Single-arm Study With Bimiralisib in Patients With HNSCC Harboring NOTCH1 Loss of Function Mutations

NCT ID: NCT03740100

Last Updated: 2023-07-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-25
• Study Completion Date: 2020-12-09

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).

Conditions

HNSCC

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Open single arm

Bimiralisib capsules orally

Group Type: OTHER

Bimiralisib

Intervention Type: DRUG

Bimiralisib capsules

Interventions

Bimiralisib

Bimiralisib capsules

Intervention Type: DRUG

Other Intervention Names

PQR309, PI3K/mTOR inhibitor

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Faye M Johnson, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

MD Anderson Cancer Center Recruiting, Houston, Texas, US 77030

Locations

M.D. Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 36124629 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

http://www.mdanderson.org

M D Anderson Cancer Center

Other Identifiers

NCI-2019-02978

Identifier Type: OTHER

Identifier Source: secondary_id

2018-1003 (PQR309-009)

Identifier Type: -

Identifier Source: org_study_id