Status and phase
Conditions
Treatments
About
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).
Full description
In the mammalian cell cycle, entry into S phase is achieved by cyclin-dependent kinases 4 and 6 (CDK4/6), which activate a family of E2F transcription factors by phosphorylating and deactivating the retinoblastoma protein (pRb). LEE011 is an orally, highly selective small molecule inhibitor of CDK4/6 that potently induces G1 arrest with sub-micromolar IC50's in a variety of pRb-positive cancer cells. A recent study showed that an inhibitor of the CDK4-CCND1 complex showed promising results in SCCHN pre-clinical models. There is a strong rationale to investigate CDK inhibitors in this disease. In phase Ib/II study as a single agent, the major toxicities observed were Grade 3 and 4 fatigue (53.8%), nausea (50.8%), neutropenia (47.7%), anemia (37.1%), leukopenia (46.2%), thrombocytopenia (34.1%), diarrhea (32.6%), vomiting (34.8%), lymphocytes count decreased (30.3%), anorexia (21.2%), hyperglycemia (21.2%), constipation (19.7%), hypoalbuminemia (18.9%), dyspnea (18.2%) and cough (16.7%).
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
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 :
Signed informed consent prior to beginning protocol specific procedure.
Exclusion criteria
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:
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.)
Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:
On screening, inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF >450 msec (using Fridericia's correction). All as determined by screening ECG (mean of triplicate ECGs)
Patient with a Child-Pugh score B or C
Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to the start of the treatment (see Appendix 1 for details):
Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment.
• The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular)
Patient is currently receiving warfarin or other coumarin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed.
Participation in a prior investigational study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception throughout the study and for 8 weeks after study drug discontinuation. Highly effective contraception methods include:
Total abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
Male sterilization (at least 6 months prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient
Combination of any of the two following (a+b or a+c or b+c)
Note: Oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction.
Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.]
Sexually active males unless they use a condom during intercourse while taking the drug and for 30 days after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
Patient has a history of non-compliance to medical regimen or inability to grant consent.
Primary purpose
Allocation
Interventional model
Masking
21 participants in 1 patient group
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal