Evaluation 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

NCT03356223 | Completed Phase 2 DMC

• 1 other identifier: ET16-116 (ABORL)
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 3

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.

Conditions

Head and Neck Cancer; Advanced Cancer; Metastatic Cancer

Keywords

Clinical Trial; Phase II; Monotherapy; Abemaciclib; Homozygous deletion of CDKN2A; Amplification of CCND1; Amplification of CDK6; Multicenter Trial

Outcome Measures

Primary Outcomes (1)

• 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

  8 weeks after start of treatment

Secondary Outcomes (7)

• 8-week Objective response rate

  8 weeks after start of treatment

• Duration of response

  12 months after start of treatment

• Best response rate

  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

Study Arms (1)

Abemaciclib

EXPERIMENTAL

Drug: Abemaciclib

Interventions

Abemaciclib DRUG

400mg/day with 2 doses of 200mg 12-hour apart For each 28-day cycle, a total of 56 doses of study drug will be dispensed. Route of administration : oral Duration of treatment until the patient experiences an unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent.

Abemaciclib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 pre-screening: either an archival tumor block or a dedicated freshly collected tumor biopsy.
• I4. 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 C1D1.
• 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.
• 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 pre-screening by IHC for p16.
• I6. 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..
• I7. At least one measurable lesion by CT-scan as per RECIST 1.1.
• I8. At least one biopsiable tumor lesion before C1D1 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 by the following tests (to be checked using medical records and then carried out within 7 days prior C1D1):

You may not qualify if:

• 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).
• NI6. Hypersensitivity to the active substance or excipient of study drug.
• NI7. 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).
• NI8. Patient has received treatment with a drug that has not received regulatory approval for any indication within :
• days of C1D1 for non myelosuppressive agent or
• days of C1D1 for a myelosuppressive agent.
• NI9. Patient has had major surgery and/or radiotherapy 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.

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (3)

Hôpital Saint-André

Bordeaux, 33075, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Centre Antoine Lassagne

Nice, 06189, France

Location

Related Publications (14)

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  PMID: 25267748 BACKGROUND

MeSH Terms

Conditions

Head and Neck Neoplasms; Neoplasm Metastasis

Interventions

abemaciclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jérôme FAYETTE, MD

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2017
• First Posted: November 29, 2017
• Study Start: February 5, 2018
• Primary Completion: November 5, 2022
• Study Completion: December 5, 2022
• Last Updated: February 23, 2023

Record last verified: 2022-07

Locations

FR (3)