Recurrent Head and Neck Squamous Cell CarcinomaPhase 1/2NCT01602315
A Phase Ib/II Study of BYL719 and Cetuximab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
A Phase 1/2 study testing BYL719 as film-coated (FC) whole tablets, BYL719 as dispersible tablets (DT) and cetuximab in people with Recurrent Head and Neck Squamous Cell Carcinoma and Metastatic Head and Neck Squamous Cell Carcinoma, run by Novartis Pharmaceuticals at 29 sites in 9 countries.
Trial summary
This was a multi-center, open-label, Phase Ib dose escalation /Phase II study in recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) patients considered to be resistant, ineligible or intolerant to platinum-based chemotherapy. The Phase Ib included three arms. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Head and Neck Squamous Cell Carcinoma, Metastatic Head and Neck Squamous Cell Carcinoma
- What is being tested?
- BYL719 as film-coated (FC) whole tablets, BYL719 as dispersible tablets (DT) and cetuximab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 179 participants
- Where
- 29 sitesin 9 countries
- Study dates
- 12 Nov 2012to 16 Sep 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Age ≥ 18 years
- 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.
Show all 13Show fewer
- 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.
Who cannot join
- Prior treatment with PI3K-inhibitors
- 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
Trial locations and contacts
29 sites in 9 countries.
29 sites in 9 countries
United States14 sites
Novartis Investigative Site
Atlanta, Georgia, 30322
Novartis Investigative Site
Aurora, Colorado, 80045
Novartis Investigative Site
Boston, Massachusetts, 02114
Novartis Investigative Site
Charleston, South Carolina, 29425
Novartis Investigative Site
Houston, Texas, 77030
Novartis Investigative Site
Jacksonville, Florida, 32224
Novartis Investigative Site
Nashville, Tennessee, 37232
Novartis Investigative Site
New York, New York, 10017
Novartis Investigative Site
New York, New York, 10029
Novartis Investigative Site
Orlando, Florida, 32806
Novartis Investigative Site
Philadelphia, Pennsylvania, 19104
Novartis Investigative Site
Sacramento, California, 95817
Novartis Investigative Site
San Francisco, California, 94101
Novartis Investigative Site
St Louis, Missouri, 63110
South Korea3 sites
Novartis Investigative Site
Seoul, Korea, 03080
Novartis Investigative Site
Seoul, Korea, 06351
Novartis Investigative Site
Seoul, 03722
Taiwan3 sites
Novartis Investigative Site
Kuei-Shan Chiang, Taoyuan/ Taiwan ROC, 33305
Novartis Investigative Site
Tainan, Taiwan ROC, 70421
Novartis Investigative Site
Taipei, 10048
Australia2 sites
Novartis Investigative Site
Melbourne, Victoria, 3000
Novartis Investigative Site
Murdoch, Western Australia, 6150
France2 sites
Novartis Investigative Site
Lyon, 69373
Novartis Investigative Site
Toulouse, 31059
Netherlands2 sites
Novartis Investigative Site
Maastricht, 5800
Novartis Investigative Site
Nijmegen, 6500 HB
Hong Kong1 site
Novartis Investigative Site
Shatin, New Territories, Hong Kong
About this study
Official title: A Phase Ib Dose Escalation/Randomized Phase II, Multicenter, Open-label Study of BYL719 in Combination With Cetuximab in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
This was a multi-center, open-label, Phase Ib dose escalation /Phase II study in recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) patients considered to be resistant, ineligible or intolerant to platinum-based chemotherapy. The Phase Ib included three arms. Three different methods of administration and two different BYL719 formulations were studied to determine the MTD and/or RP2D of BYL719 in combination with cetuximab:
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.
Read more
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.
