Recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) harboring a PI3KCA mutation/amplification and/or a PTEN loss MedDRA version: 19.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Copanlisib
Product Code: BAY 80-6946
Pharmaceutical Form: Solution for injection
Trade Name: ERBITUX
Pharmaceutical Form:
Sponsors
UNICANCER
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with R/M HNSCC (oropharynx, oral cavity, hypopharynx and larynx), histologically or cytologically confirmed, not amenable to curative treatment with surgery and/or chemotherapy and/or radiotherapy (Stage III/IV) 2. Adult men and women = 18 years 3. Patients with ECOG performance status 0 – 2 (ECOG: Eastern Cooperative Oncology Group) 4. Patients with tumor harboring a PI3K mutation/amplification and/or a PTEN loss 5. Patients with a radiologic documented progression or relapse after cetuximab therapy (patients could have either received combination platinum doublet with cetuximab or cetuximab after platinum doublet) 6. Patients with prior platinum based therapy, unless contraindicated 7. Patients with at least one measurable lesion assessed by Magnetic Resonance Imaging (MRI) or a computerized tomography scanner (CT-scan) according to RECIST 1.1. Patients must have clinically and/or radiographically documented measurable disease. At least one site of disease must be unidimensionally measurable as follows • CT-scan, physical exam = 10 mm • Lymph node short axis = 15 mm Tumor measurements must be performed within 28 days prior to registration. 8. Women of childbearing potential and men must agree to use adequate contraception when sexually active. This applies since signing of the informed consent form and up to12 months (for women of child bearing potential) and 6 months (for fertile men) after the last study drug administration. Highly effective contraception methods are detailed in section 7.1. 9. Women of childbearing age or sexually active female patients with reproductive potential must have a negative pregnancy test (serum or urine within the 7 days prior to starting study drug). 10. Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses 11. Patients with social insurance coverage Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 32 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 32
Exclusion criteria
Exclusion criteria: 1. Patients previously treated with PI3K and/or mTOR inhibitors 2. Patients with anticancer therapy within 14 days (i.e. palliative radiotherapy) or investigational treatment within 28 days prior to the initiation of study drug treatment 3. Patients currently using other approved or investigational anti-neoplasic agent 4. Patients with uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management), Congestive heart failure > New York Heart Association (NYHA) class 2, Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before start of test drug No active cardiac disease including any of the following: left ventricular ejection fraction (LVEF) 470 ms on screening ECG 5. Patients with uncontrolled diabetes mellitus (patients with controlled diabetes mellitus will be eligible but only into the phase II of the study and only if fasting HbA1c = 8.5% or fasting glucose = 160 mg/dl glucose) 6. Patients with another active malignancy. Subjects who have had another malignancy and have been disease-free for 3 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible 7. Patients with a history of Human Immunodeficiency Virus (HIV) Hepatitis B (HBV) or hepatitis C (HCV) infection. All patients must be screened for HIV, HBV and HCV up to 28 days prior to first dosing using the routine virus laboratorial panel. Patients who are positive for HBs Ag or HBc Ab will be eligible if they are negative for HBV-DNA. Patients who are positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA 8. Patients with active uncontrolled or symptomatic central nervous system (CNS) metastases. Patients are eligible if their disease is controlled at least 30 days on corticosteroids prior to starting study drug. 9. Patients with major surgery within 28 day prior to starting study drug. Patients must have recovered from major side effects of the surgery. 10. Patients with radiotherapy within 14 days prior to starting study drug. Patients must have recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia). 11. Patients receiving any medications or substances that are inhibitors or inducers of CYP3A4 are ineligible 12. Patients with altered hematopoietic or organ function, as indicated by the following criteria (assessed within -7 days prior the first dosing): • Absolute granulocytes 2.5 x ULN in the absence of or > 5x ULN in the presence of liver metastases • Bilirubin > 1.5 x ULN (except Gilbert Syndrome : 1.0 x ULN • Lipase > 1.5 x ULN • INR and PTT > 1.5 x ULN 13. Patients with a history of hypersensitivity to other monoclonal antibodies or to the active or inactive exci
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary endpoints are: • Regarding the Phase Ib, the occurrence of DLT • Regarding the Phase II, the PFS (Progression Free Survival) at Week 16 ; Timepoint(s) of evaluation of this end point: • Regarding the Phase Ib, anytime • Regarding the Phase II, at Week 16 ;Main Objective: The primary objective of this study is to determine the MTD of copanlisib used in combination with cetuximab and the RP2D in the phase Ib part and to evaluate the efficacy of the combination at the RP2D in the phase II. Determination of the MTD will be based on the occurrence of DLT during cycle 1.;Secondary Objective: The primary objective of this study is to determine the MTD of copanlisib used in combination with cetuximab and the RP2D in the phase Ib part and to evaluate the efficacy of the combination at the RP2D in the phase II. Determination of the MTD will be based on the occurrence of DLT during cycle 1. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: -; Secondary end point(s): The main secondary endpoints of the study are : • The efficacy data assessed by measuring the OS and ORR. These endpoints are defined as follows: OS is defined as the time from first dosing date to the date of death. A patient who has not died will be censored at last known date alive. OS will be followed continuously while patients are on the treatment and up to 12 months via in-person or phone contact after patients discontinue the study drug. Objective response rate (ORR) is defined as the number and percentage of patients with a Best Overall Response (BOR) of confirmed complete response (CR) or partial response (PR). Best overall response (BOR) is defined as the best response designation, recorded between the date of first dose and the date of the initial objectively documented tumor progression per RECIST v1.1 or the date of subsequent therapy, whichever occurs first. For Patients without documented progression or subsequent therapy, all available response designations will contribute to the BOR determination. • Safety and tolerability will be measured by the incidence of all adverse events, serious adverse events, deaths and laboratory abnormalities. Adverse event assessments and laboratory tests will be performed at baseline, and continuously throughout the study at the beginning of each subsequent cycle using the CTCAE version 4.03. | — |
Countries
France
Contacts
Public ContactJessy DELAYE
UNICANCER
Outcome results
None listed