Study of BKM120 in Advanced Squamous Cell Carcinoma of Head and Neck
Primary Purpose
Head Neck Cancer Squamous Cell Metastatic, Head Neck Cancer Squamous Cell Recurrent
Status
Unknown status
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
BKM120
Sponsored by
About this trial
This is an interventional treatment trial for Head Neck Cancer Squamous Cell Metastatic focused on measuring BKM120, head and neck cancer, squamous cell carcinoma
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed recurrent or metastatic squamous-cell carcinoma of head and neck (SCCHN), except nasopharyngeal carcinoma
- Disease not amenable to curative treatment (surgery or radiation for curative intent)
- 20 years of age or older
Progressive disease defined as follows
- after one or two prior chemotherapy regimens including platinum-based chemotherapy given for palliation
- within 6 months after concurrent chemoradiotherapy (including induction chemotherapy) delivered as part of primary treatment.
- Life expectancy of at least 12 weeks
- At least one measurable lesion according to the RECIST 1.1 criteria.
- ECOG performance score of 0 ~ 2
Adequate organ function
- Absolutely Neutrophil Count (ANC) ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hemoglobin ≥ 9.0 g/dL
- Serum Creatinine ≤ 1.5 x ULN
- Adequate liver function (total bilirubin ≤ 2.0 x ULN, AST and ALT ≤ 2.0 x ULN or < 5.0 x ULN if liver metastases are present)
- Availability of tissue samples (archival tissue or rebiopsied tissues) for molecular analysis (representative paraffin block or unstained sections from tumor diagnostic specimen are mandatory)
- Patients who have will and ability to comply with the scheduled visits, the treatment plan, laboratory tests and any other trial procedures
- Patient's informed consent
Exclusion Criteria:
- Nasopharyngeal carcinoma
- More than two prior lines of chemotherapy in the palliative setting.
- Uncontrolled, untreated brain metastasis Patients with controlled and asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases ≥ 28 days (must include radiotherapy and/or surgery) and, if on corticosteroid therapy, should be receiving a stable low dose (e.g. dexamethasone 4 mg or equivalent dose of another corticosteroid for at least 14 days before start of study treatment)
- Surgery, chemotherapy or irradiation within 4 weeks of study entry
- Prior treatment with any investigational drug within the preceding 4 weeks
- Concomitant chemotherapy, hormonal therapy or immunotherapy
- Previous or concomitant malignant disease, except adequately treated basal cell cancer of the skin or cervical cancer in situ, superficial bladder tumors (Ta, Tis & T1) or any cancer curatively treated > 5 years prior study entry
- Patient who cannot take the oral drug
- Patient is pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL).
- Clinically significant psychological disorders including mood and anxiety disorders judged by psychiatry physician
- Patient who have not recovered to grade 1 or better from any adverse events (except alopecia) related to previous antineoplastic therapy before screening procedures are initiated
Severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial.
- Patient has poorly controlled diabetes mellitus (HbA1c> 8 %)
- Patient has history of cardiac dysfunction including history of documented congestive heart failure (New York Heart Association functional classification III-IV) and documented cardiomyopathy
- Patient is currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes. * Active infection, inflammatory bowel disease
- Inadequate liver function (total bilirubin ≥ 2.0 x ULN, AST and ALT ≥ 2.0 x ULN or ≥ 5.0 x ULN if liver metastases are present)
Sites / Locations
- Severance HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
BKM120
Arm Description
Outcomes
Primary Outcome Measures
Disease control rate at 8 weeks
The disease control rate (DCR) is defined as the proportion of randomized patients achieving a best overall response of PR or CR or SD, defined by RECIST criteria (version 1.1), relative to the total number of patients in the considered analysis population (ITT).
Secondary Outcome Measures
Overall response rate (ORR)
Overall objective response rate (ORR) is the best response rate stipulated as complete response (CR) or partial response (PR) (target lesion and tumor response defined according to RECIST guideline version 1.1) and identified as percentage of the confirmed patients.
Toxicity profile
From C1D1 to 1 months after the last dose adminitration
Overall safety profile verified as relevance of adverse events and laboratory abnormality in the study and grades granted based on (USA National Cancer Center) Common Terminology Criteria for Adverse Events such as the type, frequency and severity (CTCAE), v4.0.
