Phase Ib Study of BKM120 With Cisplatin and XRT in High Risk Locally Advanced Squamous Cell Cancer of Head and Neck

NCT02113878 | Completed Phase 1 Results DMC

• 1 other identifier: 14-008
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is evaluating a drug called buparlisib (BKM120) as a possible treatment for locally advanced head and neck squamous cell cancer.

Conditions

Carcinoma, Squamous Cell of Head and Neck; HPV Positive Oropharyngeal Squamous Cell Carcinoma; Hypopharyngeal Cancer; Early Invasive Cervical Squamous Cell Carcinoma; Carcinoma of Larynx; Cancer of Nasopharynx

Keywords

Carcinoma, Squamous Cell of Head and Neck; Human Papillomavirus Positive Oropharyngeal Carcinoma; Hypopharyngeal Cancer; Early Invasive Cervical Squamous Cell Carcinoma; Carcinoma of Larynx; Cancer of Nasopharynx

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose of Cisplatin

  The trial uses 3+3 design to determine maximum tolerated dose (MTD).

  While on treatment, up to 66 days

• Maximum Tolerated Dose of BKM120

  The trial uses 3+3 design to determine maximum tolerated dose (MTD).

  While on treatment, up to 66 days

Secondary Outcomes (6)

• Best Overall Response

  Measured at end of treatment, up to 66 days

• Median Time to Progression

  Up to 24 months (Progression is defined using RECIST v1.0 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions)

• 24 Month Overall Survival

  Up to 24 months

• Median Anxiety Score Change

  From baseline to cycle 9, up to 66 days.

• Median Depression Score Change

  From baseline to cycle 9, up to 66 days.

Study Arms (2)

Dose Level 1

EXPERIMENTAL

* 40 mg BKM120 will be administered orally daily for 45 days. Starting dose 40 mg. * Cisplatin: Starting Dose 30 mg/m2, given IV, weekly on days: (1, 8, 15, 22, 29, 36 and 43). * Radiotherapy: All participants will receive daily radiotherapy with intensity-modulated radiotherapy (IMRT) for 7 weeks.

Drug: BKM120; Drug: Cisplatin; Radiation: Intensity-modulated radiotherapy (IMRT)

Dose Level 2

EXPERIMENTAL

* 40 mg BKM120 will be administered orally daily for 45 days. * Cisplatin: Starting Dose 35 mg/m2, given IV, weekly on days: (1, 8, 15, 22, 29, 36 and 43). * Radiotherapy: All participants will receive daily radiotherapy with intensity-modulated radiotherapy (IMRT) for 7 weeks.

Drug: BKM120; Drug: Cisplatin; Radiation: Intensity-modulated radiotherapy (IMRT)

Interventions

BKM120 DRUG

BKM120 is a potent and highly specific oral pan-class I PI3K inhibitor.

Also known as: Buparlisib

Dose Level 1; Dose Level 2

Cisplatin DRUG

Cisplatin is a chemotherapy drug

Also known as: Platinol-AQ, Platinol

Dose Level 1; Dose Level 2

Intensity-modulated radiotherapy (IMRT) RADIATION

IMRT is the medical use of ionizing radiation, generally as part of cancer treatment to control or kill malignant cells

Also known as: IMRT

Dose Level 1; Dose Level 2

Eligibility Criteria

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

You may qualify if:

• Stage III/IV, locally advanced, biopsy proven squamous cell cancer of the head and neck that undergo chemoradiation as their primary treatment with curative intent.
• Oropharynx (HPV positive and HPV negative), hypopharynx, larynx primaries, nasopharynx as well as those with documented SCC of the cervical lymph nodes, with unknown primaries.
• \>10 pack years of tobacco use
• Age ≥ 18 years
• ECOG performance status ≤ 2
• At least one site of measurable disease
• Adequate bone marrow function as shown by: ANC \> 1.5 x 109/L, Platelets \>100 x 109/L, Hb \>9 g/dL
• Total calcium (corrected for serum albumin) within normal limits
• Magnesium ≥ the lower limit of normal
• Potassium within normal limits for the institution.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range
• Serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome)
• Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min
• Serum amylase ≤ ULN
• Serum lipase ≤ ULN

You may not qualify if:

• Distant metastatic disease
• Less than or equal to 10 pack years of tobacco history
• Received prior chemotherapy
• Received prior radiation to the head and neck or adjacent anatomical site
• Received prior treatment with a P13K inhibitor.
• Known hypersensitivity to BKM120 or to its excipients
• Acute or chronic liver, renal disease or pancreatitis
• Mood disorders ≥ CTCAE grade 3
• Diarrhea ≥ CTCAE grade 2
• Active cardiac disease
• History of cardiac dysfunction including any of the following:
• Patient has poorly
• Impairment of gastrointestinal (GI) function
• Currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug.
• Chronic treatment with steroids or another immunosuppressive agent.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Glorieux M, Dok R, Nuyts S. The influence of PI3K inhibition on the radiotherapy response of head and neck cancer cells. Sci Rep. 2020 Oct 1;10(1):16208. doi: 10.1038/s41598-020-73249-z.

  PMID: 33004905 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Nasopharyngeal Neoplasms

Interventions

NVP-BKM120; Cisplatin; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Nasopharyngeal Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Results Point of Contact

• Title: Glenn J. Hanna, MD
• Organization: Dana Farber Cancer Institute

GJHanna@partners.org

617.632.6799

Study Officials

• Glenn J. Hanna, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 1, 2014
• First Posted: April 15, 2014
• Study Start: September 29, 2014
• Primary Completion: December 6, 2019
• Study Completion: January 1, 2022
• Last Updated: November 5, 2024
• Results First Posted: November 5, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)