- Conditions
- Recurrent Head and Neck Squamous Cell Carcinoma, Metastatic Head and Neck Squamous Cell Carcinoma
- Being tested
- BYL719 as film-coated (FC) whole tablets, BYL719 as dispersible tablets (DT), cetuximab, BYL719 drink suspension
- Keywords
- BYL719, PI3K inhibitor, PIK3CA, cetuximab, EGFR, HNSCC, RM HNSCC, platinum-based chemotherapy, (RM HNSCC) patients, resistant or ineligible/intolerant to platinum-based chemotherapy, swallowing dysfunction, G-tube, alpelisib
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Hereditary Sensory and Autonomic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BYL719 as film-coated (FC) whole tabletsDrug
Also called NVP-BYL719, alpelisib
Oral alpha-specific PI3K inhibitor
BYL719 as dispersible tablets (DT)Drug
Also called NVP-BYL719
New formulation of the oral alpha-specific PI3K inhibitor
cetuximabBiological
Also called erbitux
Recombinant chimeric monoclonal antibody driven against EGFR
BYL719 drink suspensionDrug
Also called NVP-BYL719
Oral alpha-specific PI3K inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Phase Ib: A-BYL719 FC whole tab+cetux | Experimental | Oral film-coated tablets without swallowing dysfunction. Receives: Drug: BYL719 as film-coated (FC) whole tablets; Biological: cetuximab |
| Phase II: 2-Cetuximab | Experimental | Cetuximab in patients naive to cetuximab (phase ll) Receives: Biological: cetuximab |
| Phase Ib: B-BYL719 FC drink sus+cetux | Experimental | Crushed film-coated (FC) tablets as an oral suspension with swallowing dysfunction. Receives: Biological: cetuximab; Drug: BYL719 drink suspension |
| Phase II: 3-BYL719 + Cetuximab | Experimental | 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 Receives: Drug: BYL719 as film-coated (FC) whole tablets; Biological: cetuximab; Drug: BYL719 drink suspension |
| Phase II: 1-BYL719 + Cetuximab | Experimental | 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 Receives: Drug: BYL719 as film-coated (FC) whole tablets; Biological: cetuximab; Drug: BYL719 drink suspension |
| Phase Ib: C-BYL719 DT+cetux | Experimental | Dispersible tablet with swallowing dysfunction administered via a gastrostomy tube (G-tube) Receives: Drug: BYL719 as dispersible tablets (DT); Biological: cetuximab |
| Phase II: Cross over | Experimental | patients received BYL719 at RP2D in combination with cetuximab. Receives: Drug: BYL719 as film-coated (FC) whole tablets; Biological: cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase Ib Arms A: Probability That Dose Limiting Toxicities (DLTs) Rate is in the Recommended Phase 2 Dose in Cycle 1 (Cycle 1=28 Days)
Maximum Tolerated Doses (MTDs) and/or recommended Phase II doses (RP2Ds) of BYL719 in combination with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) in arm A (BYL719 administered as a whole tablet in patients able to swallow the tablets). Dose recommendation was based on posterior summaries including the mean, median, standard deviation, 95%-credibility interval, and the probability that the true DLT rate for each dose combination lies in one of the following categories: (0%, 16%) under-dosing; (16%, 35%) targeted toxicity; (35%, 100%) excessive toxicity. The combination treatment was considered superior to cetuximab alone if the posterior probability (HR > 1) < 10%, and the posterior median HR < 0.7.
Measured: until disease progression or intolerable toxicity (approximately 6 months)
Phase Ib Arm B: Probability That Distribution of Dose Limiting Toxicities (DLTs) is in the Recommended Phase 2 Dose in Cycle 1 (Cycle 1=28 Days)
Maximum Tolerated Doses (MTDs) and/or recommended Phase II doses (RP2Ds) of BYL719 in combination with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) in arm B (crushed film-coated tablets as an oral suspension with swallowing dysfunction). Dose recommendation was based on posterior summaries including the mean, median, standard deviation, 95%-credibility interval, and the probability that the true DLT rate for each dose combination lies in one of the following categories: (0%, 16%) under-dosing; (16%, 35%) targeted toxicity; (35%, 100%) excessive toxicity. The combination treatment was considered superior to cetuximab alone if the posterior probability (HR > 1) < 10%, and the posterior median HR < 0.7.
Measured: until disease progression or intolerable toxicity (approximately 6 months)
For Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 (28 Days)
Estimation of Maximum Tolerated Doses (MTDs) and/or recommended Phase II doses (RP2Ds) of BYL719 in combination with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) in arm A (BYL719 administered as a whole tablet in patients able to swallow the tablets) and arm B (BYL719 administered as a drinkable suspension in patients with swallowing dysfunction).
