Phase Ib/II trial of copanlisib, a selective PI3K inhibitor, in combination with cetuximab in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) harboring a PI3KCA mutation/amplification and/or a PTEN loss

Phase 1

• Conditions: 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); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-004340-19-FR
• Lead Sponsor: ICANCER

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-04-26
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 32

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

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) < 50% as determined by Multiple Gated Acquisition (MUGA) scan or echocardiogram (ECHO) and QTc > 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 < 1.0 ×109/L
•Platelets < 75 x 109/L
•ALAT/ASAT > 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 : < 3.0 mg/dL)
•Creatinine clearance < 60 mL/min (measured or calculated by Cockcroft and Gault formula) or serum creatinine > 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified