HNSCCPhase 2HNSCCNCT03740100
Single-arm Study With Bimiralisib in Patients With HNSCC Harboring NOTCH1 Loss of Function Mutations
A Phase 2 study testing Bimiralisib in people with HNSCC, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
Preclinical data and limited clinical evidence suggest that Head and Neck Squameous Cell Carcinoma tumors harboring certain mutations may respond well to PI3K/mTOR inhibition (phosphatidylinositol-3-kinase/ mammalian target of rapamycin inhibition). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HNSCC
- What is being tested?
- Bimiralisib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Jan 2019to 9 Dec 2020
- Phase
- Phase 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
- Histologically or cytological confirmed diagnosis of Head and Neck Squameous Cell Carcinoma, for which no standard curative or life prolonging therapy is available
- Available CLIA-certified sequencing results of the NOTCH gene in Head and Neck Squameous Cell Carcinoma (HNSCC) tumor material. The tumor must harbor a NOTCH1 LOF mutation as confirmed by central review (MD Anderson Cancer Center, MDACC)
- ECOG performance status of ≤ 2
- Adequate bone marrow, liver, and renal functions
- Measurable disease according to RECIST version 1.1
- Patients of reproductive potential must agree to use effective contraception from screening until 90 days after discontinuing study treatment.
Who cannot join
- Has received any anti-cancer treatment including hormonal and investigational agents within 21 days prior to first dose of bimiralisib.
- Major surgery within 28 days prior to first dose of bimiralisib or persisting side effects that have not improved to NCI-CTCAE grade 1 or better.
- Pregnant or nursing (lactating) women.
- Poorly controlled diabetes mellitus, steroid-induced diabetes mellitus
- Has other active malignancies that require systemic treatment.
- Has a known history of HIV infection
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- Any of the following cardiac abnormalities:
- History of, or current, documented congestive heart failure (New York heart association functional classification iii - iv), documented cardiomyopathy
- Symptomatic (NYHA class II or higher) left ventricular ejection fraction (LVEF) < 40% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (echo)
- Myocardial infarction ≤ 6 months prior to enrolment
- Unstable angina pectoris
- Serious uncontrolled cardiac arrhythmia
- Symptomatic pericarditis
- Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug.
- Patient has a history of non-compliance to medical regimen or inability to grant consent.
- Medically documented history of an active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) or ≥ CTCAE grade 3 anxiety
- History of interstitial pneumonitis or patients who require chronic oxygen supplementation.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Open-label, Single Arm, Two-stage Study, Evaluating the Efficacy and Safety of Bimiralisib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinomas (HNSCC) Harboring NOTCH1 Loss of Function (LOF) Mutations
Preclinical data and limited clinical evidence suggest that Head and Neck Squameous Cell Carcinoma tumors harboring certain mutations may respond well to PI3K/mTOR inhibition (phosphatidylinositol-3-kinase/ mammalian target of rapamycin inhibition).
The current study enrolls patients with refractory and / or metastatic Head and Neck Squameous Cell Carcinoma based on the mutational status of their disease to assess the response to treatment with bimiralisib, an orally available pan-PI3K/mTOR inhibitor (phosphatidylinositol-3-kinase/ mammalian target of rapamycin inhibitor).
- Conditions
- HNSCC
- Being tested
- Bimiralisib
- Keywords
- Head and Neck Squamous Cell Carcinoma, Notch 1 loss of function mutation, PI3K/mTOR Inhibitor, Refractory metastatic
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BimiralisibDrug
Also called PQR309, PI3K/mTOR inhibitor
Bimiralisib capsules
| Study group | Role | What they receive |
|---|---|---|
| Open single arm | Other | Bimiralisib capsules orally Receives: Drug: Bimiralisib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
Radiological tumor assessments were performed by computed tomography (CT) or magnetic resonance imaging (MRI) according to a standard protocol.
ORR: comprised of all patients who achieved a confirmed partial or a confirmed complete response per RECIST 1.1
Measured: At 6 and 12 weeks after the start of therapy (± 3 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2018
- Study start25 Jan 2019
- Primary completion5 Aug 2020
- Study completion9 Dec 2020
Why it stopped: The trial was closed because the sponsor became insolvent.