6 months is an approximate timeframe.
Measured: until disease progression or intolerable toxicity (approximately 6 months)
Phase II Arms 1 and 2: Progression Free Survival (PFS) as Per RECIST v1.1 by Central Radiology Review
Assessment of the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients naive to cetuximab.
6 months is an approximate timeframe.
Measured: approximately 6 months
Phase II Arm 3: Progression Free Survival (PFS) as Per RECIST V1.1
Assessment of the anti-tumor activity of BYL719 in combination with cetuximab in patients resistant to platinum-based therapy and cetuximab.
Measured: approximately 6 months
Phase Ib: Area Under Curve (AUC) 0-24 for BYL719 by Treatment
Comparison of single-dose exposure of BYL719 dispersible tablet via G-tube in combination with cetuximab in RM HNSCC to that of Arm A (film-coated tables)
Measured: 6 months
Secondary outcomes (22)
Phase II: Progression Free Survival (PFS) as Per RECIST v 1.1
Phase II, Scheme 1 (Arm 2B): To further assess the anti-tumor activity of BYL719 + cetuximab in the setting of resistance to single agent cetuximab
Measured: approximately 6 months
Phase Ib: Progression Free Survival (PFS) as Per RECIST v1.1
Assessment of the preliminary anti-tumor activity of BYL719 in combination with cetuximab in arm A, B and C.
Measured: approximately 6 months
Phase II: Randomized Best Overall Response as Per RECIST v1.1
Scheme 1 (Arms 1 and 2): Further assessment of the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients naive to cetuximab
Measured: approximately 6 months
Phase II: Non-Randomized Best Overall Response as Per RECIST v1.1
Scheme 1 (Arm 3): Further assessment of the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients naive to cetuximab
Measured: approximately 6 months
Phase II: Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1
Assessment of the preliminary anti-tumor activity of BYL719 in combination with cetuximab in arms 1 and 2.
Measured: approximately 6 months
Phase II: Non-Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1
Scheme 1 (arm 3): Assessment of the preliminary anti-tumor activity of BYL719 in combination with cetuximab in arm 3 (non-randomized arm)
Measured: approximately 6 months
Phase II: Randomized Overall Survival (OS) by Treatment
Scheme 1 (Arms 1 and 2): Further assessment of the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients naive to cetuximab
Measured: approximately 1 year
Phase II: Non-Randomized Overall Survival (OS) by Treatment
Scheme 1 (Arm 3): Further assessment of the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients naive to cetuximab
Measured: approximately 1 year
For Phase Ib: Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1
Assessment of the preliminary anti-tumor activity of BYL719 in combination with cetuximab in arm A, B and C
CR=complete response PR=partial response
Measured: approximately 6 months
Phase II, Scheme 1 (Arm 2B): Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1
Phase II: Scheme 1 (Arm 2B): To further assess the anti-tumor activity of BYL719 + cetuximab in the setting of resistance to single agent cetuximab.
Complete response (CR); Partial response (PR); Stable disease (SD)
Measured: Approximately 6 months
Phase II, Scheme 2 (Arm 2B): Overall Survival (OS) for the Cross-over
Phase II, Scheme 1 (Arm 2B): To further assess the anti-tumor activity of BYL719 + cetuximab in the setting of resistance to single agent cetuximab.
Measured: approximately 1 year
Phase Ib: Primary Plasma Pharmacokinetic Parameters for BYL719 by Treatment
Non compartmental PK parameters derived after single dose at Cycle 1 Day 1
Measured: 1 to 24 hours post dose (Day 1 Cycle 1)
Phase Ib: Cmax for BYL719 by Treatment
Non compartmental Cmax derived after single dose at Cycle 1 Day 1
Measured: Day 1 Cycle 1
Phase Ib: Tmax for BYL719 by Treatment
Non compartmental Cmax derived after single dose at Cycle 1 Day 1
Measured: Day 1 Cycle 1
Phase Ib: Plasma Pharmacokinetic Parameters for BYL719 After Continuous Dose Administration (Steady State)
Non compartmental PK parameters derived after single dose at Cycle 1 Day 1
Measured: Day 1 Cycle 1
Phase Ib: Cmax for BYL719 After Continuous Dose Administration (Steady State)
Non compartmental PK parameters derived after single dose at Cycle 1 Day 1
Measured: Day 1 Cycle 1
Phase Ib: Tmax for BYL719 After Continuous Dose Administration (Steady State)
Non compartmental PK parameters derived after single dose at Cycle 1 Day 1
Measured: Day 1 Cycle 1
Phase Ib: Notable Abnormal Vital Signs by Treatment
Characterization of the safety and tolerability of BYL719 in combination with cetuximab in arm A, B and C.
