Activity and Safety Study of BKM120 in Monotherapy in Patient With Metastatic Head and Neck Cancer Recurrent or Progressive

NCT01737450 | Completed Phase 2 DMC

• 2 other identifiers: ET12-0342012-002403-18
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 9

Brief Summary

The aim of this study is to determine the activity, to assess the safety and tolerance of BKM120 in adult patients with recurrent or metastatic head and neck cancer progressive under platin and cetuximab-based chemotherapy.

Conditions

Head and Neck Neoplasms; Neoplasm Metastasis; Recurrent Disease; Progressive Disease

Keywords

Metastatic head and neck cancer; PI3K inhibitor; Recurrent head and meck cancer; Progressive head and neck cancer; BKM120

Outcome Measures

Primary Outcomes (1)

• 2 months disease control rate

  Control rate= Complete response, partial response and stable disease according to RECIST 1.1

  2 months after the first BKM120 intake

Secondary Outcomes (6)

• Progression free survival

  At 2 months, 4 months and then every 2 months

• Overall survival (OS)

  Baseline, at 2 months, 4 months and then every 2 months at the end of Study

• Safety

  continuous up to 30 days after the last treatment

• Objective response rate

  At Baseline, 2 months, 4 months and then every 2 months, at the end of Study

• Duration of response

  At Baseline, 2 months, 4months and then every 2 months, at the end of Study

Study Arms (1)

BKM120

EXPERIMENTAL

Full dose=100 mg/day (oral route) One study cycle equals 28 days. Patients will be treated until disease progression, unacceptable toxicity, or willingness to stop.

Drug: BKM120

Interventions

BKM120 DRUG

Also known as: Buparlisib

BKM120

Eligibility Criteria

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

You may qualify if:

• \. Adult men and women ≥ 18 years at the day of inform consent signature.
• \. Patients with metastatic or relapsed squamous cell head and neck carcinoma .
• \. Documented progression or relapse after platin and cetuximab or anti-epidermal growth factor receptor (EGFR) -based chemotherapy at time of study drug start
• \. Documented mutational status of PIK3CA before study drug start
• \. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 .
• \. At least one measurable lesion by CT-scan as per RECIST 1.1 .
• \. Life expectancy \> 12 weeks.
• \. Patients must be able to swallow capsules.
• \. Adequate bone marrow, renal and liver function as defined by the following tests :
• Absolute neutrophil count ≥ 1.0 x 109/L,
• Platelet count \> 100 x 109/L,
• Haemoglobin value above 9 g/dL,
• international normalized ratio (INR) ≤ 1.5
• Serum Creatinine ≤ 1.5 upper limit of normal (ULN)
• Glomerular filtration rate calculated using Cockcroft-Gault formula \> 60ml/min (or MDRD formula for patients older than 65 years)

You may not qualify if:

• \. Patient having received previous treatment with PI3K and/or mammilian target of rapamycin (mTOR) inhibitors.
• \. Patient with symptomatic central nervous system (CNS) metastases.
• \. Patient with a concurrent malignancy or has a malignancy within 3 years of study enrollment, (with the exception of adequately treated basal or squamous cell carcinoma or non-melanomatous skin cancer).
• \. Patient has any of the following mood disorders as judged by the Investigator or a Psychiatrist:
• Medically documented history of or 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),
• Patients with active severe personality disorders (defined according to Diagnostic and Statistical Manual (DSM) - IV) are not eligible.
• Note: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug.
• ≥ CTCAE grade 3 anxiety,
• or meets the cut-off score of ≥ 12 in the Patient Health Questionnaire (PHQ) -9 or a cut-off of ≥ 15 in the generalized anxiety disorder (GAD) -7 mood scale, respectively,
• or selects a positive response of '1, 2, or 3' to question number 9 regarding potential for suicidal thoughts ideation in the PHQ-9 (independent of the total score of the PHQ-9).
• \. Patient concurrently using other approved or investigational anti-neoplasic agent.
• \. Patient who has received anticancer therapy \< 2 weeks or investigational treatment \< 4 weeks prior the initiation of study drug.
• \. Patient who has received radiotherapy ≤ 4 weeks prior to starting study drug or who have not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia).
• \. Patient having had major surgery within 14 days prior to starting study drug or has not recovered from major side effects of the surgery.
• \. Patient with poorly controlled diabetes mellitus (i.e. HbA1c \> 8 %)

Sponsors & Collaborators

• Centre Leon Berard: lead
• National Cancer Institute, France: collaborator
• Fondation ARC: collaborator

Study Sites (9)

Hopital St André

Bordeaux, France

Location

Hôpital BEAUJON

Clichy, France

Location

Centre Oscar Lambret

Lille, France

Location

Centre Léon Bérard

Lyon, France

Location

Centre Val d'Aurelle - Paul Lamarque

Montpellier, France

Location

Centre Antoine LACASSAGNE

Nice, France

Location

Institut Curie

Paris, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69003, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Related Publications (5)

• Graupera M, Guillermet-Guibert J, Foukas LC, Phng LK, Cain RJ, Salpekar A, Pearce W, Meek S, Millan J, Cutillas PR, Smith AJ, Ridley AJ, Ruhrberg C, Gerhardt H, Vanhaesebroeck B. Angiogenesis selectively requires the p110alpha isoform of PI3K to control endothelial cell migration. Nature. 2008 May 29;453(7195):662-6. doi: 10.1038/nature06892. Epub 2008 Apr 30.

  PMID: 18449193 BACKGROUND

• Schnell CR, Stauffer F, Allegrini PR, O'Reilly T, McSheehy PM, Dartois C, Stumm M, Cozens R, Littlewood-Evans A, Garcia-Echeverria C, Maira SM. Effects of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 on the tumor vasculature: implications for clinical imaging. Cancer Res. 2008 Aug 15;68(16):6598-607. doi: 10.1158/0008-5472.CAN-08-1044.

  PMID: 18701483 BACKGROUND

• Vokes EE, Weichselbaum RR, Lippman SM, Hong WK. Head and neck cancer. N Engl J Med. 1993 Jan 21;328(3):184-94. doi: 10.1056/NEJM199301213280306. No abstract available.

  PMID: 8417385 BACKGROUND

• Saranath D, Panchal RG, Nair R, Mehta AR, Sanghavi VD, Deo MG. Amplification and overexpression of epidermal growth factor receptor gene in human oropharyngeal cancer. Eur J Cancer B Oral Oncol. 1992 Oct;28B(2):139-43. doi: 10.1016/0964-1955(92)90043-z.

  PMID: 1306731 BACKGROUND

• Burtness B. The role of cetuximab in the treatment of squamous cell cancer of the head and neck. Expert Opin Biol Ther. 2005 Aug;5(8):1085-93. doi: 10.1517/14712598.5.8.1085.

  PMID: 16050785 BACKGROUND

MeSH Terms

Conditions

Head and Neck Neoplasms; Neoplasm Metastasis; Recurrence; Disease Progression

Interventions

NVP-BKM120

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Study Officials

• Jérome FAYETTE, MD

  Centre Léon Bérard, Lyon- FRANCE

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 13, 2012
• First Posted: November 29, 2012
• Study Start: January 1, 2013
• Primary Completion: September 1, 2018
• Study Completion: March 1, 2019
• Last Updated: June 24, 2019

Record last verified: 2019-06

Locations

FR (9)