Study of LEE011plus Cetuximab in Patients With a Cancer of the Head and Neck

NCT02429089 | Terminated Phase 1 DMC

• 1 other identifier: UCL-ONCO 2015-01
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 5

Brief Summary

In this trial, the investigators would like to investigate the activity of LEE011 associated with cetuximab (standard of care for the SCCHN patients at this stade of the disease).

Conditions

Squamous Cell Carcinoma of the Head and Neck

Keywords

recurrent; metastatic

Outcome Measures

Primary Outcomes (1)

• To determine the maximum tolerated dose

  Up to 20 months

Secondary Outcomes (1)

• To evaluate the toxicity profile (with CTCAE 4.03 scale)

  Up to 20 months

Study Arms (1)

Group I

EXPERIMENTAL

The patients will receive the same molecules (cetuximab and LEE011) but this phase I study will determine the DLTs by dose escalation of LEE011 (400 mg and 600mg).

Drug: LEE011

Interventions

LEE011 DRUG

The first 12 patients will receive cetuximab associated with LEE011 at doses of 400 mg and 600 mg daily to determine the DLTs and safety. In the expansion part, besides safety, objective response rate, progression-free survival and overall survival will be calculated with the inclusion of 14 patients.

Group I

Eligibility Criteria

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

You may qualify if:

• Recurrent and/or metastatic head and neck squamous cell carcinoma not amenable to curative treatment with surgery and/or chemotherapy and/or radiation.
• HPV negative tumors
• Previous treatment with anti-EGFR based therapy is allowed
• Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria (Tumor lesions previously irradiated or subjected to other locoregional therapy will only be considered measurable if disease progression at the treated site after completion of therapy is clearly documented).
• Progressive disease within 1 year after first line platinum-based chemotherapy given either as a part of the multimodal curative treatment or in the palliative setting or patients non-eligible for platinum therapy.
• Tumor easily accessible for a biopsy
• ECOG performance status 0-1, in stable medical condition
• Patients must have an expected survival of at least 3 months.
• Paraffin-embedded tumor tissue available for immunohistochemistry
• Patients must be over 18 years old and must be able to give written informed consent.
• Women of child-bearing age or sexually active female patients with reproductive potential must have a negative pregnancy test (serum or urine within the 7 days prior to enrollment).
• Patients able to swallow ribociclib capsules / tablets
• Patient has adequate bone marrow and organ function as defined by the following laboratory values :
• Absolute neutrophil count ≥ 1.5 × 109/L.
• Platelets ≥ 100 × 109/L.

You may not qualify if:

• Non-squamous head and neck cancer
• Nasopharynx cancer
• Patient who received any CDK4/6 inhibitor.
• Patient has a known hypersensitivity to any of the excipients of LEE011 (ribociclib) or combination drug
• Patient is concurrently using other anti-cancer therapy.
• Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered as major surgery).
• Patient who has not had resolution of all acute toxic effects of prior anti-cancer therapy to NCI CTCAE version 4.03 Grade \<1 (exception to this criterion: patients with any grade of alopecia are allowed to enter the study).
• Patient who has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug, and who has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia) and/or from whom ≥ 25% (R. E. Ellis 1961) of the bone marrow was irradiated.
• Patient has a concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
• Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:
• At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
• Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases.
• Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• Patient has a known history of HIV infection (testing not mandatory)
• Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections etc.)

Sponsors & Collaborators

• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: lead

Study Sites (5)

Grand Hôpital de Charleroi site Notre Dame

Charleroi, Hainaut, 6000, Belgium

Location

Hôpital de Jolimont

Haine-Saint-Paul, Hainaut, 7100, Belgium

Location

Cliniques universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Clinique et Maternité Sainte-Elisabeth

Namur, 5000, Belgium

Location

Related Publications (1)

• Seront E, Schmitz S, Papier M, van Maanen A, Henry S, Lonchay C, Rottey S, van Caloen G, Machiels JP. Phase 1 Study Evaluating the Association of the Cyclin-Dependent Kinase 4/6 Inhibitor Ribociclib and Cetuximab in Recurrent/Metastatic p16-Negative Squamous Cell Carcinoma of the Head and Neck. Front Oncol. 2019 Mar 19;9:155. doi: 10.3389/fonc.2019.00155. eCollection 2019.

  PMID: 30941307 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Recurrence; Neoplasm Metastasis

Interventions

ribociclib

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Study Officials

• Institut Roi Albert II Cliniques universitaires Saint-Luc

  Institut Roi Albert II, Cliniques universitaires Saint-Luc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2015
• First Posted: April 29, 2015
• Study Start: April 1, 2015
• Primary Completion: September 1, 2017
• Study Completion: September 1, 2018
• Last Updated: January 9, 2020

Record last verified: 2020-01

Locations

BE (5)