Measured: approximately 6 months
Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities
Characterization of the safety and tolerability of BYL719 in combination with cetuximab in arm A, B and C.
Measured: baseline, post baseline
For Phase II: Notable Abnormal Vital Signs by Treatment
Characterization of the safety and tolerability of BYL719 in combination with cetuximab in arm 1, 2 and 2B.
Measured: approximately 6 months
For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities
Characterization of the safety and tolerability of BYL719 in combination with cetuximab in arm 1, 2 and 2B.
Measured: baseline, post baseline during the entire study period (approximately 1 year)
Phase II: Progression Free Survival (PFS) Based on Investigator's Assessment With Treatment
Assessment of the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients naive to cetuximab
Measured: approximately 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2012 (estimated)
- Study start12 Nov 2012
- Primary completion16 Sep 2016
- Study completion16 Sep 2016
Why it stopped: early termination due to Sponsor decision (slow recruitment)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 179 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01602315
- Sponsor's protocol ID
- CBYL719X2104
- Other IDs
- 2011-006017-34
- Status last verified
- Apr 2018
- First submitted
- 16 May 2012
- Last updated
- 29 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37875771
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Dose Escalation/Randomized Phase II, Multicenter, Open-label Study of BYL719 in Combination With Cetuximab in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT01602315
- Acronym / sponsor ID
- CBYL719X2104
- Conditions
- Recurrent Head and Neck Squamous Cell Carcinoma, Metastatic Head and Neck Squamous Cell Carcinoma
- Keywords
- BYL719, PI3K inhibitor, PIK3CA, cetuximab, EGFR, HNSCC, RM HNSCC, platinum-based chemotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: early termination due to Sponsor decision (slow recruitment)
- Enrolment
- 179 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 12 Nov 2012 (actual)
- Primary completion
- 16 Sep 2016 (actual)
- Study completion
- 16 Sep 2016 (actual)
- First posted
- 18 May 2012 (estimated)
- Results
- Posted 21 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a multi-center, open-label, Phase Ib dose escalation /Phase II study in recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) patients considered to be resistant, ineligible or intolerant to platinum-based chemotherapy. The Phase Ib included three arms. Three different methods of administration and two different BYL719 formulations were studied to determine the MTD and/or RP2D of BYL719 in combination with cetuximab:
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Phase Ib: A-BYL719 FC whole tab+cetux | Experimental | Drug: BYL719 as film-coated (FC) whole tablets, Biological: cetuximabOral film-coated tablets without swallowing dysfunction. |
| Phase II: 2-Cetuximab | Experimental | Biological: cetuximabCetuximab in patients naive to cetuximab (phase ll) |
| Phase Ib: B-BYL719 FC drink sus+cetux | Experimental | Biological: cetuximab, Drug: BYL719 drink suspensionCrushed film-coated (FC) tablets as an oral suspension with swallowing dysfunction. |
| Phase II: 3-BYL719 + Cetuximab | Experimental | Drug: BYL719 as film-coated (FC) whole tablets, Biological: cetuximab, Drug: BYL719 drink suspensionBYL719 + 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 |
| Phase II: 1-BYL719 + Cetuximab | Experimental | Drug: BYL719 as film-coated (FC) whole tablets, Biological: cetuximab, Drug: BYL719 drink suspensionBYL719 + 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 |
| Phase Ib: C-BYL719 DT+cetux | Experimental | Drug: BYL719 as dispersible tablets (DT), Biological: cetuximabDispersible tablet with swallowing dysfunction administered via a gastrostomy tube (G-tube) |
