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

NCT03740100 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2018-1003 (PQR309-009)NCI-2019-02978
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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

Keywords

Head and Neck Squamous Cell Carcinoma; Notch 1 loss of function mutation; PI3K/mTOR Inhibitor; Refractory metastatic

Outcome Measures

Primary Outcomes (1)

• 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

  At 6 and 12 weeks after the start of therapy (± 3 days)

Study Arms (1)

Open single arm

OTHER

Bimiralisib capsules orally

Drug: Bimiralisib

Interventions

Bimiralisib DRUG

Bimiralisib capsules

Also known as: PQR309, PI3K/mTOR inhibitor

Open single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 36124629 DERIVED

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The trial was closed early because the sponsor became insolvent.

Results Point of Contact

• Title: Dr. Faye Johnson
• Organization: MD Anderson Cancer Center

fmjohns@mdanderson.org

7137922121

Study Officials

• Faye M Johnson, MD,PhD

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Oral administration

Study Record Dates

• First Submitted: November 1, 2018
• First Posted: November 14, 2018
• Study Start: January 25, 2019
• Primary Completion: August 5, 2020
• Study Completion: December 9, 2020
• Last Updated: July 14, 2023
• Results First Posted: January 20, 2022

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)