Overall survival
From C1D1 to death
Progression-free survival
From C1D1 until confirmed disease progression or death
Quality of life assessment
Quality of life assessment will be performed using FACT-HN& questionnaire
FACT-H&N questionnaire includes physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and head & neck cancer subscale (HNCS).
Patients will be evaluation on baseline, day 1 of every cycle (4 weeks), and end of treatment.
Time to progression (TTP)
From C1D1 until confirmed disease progression.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01527877
Brief Title
Study of BKM120 in Advanced Squamous Cell Carcinoma of Head and Neck
Official Title
An Open Label, Single Arm, Multicenter Phase II Study of BKM120 in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck Who Failed to Respond to Platinum-based Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
October 2012
Overall Recruitment Status
Unknown status
Study Start Date
September 2012 (undefined)
Primary Completion Date
December 2013 (Anticipated)
Study Completion Date
August 2014 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Yonsei University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is to evaluate disease control rate (DCR) at 8 weeks of BKM120 administered as therapy for patient with recurrent/metastatic head and neck squamous cell carcinoma.
Detailed Description
One promising approach to the treatment of cancer is inhibition or modulating the crucial signal transduction pathway of PI3K-Akt-mTOR. Several PI3K inhibitors are being tested in the clinical trials for cancer treatment but not for the head and neck cancer yet. BKM120 is a specific Pan-class I PI3K inhibitor. We suggest multicenter single arm phase II study to determine anti-tumor effects of BKM120 in patients with recurrent and/or metastatic SCCHN who failed to prior platinum-based chemotherapy regimens.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head Neck Cancer Squamous Cell Metastatic, Head Neck Cancer Squamous Cell Recurrent
Keywords
BKM120, head and neck cancer, squamous cell carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
53 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
BKM120
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
BKM120
Other Intervention Name(s)
NVP-BKM120, BKM-120
Intervention Description
Patients will be instructed to take BKM120 orally at a dose of 100 mg with a glass of water once daily, in a fasting state or with a light fat-free meal, and as close as possible to the same time each day. The patient will be dosed on a flat scale of mg/day and not be adjusted to body weight or body surface area. If vomiting occurs no attempt should be made to replace the dose.
• BKM120 should be taken 1-hour following a light meal. Please note that patients must avoid consumption of Seville orange (and juice), grapefruit or grapefruit juice, grapefruit hybrids, pummelos and exotic citrus fruits from 7 days prior to the first dose of study drug and during the entire study treatment period due to potential CYP3A4 interaction. Regular orange juice is allowed.
Primary Outcome Measure Information:
Title
Disease control rate at 8 weeks
Description
The disease control rate (DCR) is defined as the proportion of randomized patients achieving a best overall response of PR or CR or SD, defined by RECIST criteria (version 1.1), relative to the total number of patients in the considered analysis population (ITT).
Time Frame
Eight weeks after administration of the drug
Secondary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
Overall objective response rate (ORR) is the best response rate stipulated as complete response (CR) or partial response (PR) (target lesion and tumor response defined according to RECIST guideline version 1.1) and identified as percentage of the confirmed patients.
Time Frame
Every 8 weeks from date of first treatment until date of last treatment up to 24 months
Title
Toxicity profile
Description
From C1D1 to 1 months after the last dose adminitration
Overall safety profile verified as relevance of adverse events and laboratory abnormality in the study and grades granted based on (USA National Cancer Center) Common Terminology Criteria for Adverse Events such as the type, frequency and severity (CTCAE), v4.0.
Time Frame
Every 4 weeks from date of first treatment until date of last treatment up to 24 months
Title
Overall survival
Description
From C1D1 to death
Time Frame
Every 8 weeks from date of first treatment until the date of death from any cause, assessed approximately up to 24 months
Title
Progression-free survival
Description
From C1D1 until confirmed disease progression or death
Time Frame
Every 8 weeks from date of first treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed approximately up to 24 months
Title
Quality of life assessment
Description
Quality of life assessment will be performed using FACT-HN& questionnaire
FACT-H&N questionnaire includes physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and head & neck cancer subscale (HNCS).
Patients will be evaluation on baseline, day 1 of every cycle (4 weeks), and end of treatment.
Time Frame
Every 4 weeks from date of first treatment until the date of death from any cause, assessed approximately up to 24 months
Title
Time to progression (TTP)
Description
From C1D1 until confirmed disease progression.