| Phase II: Cross over | Experimental | Drug: BYL719 as film-coated (FC) whole tablets, Biological: cetuximabpatients received BYL719 at RP2D in combination with cetuximab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Age ≥ 18 years
- 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
Key exclusion criteria (8 listed)
- Prior treatment with PI3K-inhibitors
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BYL719 as film-coated (FC) whole tabletsAlso: NVP-BYL719, alpelisibOral alpha-specific PI3K inhibitor | Drug | Phase II: 1-BYL719 + Cetuximab, Phase II: 3-BYL719 + Cetuximab, Phase II: Cross over, Phase Ib: A-BYL719 FC whole tab+cetux |
| BYL719 as dispersible tablets (DT)Also: NVP-BYL719New formulation of the oral alpha-specific PI3K inhibitor | Drug | Phase Ib: C-BYL719 DT+cetux |
| cetuximabAlso: erbituxRecombinant chimeric monoclonal antibody driven against EGFR | Biological | Phase II: 1-BYL719 + Cetuximab, Phase II: 2-Cetuximab, Phase II: 3-BYL719 + Cetuximab, Phase II: Cross over, Phase Ib: A-BYL719 FC whole tab+cetux, Phase Ib: B-BYL719 FC drink sus+cetux, Phase Ib: C-BYL719 DT+cetux |
| BYL719 drink suspensionAlso: NVP-BYL719Oral alpha-specific PI3K inhibitor | Drug | Phase II: 1-BYL719 + Cetuximab, Phase II: 3-BYL719 + Cetuximab, Phase Ib: B-BYL719 FC drink sus+cetux |
Primary outcome
Phase Ib Arms A: Probability That Dose Limiting Toxicities (DLTs) Rate is in the Recommended Phase 2 Dose in Cycle 1 (Cycle 1=28 Days)
Time frame: until disease progression or intolerable toxicity (approximately 6 months)
Maximum Tolerated Doses (MTDs) and/or recommended Phase II doses (RP2Ds) of BYL719 in combination with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) in arm A (BYL719 administered as a whole tablet in patients able to swallow the tablets). Dose recommendation was based on posterior summaries including the mean, median, standard deviation, 95%-credibility interval, and the probability that the true DLT rate for each dose combination lies in one of the following categories: (0%, 16%) under-dosing; (16%, 35%) targeted toxicity; (35%, 100%) excessive toxicity. The combination treatment was considered superior to cetuximab alone if the posterior probability (HR > 1) < 10%, and the posterior median HR < 0.7.
Phase Ib Arm B: Probability That Distribution of Dose Limiting Toxicities (DLTs) is in the Recommended Phase 2 Dose in Cycle 1 (Cycle 1=28 Days)
Time frame: until disease progression or intolerable toxicity (approximately 6 months)
Maximum Tolerated Doses (MTDs) and/or recommended Phase II doses (RP2Ds) of BYL719 in combination with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) in arm B (crushed film-coated tablets as an oral suspension with swallowing dysfunction). Dose recommendation was based on posterior summaries including the mean, median, standard deviation, 95%-credibility interval, and the probability that the true DLT rate for each dose combination lies in one of the following categories: (0%, 16%) under-dosing; (16%, 35%) targeted toxicity; (35%, 100%) excessive toxicity. The combination treatment was considered superior to cetuximab alone if the posterior probability (HR > 1) < 10%, and the posterior median HR < 0.7.
For Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 (28 Days)
Time frame: until disease progression or intolerable toxicity (approximately 6 months)
Estimation of Maximum Tolerated Doses (MTDs) and/or recommended Phase II doses (RP2Ds) of BYL719 in combination with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) in arm A (BYL719 administered as a whole tablet in patients able to swallow the tablets) and arm B (BYL719 administered as a drinkable suspension in patients with swallowing dysfunction). 6 months is an approximate timeframe.
Phase II Arms 1 and 2: Progression Free Survival (PFS) as Per RECIST v1.1 by Central Radiology Review
Time frame: approximately 6 months
Assessment of the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients naive to cetuximab. 6 months is an approximate timeframe.
