prior cetuximab or other EGFR-targeted antibody therapy is allowed only if administered in the induction setting, or concurrently with radiation in the curative setting, with the last dose of cetuximab administered at least 12 months prior to starting the study treatment. For Arm 3, prior cetuximab must have been administered in the curative, recurrent or metastatic disease setting and disease progression documented within 9 months of the last dose of cetuximab administered in that setting. This regimen (including both platinum and cetuximab) must be the most recent anti-neoplastic treatment regimen administered.
* Patients with swallowing dysfunction who are unable to swallow BYL719 whole tablets and are not using feeding tubes for study drug administration can participate in the Phase Ib Arm B. For the Phase II, these patients with swallowing dysfunction may participate if able to drink the suspension and results of Arm B confirm the use of this method. Patients with swallowing dysfunction requiring G tube (G/PEG tube) for study drug administration may participate in Phase II if Arm C confirms dispersible tablet via G tube administration is permitted if the administration of drinkable suspension of BYL719 is allowed to be used in Phase II.
* Availability of a representative tumor specimen. Patients enrolled in Arm 3 of Phase II must have disease sites amenable to biopsy unless prior agreement between Novartis and the Investigator.
* At least one measurable or non-measurable lesion as per RECIST 1.1 criteria for patients in Phase Ib; Measurable disease as determined by RECIST v1.1 for Phase II patients
* World Health Organization (WHO) Performance Status (PS) ≤ 2
* Adequate organ function
* Negative serum pregnancy test.
Exclusion Criteria
* Patients with a prior serious infusion reaction to cetuximab
* Patients with uncontrolled CNS tumor metastatic involvement
* Clinically significant cardiac disease or impaired cardiac function
* Patients with diabetes mellitus
* Impaired GI function or GI disease
* History of another malignancy within 2 years prior to starting study treatment
* Pregnant or nursing (lactating) women
18 Years
ALL
No
Sponsors
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Novartis Pharmaceuticals
INDUSTRY
Responsible Party
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Principal Investigators
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Novartis Pharmaceuticals
Role: STUDY_DIRECTOR
Novartis Pharmaceuticals
Locations
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Novartis Investigative Site
Sacramento, California, United States
Novartis Investigative Site
San Francisco, California, United States
Novartis Investigative Site
Aurora, Colorado, United States
Novartis Investigative Site
Jacksonville, Florida, United States
Novartis Investigative Site
Orlando, Florida, United States
Novartis Investigative Site
Atlanta, Georgia, United States
Novartis Investigative Site
Boston, Massachusetts, United States
Novartis Investigative Site
St Louis, Missouri, United States
Novartis Investigative Site
New York, New York, United States
Novartis Investigative Site
New York, New York, United States
Novartis Investigative Site
Philadelphia, Pennsylvania, United States
Novartis Investigative Site
Charleston, South Carolina, United States
Novartis Investigative Site
Nashville, Tennessee, United States
Novartis Investigative Site
Houston, Texas, United States
Novartis Investigative Site
Melbourne, Victoria, Australia
Novartis Investigative Site
Murdoch, Western Australia, Australia
Novartis Investigative Site
Toronto, Ontario, Canada
Novartis Investigative Site
Lyon, , France
Novartis Investigative Site
Toulouse, , France
Novartis Investigative Site
Shatin, New Territories, Hong Kong, Hong Kong
Novartis Investigative Site
Maastricht, , Netherlands
Novartis Investigative Site
Nijmegen, , Netherlands
Novartis Investigative Site
Singapore, , Singapore
Novartis Investigative Site
Seoul, Korea, South Korea
Novartis Investigative Site
Seoul, Korea, South Korea
Novartis Investigative Site
Seoul, , South Korea
Novartis Investigative Site
Tainan City, Taiwan ROC, Taiwan
Novartis Investigative Site
Kuei-Shan Chiang, Taoyuan/ Taiwan ROC, Taiwan
Novartis Investigative Site
Taipei, , Taiwan
Countries
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References
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Razak ARA, Wang HM, Chang JY, Ahn MJ, Munster P, Blumenschein G Jr, Solomon B, Lim DW, Hong RL, Pfister D, Saba NF, Lee SH, van Herpen C, Quadt C, Bootle D, Blumenstein L, Demanse D, Delord JP. A Phase 1b/2 Study of Alpelisib in Combination with Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Target Oncol. 2023 Nov;18(6):853-868. doi: 10.1007/s11523-023-00997-z. Epub 2023 Oct 25.
Related Links
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Results for CBYL719X2104 can be found on the Novartis Clinical Trial Results Website
Other Identifiers
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2011-006017-34
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
CBYL719X2104
Identifier Type: -
Identifier Source: org_study_id