Conditions: HNSCC
Keywords: Head and Neck Squamous Cell Carcinoma Notch 1 loss of function mutation PI3K/mTOR Inhibitor Refractory metastatic
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 8
Healthy volunteers: no

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).

Detailed description:

Arms:
arm 1: Bimiralisib capsules orally

Interventions: intervention 1: Bimiralisib
Intervention descriptions: intervention 1: Bimiralisib capsules

Protocol document:
ICF_002.pdf: 



























Prot_000.pdf: 
Study title: 
Single-arm Study With Bimiralisib in Patients With HNSCC Harboring NOTCH1 
Loss of Function Mutations 
 
ClinicalTrials.gov record number: 
NCT03740100 
 
MD Anderson protocol number: 
2018-1003  
 
PIQUR number: 
PQR309-009 
 
Document:   
Clinical Trial Protocol 
 
Date: 
April 24, 2020 
 
 
 
 
Page 1 of 81 




































































































































































































































































































































































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SAP_001.pdf: 
Study title: 
Single-arm Study With Bimiralisib in Patients With HNSCC Harboring NOTCH1 
Loss of Function Mutations 
 
ClinicalTrials.gov record number: 
NCT03740100 
 
MD Anderson protocol number: 
2018-1003  
 
PIQUR number: 
PQR309-009 
 
Document:   
Statistical Plan 
 
Date: 
September 24, 2018 
 
 
 
 
Page 1 of 2 
 
 
 
 


1.1 
Statistical hypotheses 
This is an open-label, single arm, two-stage study evaluating clinical efficacy, safety and 
pharmacokinetics of bimiralisib in patients with recurrent or metastatic HNSCC harboring 
NOTCH1 LOF mutations. The primary goal of the clinical trial is to determine the objective 
response rate (ORR, including confirmed complete and partial responses) in patients with r/m 
HNSCC harboring NOTCH1 to oral bimiralisib. An ORR of 10% or less is considered to be 
uninteresting and therefore this study has been designed with a reasonable power to detect a 
response rate of 30%.  
1.2 
Sample size determination 
To minimize accrual if bimiralisib is ineffective, a Simon’s optimal two-stage design is used.  In 
order to have 80% power to detect a response rate of 30%, (one-sided α=0.05 and β=0.20) up to 
10 patients will be enrolled in the first stage.  If 1 or 0 patient respond to the treatment, the trial 
will be closed due to futility and the treatment is considered ineffective. If two or more patients 
have an objective response, the study will enroll an additional 19 patients in the second stage.  The 
null hypothesis (H0: ORR ≤ 10%) will be rejected if the number of responses is ≥ 6 in 29 patients.  
If patients withdraw consent or drop out for other reasons unrelated to safety or disease 
progression, they may be replaced (see section Error! Reference source not found.). We 
anticipate up to 20% of patients to drop out, resulting in enrollment of up to 35 patients in total. 
This sample size is also reasonable to evaluate the pharmacokinetic and other correlative science 
endpoints; yet, no explicit sample size justification is made for these exploratory endpoints. 
 
Page 2 of 2