A Phase II Trial Aiming to Evaluate the Clinical Interest of ABEMACICLIB Monotherapy in Patients With Locally Advanced/Metastatic Head and Neck Cancer After Failure of Platinum and Cetuximab or Anti-EGFR-based Therapy and Harboring an Homozygous Deletion of CDKN2A, and/or an Amplification of CCND1 and/or of CDK6
Overview
- Phase
- Phase 2
- Intervention
- Abemaciclib
- Conditions
- Head and Neck Cancer
- Sponsor
- Centre Leon Berard
- Enrollment
- 25
- Locations
- 3
- Primary Endpoint
- The 8-week non-progression rate defined as the rate of patients with complete response (CR), partial response (PR) or stable disease (SD) lasting at least 8 weeks, according to RECIST v1.1
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This trial is an open-label, single arm, Phase II study using an A'Hern single stage design.
The molecular prescreening step will allow to defined HPV tumor status as well as molecular status CDKN2A, CCND1 and CDK6. Following this centralized molecular screening, only patients with HPV negative status and with tumor harboring CDKN2A homozygous deletion and/or CCND1 amplification and/or CDK6 amplification could initiate abemaciclib at time of documented radiological progression. Patients will be treated with ABEMACICLIB, 400 mg/day with 2 doses of 200 mg 12 hour apart (QH12). A cycle is defined as an interval of 28 days. For each 28-day cycle, a total of 56 doses of study drug will be dispensed.
Detailed Description
SAMPLE SIZE DETERMINATION The primary endpoint is the non-progression rate (CR, PR, SD as per RECIST 1.1) after 8 weeks of treatment. The sample size calculation was based on an A'Hern single stage phase II design, with a minimum success (non- progression) rate considered of interest of p1=40% and an uninteresting rate of p0=15%. Assuming a type I error alpha of 0.05 and 85% power, 23 patients are needed to reject the null hypothesis H0: p\<=p0 vs the alternative hypothesis H1: p ≥ p1 in a unilateral situation. Based on the assumption that 10% of the patients may be non-evaluable, 25 patients will be included in the study. DATA ENTRY AND DATA MANAGEMENT All the data concerning the patients will be recorded in the eCRF throughout the study. SAE reporting will be paper-based by Fax. The sponsor will perform the study monitoring and will help the investigators to conduct the study in compliance with the clinical trial protocol, Good Clinical Practices (GCP) and local low requirements.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female patients aged ≥ 18 years at time of inform consent signature
- •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
- •Availability of a representative formalin-fixed paraffin-embedded (FFPE) primary and/or metastatic tumor tissue with an associated pathology report for molecular pre-screening: either an archival tumor block or a dedicated freshly collected tumor biopsy.
- •Documented CDKN2A homozygous deletion and/or CCND1 amplification and/or CDK6 and/or CDK4 amplification and no deletion/losses more than single copy of RB1 by copy number data before C1D
- •Note: This molecular pre-screening will be centralized at at the CGH platform of Centre Léon Bérard (CLB).
- •Note: This molecular pre-screening will be centralized at the CGH platform of Centre Léon Bérard (CLB).
- •Note: This molecular pre-screening can be performed for patient without documented disease progression (PD) but study drug treatment cannot be initiated until confirmed radiological PD.
- •HPV negative tumor status must be documented before C1D
- •Note: This analysis will be centralized and performed by translational Biopathology platform of CLB during molecular pre-screening by IHC for p
- •Documented radiological progression or relapse after at least platin and cetuximab or anti-EGFR-based chemotherapy (combination or sequential treatment) and other standard treatment available at time of C1D1..
Exclusion Criteria
- •Cancer disease considered curable with surgery or radiotherapy.
- •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 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).
- •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).
- •Persisting significant toxicities related to prior treatments i.e. ≥ Grade 2 AE according to CTCAE V5.0 except alopecia (any grade), grade 2 peripheral neuropathy and biological values as defined in inclusion criteria.
- •Hypersensitivity to the active substance or excipient of study drug.
- •Have received prior treatment with any CDK4/6 inhibitor (or participated in any CDK4/6 inhibitor clinical trial for which treatment assignment is still blinded).
- •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.
Arms & Interventions
Abemaciclib
Intervention: Abemaciclib
Outcomes
Primary Outcomes
The 8-week non-progression rate defined as the rate of patients with complete response (CR), partial response (PR) or stable disease (SD) lasting at least 8 weeks, according to RECIST v1.1
Time Frame: 8 weeks after start of treatment
Secondary Outcomes
- 8-week Objective response rate(8 weeks after start of treatment)
- Overall Survival(12 months after start of treatment)
- Duration of response(12 months after start of treatment)
- Time to progression(12 months after start of treatment)
- Time to Treatment failure(12 months after start of treatment)
- Progression Free survival(12 months after start of treatment)
- Best response rate(12 months after start of treatment)