HNSCC
Conditions
Keywords
Head and Neck Squamous Cell Carcinoma, Notch 1 loss of function mutation, PI3K/mTOR Inhibitor, Refractory metastatic
Brief 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). 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).
Interventions
DRUGBimiralisib
Bimiralisib capsules
Sponsors
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Oral administration
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytological confirmed diagnosis of Head and Neck Squameous Cell Carcinoma, for which no standard curative or life prolonging therapy is available 2. 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) 3. ECOG performance status of ≤ 2 4. Adequate bone marrow, liver, and renal functions 5. Measurable disease according to RECIST version 1.1 6. Patients of reproductive potential must agree to use effective contraception from screening until 90 days after discontinuing study treatment.
Exclusion criteria
1. Has received any anti-cancer treatment including hormonal and investigational agents within 21 days prior to first dose of bimiralisib. 2. 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. 3. Pregnant or nursing (lactating) women. 4. Poorly controlled diabetes mellitus, steroid-induced diabetes mellitus 5. Has other active malignancies that require systemic treatment. 6. Has a known history of HIV infection 7. 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 8. Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug. 9. Patient has a history of non-compliance to medical regimen or inability to grant consent. 10. 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 11. History of interstitial pneumonitis or patients who require chronic oxygen supplementation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bimiralisib Treatment Bimiralisib capsules (140 mg) orally once daily on 2 consecutive days followed by 5 days without treatment weekly. | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | Bimiralisib Treatment |
|---|---|
| Age, Continuous | 65.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 8 |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 5 / 8 |
Outcome results
Primary
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
Time frame: At 6 and 12 weeks after the start of therapy (± 3 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Single Arm | Objective Response Rate (ORR) | 1 Participants |
Comparison: The primary endpoint was to determine the objective response rate of patients with R/M HNSCC harboring NOTCH1 LOF mutations to oral bimiralisib using RECIST v1.1. We used a Simon's optimal two-stage design. In order to have 80% power to detect a response rate of 30%, (one-sided α=0.05 and β=0.20), we planned to enroll up to 10 patients in the first stage. If ≥ 2 patients had an objective response, then the study would enroll an additional 19 patients in the second stage.95% CI: [1, 58]