Time Frame
Every 8 weeks from date of first treatment until the date of first documented progression, assessed approximately up to 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed recurrent or metastatic squamous-cell carcinoma of head and neck (SCCHN), except nasopharyngeal carcinoma
Disease not amenable to curative treatment (surgery or radiation for curative intent)
20 years of age or older
Progressive disease defined as follows
after one or two prior chemotherapy regimens including platinum-based chemotherapy given for palliation
within 6 months after concurrent chemoradiotherapy (including induction chemotherapy) delivered as part of primary treatment.
Life expectancy of at least 12 weeks
At least one measurable lesion according to the RECIST 1.1 criteria.
ECOG performance score of 0 ~ 2
Adequate organ function
Absolutely Neutrophil Count (ANC) ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hemoglobin ≥ 9.0 g/dL
Serum Creatinine ≤ 1.5 x ULN
Adequate liver function (total bilirubin ≤ 2.0 x ULN, AST and ALT ≤ 2.0 x ULN or < 5.0 x ULN if liver metastases are present)
Availability of tissue samples (archival tissue or rebiopsied tissues) for molecular analysis (representative paraffin block or unstained sections from tumor diagnostic specimen are mandatory)
Patients who have will and ability to comply with the scheduled visits, the treatment plan, laboratory tests and any other trial procedures
Patient's informed consent
Exclusion Criteria:
Nasopharyngeal carcinoma
More than two prior lines of chemotherapy in the palliative setting.
Uncontrolled, untreated brain metastasis Patients with controlled and asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases ≥ 28 days (must include radiotherapy and/or surgery) and, if on corticosteroid therapy, should be receiving a stable low dose (e.g. dexamethasone 4 mg or equivalent dose of another corticosteroid for at least 14 days before start of study treatment)
Surgery, chemotherapy or irradiation within 4 weeks of study entry
Prior treatment with any investigational drug within the preceding 4 weeks
Concomitant chemotherapy, hormonal therapy or immunotherapy
Previous or concomitant malignant disease, except adequately treated basal cell cancer of the skin or cervical cancer in situ, superficial bladder tumors (Ta, Tis & T1) or any cancer curatively treated > 5 years prior study entry
Patient who cannot take the oral drug
Patient is pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL).
Clinically significant psychological disorders including mood and anxiety disorders judged by psychiatry physician
Patient who have not recovered to grade 1 or better from any adverse events (except alopecia) related to previous antineoplastic therapy before screening procedures are initiated
Severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial.
Patient has poorly controlled diabetes mellitus (HbA1c> 8 %)
Patient has history of cardiac dysfunction including history of documented congestive heart failure (New York Heart Association functional classification III-IV) and documented cardiomyopathy
Patient is currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes. * Active infection, inflammatory bowel disease
Inadequate liver function (total bilirubin ≥ 2.0 x ULN, AST and ALT ≥ 2.0 x ULN or ≥ 5.0 x ULN if liver metastases are present)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Byoung Chul Cho, M.D., Ph.D.
Phone
82-2-2228-8126
Email
cbc1971@yuhs.ac
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Byoung Chul Cho, M.D., Ph.D.
Organizational Affiliation
Yonsei University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Severance Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Byoung Chul Cho, MD
Phone
82-2-2228-8126
Email
cbc1971@yuhs.ac
First Name & Middle Initial & Last Name & Degree
Byoung Chul Cho, M.D., Ph.D.
12. IPD Sharing Statement
Citations:
PubMed Identifier
32963347
Citation
Kim HR, Kang HN, Yun MR, Ju KY, Choi JW, Jung DM, Pyo KH, Hong MH, Ahn MJ, Sun JM, Kim HS, Kim J, Yoo J, Kim KR, Koh YW, Kim SH, Choi EC, Yoon SO, Shim HS, Paik S, Kim TM, Cho BC. Mouse-human co-clinical trials demonstrate superior anti-tumour effects of buparlisib (BKM120) and cetuximab combination in squamous cell carcinoma of head and neck. Br J Cancer. 2020 Dec;123(12):1720-1729. doi: 10.1038/s41416-020-01074-2. Epub 2020 Sep 23.
Results Reference
derived
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Study of BKM120 in Advanced Squamous Cell Carcinoma of Head and Neck
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