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PIK3CA Mutated Advanced Solid TumorsPhase 1/2NCT01708161

A Phase Ib/II Study of the Combination of BYL719 Plus AMG 479 in Adult Patients With Selected Solid Tumors

A Phase 1/2 study testing BYL719 and AMG 479 in people with PIK3CA Mutated Advanced Solid Tumors and PIK3CA Amplified Advanced Solid Tumors, run by Novartis Pharmaceuticals at 10 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This was a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part was to estimate the MTD(s) and/or identify the recommended phase II dose(s) (RP2Ds) for the combination of BYL719 and AMG 479 (ganitumab), followed by the phase II part to assess the clinical efficacy and to further assess the safety… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
BYL719 and AMG 479
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
10 sitesin 4 countries
Study dates
27 Nov 2012to 1 Jun 2017
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

  • Written informed consent.
  • Patients aged ≥ 18 years (male or female).
  • Patients with the following histologically/cytologically-confirmed advanced solid tumors with documented somatic PIK3CA mutations or amplifications in tumor tissue:
  • Hormone receptor positive breast carcinoma
  • Ovarian carcinoma
  • Other tumors upon agreement with sponsor
  • Adequate organ function
  • Negative serum pregnancy test

Who cannot join

  • Patients with known history of severe infusion reactions to monoclonal antibodies.
  • Patients with primary CNS tumor or CNS tumor involvement.
  • History of thromboembolic event requiring full-dose anti-coagulation therapy any time prior to enrollment.
  • Clinically significant cardiac disease.
  • History of another malignancy within last 2 years.
  • Pregnant or nursing (lactating) women.

Trial locations and contacts

10 sites in 4 countries.

10 sites in 4 countries

United States4 sites

  • Novartis Investigative Site

    Boston, Massachusetts, 02114

  • Novartis Investigative Site

    Los Angeles, California, 90095

  • Novartis Investigative Site

    Nashville, Tennessee, 37203

  • Novartis Investigative Site

    New York, New York, 10017

Other trials in United States

Spain4 sites

  • Novartis Investigative Site

    Barcelona, Catalonia, 08035

  • Novartis Investigative Site

    Madrid, 28033

  • Novartis Investigative Site

    Madrid, 28041

  • Novartis Investigative Site

    Seville, Andalusia, 41013

Other trials in Spain

Belgium1 site

  • Novartis Investigative Site

    Leuven, 3000

Other trials in Belgium

Canada1 site

  • Novartis Investigative Site

    Toronto, Ontario, M5G 1Z6

Other trials in Canada

About this study

This was a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part was to estimate the MTD(s) and/or identify the recommended phase II dose(s) (RP2Ds) for the combination of BYL719 and AMG 479 (ganitumab), followed by the phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. Patients were to be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. All patients were to be followed up. At a minimum, patients must have completed the safety follow-up assessments 30 days after the last dose of the study treatment.

Read the detailed description

This was a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part was to estimate the MTD(s) and/or identify the recommended phase II dose(s) (RP2Ds) for the combination of BYL719 and AMG 479 (ganitumab), followed by the phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. The dose escalation part of the study were to be guided by a Bayesian Logistic Regression Model (BLRM).

Once MTD/RP2D had been determined, patients were to be enrolled in two Phase II arms. Patients with PIK3CA mutated or amplified hormone receptor positive breast carcinoma were to be enrolled in Arm 1; patients with PIK3CA mutated or amplified ovarian carcinoma were to be enrolled in Arm 2. Patients were to be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. All patients were to be followed up. At a minimum, patients must have completed the safety follow-up assessments 30 days after the last dose of the study treatment.

Being tested
BYL719, AMG 479
Keywords
PIK3CA mutation, advanced solid tumor, breast cancer, ovarian cancer, cancers with a mass, bulky tumor, nodule, lump, advanced cancer, advanced solid malignancies
Medical subject headings
Breast Neoplasms, Ovarian Neoplasms

What participants receive

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

  • BYL719Drug

    Also called ALPELISIB

    BYL719 is a small molecule inhibiting PI3-Kinase.

  • AMG 479Drug

    Also called ganitumab

    AMG 479 is a monoclonal antibody directed against IGF1-R.

Study groups in NCT01708161
Study groupRoleWhat they receive
BYL719 + AMG 479ExperimentalFor: Dose escalation phase/Phase II Expansion Phase. Cohorts of 3-6 patients were to be enrolled sequentially until an MTD or a recommended Phase II dose were defined. All patients were to receive the combination treatment. Sequential cohorts may receive different doses of the combination. In the Phase II expansion, all patients were to receive the same combination treatment.
Receives: Drug: BYL719; Drug: AMG 479

What is being measured

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

  1. Dose Limiting Toxicities (DLTs) - Phase Ib

    Phase lb only

    Measured: 28 days

  2. Percentage of Patients With Overall Response Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II

    The antitumor activity of alpelisib in combination with ganitumab in patients with PIK3CA mutated or amplified hormone receptor positive (HR+) breast (arm 1) or ovarian (arm 2) cancer.

    Overall response rate is defined as the proportion of patients who have a best overall response of complete response or partial response assessed per RECIST 1.1.

    Measured: Approximately 1 year (since initiation of Phase II, Dec 2013, till Primary CSR cut off 06Jan2015)

Secondary outcomes (9)

  1. Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib

    The anti-tumor activity of alpelisib and ganitumab in combination as per RECIST 1.1

    Measured: Approximately 1 year (since FPFV 27Nov2012, till MTD declaration 26Nov2013)

  2. Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment - Phase Ib

    The anti-tumor activity of alpelisib and ganitumab in combination as per RECIST 1.1

    Measured: Approximately 1 year (since FPFV 27Nov2012, till MTD declaration 26Nov2013)

  3. Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II

    the antitumor activity of alpelisib in combination with ganitumab in patients with PIK3CA mutated or amplified hormone receptor positive (HR+) breast (arm 1) or ovarian (arm 2) cancer.

    Phase II only, Cycle 1 Day 1 through Cycle 6 Day 28; assessed at baseline and every 8 weeks thereafter

    Measured: Approximately 1 year (since initiation of Phase II, Dec 2013, till Primary CSR cut off 06Jan2015)

  4. Cmax of BYL - Phase Ib

    Serum concentration for BYL719 (alpelisib)

    1 cycle - 28 days of treatment

    Measured: Cycle 1 Day 1, Cycle 1 Day 15

  5. Area Under Curve (AUC) 0-24 Hour of BYL - Phase Ib

    Area under curve for BYL719 (alpelisib)

    1 cycle - 28 days of treatment

    Measured: Cycle 1 Day 1 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose), Cycle 1 Day 15 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose)

  6. Tmax and T Half of BYL - Phase Ib

    Tmax and half life of BYL719 (Alpelisib)

    1 cycle - 28 days of treatment

    Measured: Cycle 1 Day 1, Cycle 1 Day 15

  7. Cmax of AMG - Phase Ib

    Serum concentration for AMG 479 (ganitumab)

    1 cycle - 28 days of treatment

    Measured: Cycle 1 Day 15

  8. Area Under Curve (AUC) 0-336 Hour of AMG - Phase Ib

    Area under curve for AMG 479 (ganitumab)

    1 cycle - 28 days of treatment

    Measured: Cycle 1 Day 15 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose)

  9. Tmax and T Half of AMG - Phase Ib

    Tmax and half life of AMG 479 (ganitumab)

    1 cycle - 28 days of treatment

    Measured: Cycle 1 Day 15

Timeline

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

  1. First posted16 Oct 2012 (estimated)
  2. Study start27 Nov 2012
  3. Primary completion26 Dec 2014
  4. Study completion1 Jun 2017

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01708161
Sponsor's protocol ID
CBYL719X2105J
Other IDs
2012-001962-13
Status last verified
Aug 2018
First submitted
19 Sep 2012
Last updated
13 Sep 2018
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing BYL719 and AMG 479 in people with PIK3CA Mutated Advanced Solid Tumors and PIK3CA Amplified Advanced Solid Tumors, run by Novartis Pharmaceuticals at 10 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 8 inclusion and 6 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 13 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States, Spain, Belgium, Canada. 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 28 Jun 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?

Dose Limiting Toxicities (DLTs) - Phase Ib (time frame: 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 NCT01708161.

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 13 Sep 2018.

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