Phase II Arm 3: Progression Free Survival (PFS) as Per RECIST V1.1
Time frame: approximately 6 months
Assessment of the anti-tumor activity of BYL719 in combination with cetuximab in patients resistant to platinum-based therapy and cetuximab.
Phase Ib: Area Under Curve (AUC) 0-24 for BYL719 by Treatment
Time frame: 6 months
Comparison of single-dose exposure of BYL719 dispersible tablet via G-tube in combination with cetuximab in RM HNSCC to that of Arm A (film-coated tables)
22 secondary outcomes
Phase II: Progression Free Survival (PFS) as Per RECIST v 1.1
Time frame: approximately 6 months
Phase Ib: Progression Free Survival (PFS) as Per RECIST v1.1
Time frame: approximately 6 months
Phase II: Randomized Best Overall Response as Per RECIST v1.1
Time frame: approximately 6 months
Phase II: Non-Randomized Best Overall Response as Per RECIST v1.1
Time frame: approximately 6 months
Phase II: Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1
Time frame: approximately 6 months
Phase II: Non-Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1
Time frame: approximately 6 months
Phase II: Randomized Overall Survival (OS) by Treatment
Time frame: approximately 1 year
Phase II: Non-Randomized Overall Survival (OS) by Treatment
Time frame: approximately 1 year
For Phase Ib: Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1
Time frame: approximately 6 months
Phase II, Scheme 1 (Arm 2B): Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1
Time frame: Approximately 6 months
Phase II, Scheme 2 (Arm 2B): Overall Survival (OS) for the Cross-over
Time frame: approximately 1 year
Phase Ib: Primary Plasma Pharmacokinetic Parameters for BYL719 by Treatment
Time frame: 1 to 24 hours post dose (Day 1 Cycle 1)
Phase Ib: Cmax for BYL719 by Treatment
Time frame: Day 1 Cycle 1
Phase Ib: Tmax for BYL719 by Treatment
Time frame: Day 1 Cycle 1
Phase Ib: Plasma Pharmacokinetic Parameters for BYL719 After Continuous Dose Administration (Steady State)
Time frame: Day 1 Cycle 1
Phase Ib: Cmax for BYL719 After Continuous Dose Administration (Steady State)
Time frame: Day 1 Cycle 1
Phase Ib: Tmax for BYL719 After Continuous Dose Administration (Steady State)
Time frame: Day 1 Cycle 1
Phase Ib: Notable Abnormal Vital Signs by Treatment
Time frame: approximately 6 months
Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities
Time frame: baseline, post baseline
For Phase II: Notable Abnormal Vital Signs by Treatment
Time frame: approximately 6 months
For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities
Time frame: baseline, post baseline during the entire study period (approximately 1 year)
Phase II: Progression Free Survival (PFS) Based on Investigator's Assessment With Treatment
Time frame: approximately 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37875771Razak 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.
- Results for CBYL719X2104 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Recurrent Head and Neck Squamous Cell Carcinoma
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingPhase 3
Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma
RecruitingPhase 1
Autologous CAR-T Cells Targeting CSPG4 in Relapsed/Refractory HNSCC
Head and Neck Cancer, Relapse
RecruitingPhase 1
A Study of LY4052031 in Participants With Advanced or Metastatic Urothelial Cancer or Other Solid Tumors
Metastatic Solid Tumor, Recurrent Solid Tumor
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
29 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BYL719 as film-coated (FC) whole tablets, BYL719 as dispersible tablets (DT) and cetuximab in people with Recurrent Head and Neck Squamous Cell Carcinoma and Metastatic Head and Neck Squamous Cell Carcinoma, run by Novartis Pharmaceuticals at 29 sites in 9 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 13 inclusion and 8 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: stopped early, as of the sponsor's last update on 29 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 29 sites in United States, South Korea, Taiwan, Australia, France and 4 more countries. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Phase Ib Arms A: Probability That Dose Limiting Toxicities (DLTs) Rate is in the Recommended Phase 2 Dose in Cycle 1 (Cycle 1=28 Days) (time frame: until disease progression or intolerable toxicity (approximately 6 months)). The study lists 6 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 NCT01602315, 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 29 Dec 2020.