ABORL - A Phase II trial aiming to evaluate the clinical interest of ABEMACICLIB in patients with locally advanced/metastatic head and neck cancer harboring an homozygous deletion of CDKN2A, and/or an amplification of CCND1 and/or of CDK6 refractory to standards treatments
- Conditions
- Patients with locally advanced/metastatic head and neck cancer after failure of platinum and cetuximab or anti-EGFR-basedMedDRA version: 20.0Level: PTClassification code 10067821Term: Head and neck cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-004537-25-FR
- Lead Sponsor
- Centre Léon Bérard
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 25
INCLUSION CRITERIA
I1.Male or female patients aged = 18 years at time of inform consent signature.
I2.Histologically proven metastatic or locally advanced HNSCC (oropharynx, oral cavity, hypopharynx and larynx). Patients with cancer of nasopharynx (i.e. cavum cancer) are not eligible.
I3.Availability of a representative formalin-fixed paraffin-embedded (FFPE) primary and/or metastatic tumor tissue with an associated pathology report for molecular screening:
-Either an archival block
-Either a dedicated freshly collected tumor biopsy.
I4.Documented CDKN2A homozygous deletion and/or CCND1 amplification and/or CDK6 amplification before C1D1.
Note: This molecular pre-screening will be centralized at the CGH platform of CLB using pre-treatment FFPE tumor sample.
Note: This molecular pre-screening can be performed for non-progressive patient but study drug treatment cannot be initiated until confirmed PD according to RECIST criteria..
I5.HPV negative tumor status must be documented before C1D1.
Note: This analysis will be centralized and performed by translational Biopathology platform of CLB during molecular screening by IHC with p16.
I6.Documented radiological progression or relapse after platin and cetuximab or anti-EGFR-based chemotherapy (combination or sequential treatment) at time of C1D1.
I7.At least one measurable lesion by CT-scan as per RECIST 1.1.
I8.At least one biopsiable tumor lesion at time of inclusion i.e. at least one lesion with a diameter of at least 10 mm, visible by medical imaging and accessible to percutaneous sampling.
I9.Eastern Cooperative Oncology Group (ECOG) performance status: 0 or 1.
I10.Life expectancy > 12 weeks.
I11.Patients must be able to swallow capsules.
I12.Adequate organ and bone marrow function as defined in the protocol
I13.Women of childbearing potential (entering the study after a confirmed menstrual period and who have a negative pregnancy test within 7 days before C1D1) must agree to use two methods of medically acceptable forms of contraception from the date of negative pregnancy test to 3 months after the last study drug intake.
I14.Fertile males must use a highly effective contraception during dosing period and through 3 months after final dose of study drug.
I15.Patient should be able and willing to comply with study visits and procedures as per protocol.
I16.Patient should understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures performed.
I17.Patients must be covered by a medical insurance.
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 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7
NI1.Cancer disease considered curable with surgery or radiotherapy.
NI2.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).
NI3.Patient with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of abemaciclib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
NI4.Patient has other concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment contraindicate her participation in the clinical study (for example, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn’s disease or ulcerative colitis).
NI5.Persisting significant toxicities related to prior treatments i.e. = Grade 2 AE according to CTCAE V4.03 except alopecia (any grade) and biological values as defined in inclusion criteria.
NI6.Hypersensitivity to the active substance or excipient of study drug
NI7Have received prior treatment with any CDK4/6 inhibitor (or participated in any CDK4/6 inhibitor clinical trial for which treatment assignment is still blinded).
NI8.Patient has received treatment with a drug that has not received regulatory approval for any indication within:
-14 days of C1D1 for non myelosuppressive agent or
-21 days of C1D1 for a myelosuppressive agent.
NI9.Patient has had major surgery within 14 days prior to C1D1.
NI10.Patient has received within 28 days prior to C1D1 yellow fever vaccine
NI11.Patient has a personal history within the last 12 months prior to C1D1 of any of the following conditions: syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest.
NI12.Patient needs for the following concomitant medications/interventions not permitted during the study treatment period :
-Any investigational anticancer therapy other than the study drug.
-Any concurrent chemotherapy, radiotherapy (except palliative radiotherapy after discussion with the Sponsor), immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable.
-Major surgery.
-Strong and moderate inhibitors and inducers of CYP3A (for example Grapefruit juice, phenytoin and carbamazepine).
-Enzyme-Inducing Anti-Epileptic Drugs (EIAED).
NI13.Patient has received an autologous or allogeneic stem-cell transplant.
NI14.Patient has an active systemic fungal and/or known viral infection (for example, human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C antibodies).
NI15.Pregnant or breast-feeding female patients.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the clinical activity of ABEMACICLIB as measured by the 8-week non-progression rate (Complete response [CR] + Partial Response [PR] + Stable disease [SD] after 8 weeks of treatment according to RECIST v1.1) in adult patients with locally advanced or metastatic head and neck cancer progressive under platin and cetuximab or anti-EGFR-based chemotherapy.;Secondary Objective: To further assess the clinical activity of ABEMACICLIB as measured by Objective response rate (ORR), duration of response, time to progression (TTP) and time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS).<br><br>To assess the safety of ABEMACICLIB in this patient population.<br><br>;Primary end point(s): the non-progression rate (Complete response [CR] + Partial Response [PR] + Stable disease [SD] after 8 weeks of treatment according to RECIST v1.1) <br><br>;Timepoint(s) of evaluation of this end point: 8 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Objective response rate (ORR), duration of response, time to progression (TTP) and time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS).<br><br>Incidence of AE and SAEs;Timepoint(s) of evaluation of this end point: 12 months