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 HNSCCStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Oral administration
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Faye M Johnson, MD,PhD, Principal investigator, MD Anderson Cancer Center Recruiting, Houston, Texas, US 77030
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03740100
- Sponsor's protocol ID
- 2018-1003 (PQR309-009)
- Other IDs
- NCI-2019-02978
- Acronym
- HNSCC
- Status last verified
- Jul 2023
- First submitted
- 1 Nov 2018
- Last updated
- 14 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Johnson FM, Janku F, Gouda MA, Tran HT, Kawedia JD, Schmitz D, Streefkerk H, Lee JJ, Andersen CR, Deng D, Rawal S, Shah PA, El-Naggar AK, Johnson JM, Frederick MJ. Inhibition of the Phosphatidylinositol-3 Kinase Pathway Using Bimiralisib in Loss-of-Function NOTCH1-Mutant Head and Neck Cancer. Oncologist. 2022 Dec 9;27(12):1004-e926. doi: 10.1093/oncolo/oyac185.
PubMed 36124629
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Single Arm, Two-stage Study, Evaluating the Efficacy and Safety of Bimiralisib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinomas (HNSCC) Harboring NOTCH1 Loss of Function (LOF) Mutations
- ClinicalTrials.gov ID
- NCT03740100
- Acronym / sponsor ID
- HNSCC / 2018-1003 (PQR309-009)
- Conditions
- HNSCC
- Keywords
- Head and Neck Squamous Cell Carcinoma, Notch 1 loss of function mutation, PI3K/mTOR Inhibitor, Refractory metastatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial was closed because the sponsor became insolvent.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 25 Jan 2019 (actual)
- Primary completion
- 5 Aug 2020 (actual)
- Study completion
- 9 Dec 2020 (actual)
- First posted
- 14 Nov 2018 (actual)
- Results
- Posted 20 Jan 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Preclinical data and limited clinical evidence suggest that Head and Neck Squameous Cell Carcinoma tumors harboring certain mutations may respond well to PI3K/mTOR inhibition (phosphatidylinositol-3-kinase/ mammalian target of rapamycin inhibition).
The current study enrolls patients with refractory and / or metastatic Head and Neck Squameous Cell Carcinoma based on the mutational status of their disease to assess the response to treatment with bimiralisib, an orally available pan-PI3K/mTOR inhibitor (phosphatidylinositol-3-kinase/ mammalian target of rapamycin inhibitor).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Oral administration
| Arm | Type | Receives |
|---|---|---|
| Open single arm | Other | Drug: BimiralisibBimiralisib capsules orally |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Histologically or cytological confirmed diagnosis of Head and Neck Squameous Cell Carcinoma, for which no standard curative or life prolonging therapy is available
- Available CLIA-certified sequencing results of the NOTCH gene in Head and Neck Squameous Cell Carcinoma (HNSCC) tumor material. The tumor must harbor a NOTCH1 LOF mutation as confirmed by central review (MD Anderson Cancer Center, MDACC)
- ECOG performance status of ≤ 2
- Adequate bone marrow, liver, and renal functions
- Measurable disease according to RECIST version 1.1
Key exclusion criteria (17 listed)
- Has received any anti-cancer treatment including hormonal and investigational agents within 21 days prior to first dose of bimiralisib.
- Major surgery within 28 days prior to first dose of bimiralisib or persisting side effects that have not improved to NCI-CTCAE grade 1 or better.
- Pregnant or nursing (lactating) women.
- Poorly controlled diabetes mellitus, steroid-induced diabetes mellitus
- Has other active malignancies that require systemic treatment.
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 |
|---|---|---|
| BimiralisibAlso: PQR309, PI3K/mTOR inhibitorBimiralisib capsules | Drug | Open single arm |
Primary outcome
Objective Response Rate (ORR)
Time frame: At 6 and 12 weeks after the start of therapy (± 3 days)
Radiological tumor assessments were performed by computed tomography (CT) or magnetic resonance imaging (MRI) according to a standard protocol. ORR: comprised of all patients who achieved a confirmed partial or a confirmed complete response per RECIST 1.1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36124629Johnson FM, Janku F, Gouda MA, Tran HT, Kawedia JD, Schmitz D, Streefkerk H, Lee JJ, Andersen CR, Deng D, Rawal S, Shah PA, El-Naggar AK, Johnson JM, Frederick MJ. Inhibition of the Phosphatidylinositol-3 Kinase Pathway Using Bimiralisib in Loss-of-Function NOTCH1-Mutant Head and Neck Cancer. Oncologist. 2022 Dec 9;27(12):1004-e926. doi: 10.1093/oncolo/oyac185.
- M D Anderson Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Faye M Johnson, MD,PhD principal investigator
MD Anderson Cancer Center Recruiting, Houston, Texas, US 77030
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bimiralisib in people with HNSCC, run by M.D. Anderson Cancer Center at 1 site in United States.
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 6 inclusion and 17 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 14 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 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 20 Jan 2022). 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?
Objective Response Rate (ORR) (time frame: At 6 and 12 weeks after the start of therapy (± 3 days)). 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 NCT03740100, 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 14 Jul 2023.