Clinical Trials /

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



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).

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:



Phase 1

Trial Eligibility



  • Brief Title: Study of LEE011plus Cetuximab in Patients With a Cancer of the Head and Neck
  • Official Title: Phase I Study of LEE011plus Cetuximab in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Clinical Trial IDs

  • ORG STUDY ID: UCL-ONCO 2015-01
  • NCT ID: NCT02429089


  • Squamous Cell Carcinoma of the Head and Neck


LEE011Group I


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).

Detailed 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%).

Trial Arms

Group IExperimentalThe 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).
  • LEE011

Eligibility Criteria

        Inclusion Criteria:

          1. Recurrent and/or metastatic head and neck squamous cell carcinoma not amenable to
             curative treatment with surgery and/or chemotherapy and/or radiation.

          2. HPV negative tumors

          3. Previous treatment with anti-EGFR based therapy is allowed

          4. 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).

          5. 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.

          6. Tumor easily accessible for a biopsy

          7. ECOG performance status 0-1, in stable medical condition

          8. Patients must have an expected survival of at least 3 months.

          9. Paraffin-embedded tumor tissue available for immunohistochemistry

         10. Patients must be over 18 years old and must be able to give written informed consent.

         11. 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).

         12. Patients able to swallow ribociclib capsules / tablets

         13. Patient has adequate bone marrow and organ function as defined by the following
             laboratory values :

               1. Absolute neutrophil count ≥ 1.5 × 109/L.

               2. Platelets ≥ 100 × 109/L.

               3. Hemoglobin ≥ 9 g/dl.

               4. Potassium, total calcium (corrected for serum albumin), magnesium, sodium and
                  phosphorus within normal limits for the institution or corrected to within limits
                  with supplements before first dose of study medication.

               5. INR ≤ 1.5.

               6. Serum creatinine ≤ 1.5 × mg/dL or creatinine clearance ≥50 mL/min.

               7. In the absence of liver metastases, Alanine aminotransferase (AST) and aspartate
                  aminotransferase (ALT) ≤ 2.5x ULN. If the patient has liver metastases, ALT and
                  AST < 5 x ULN.

               8. Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 x ULN or direct bilirubin
                  ≤1.5 x ULN in patients with well documented Gilbert's Syndrome.

         14. Signed informed consent prior to beginning protocol specific procedure.

        Exclusion Criteria:

          1. Non-squamous head and neck cancer

          2. Nasopharynx cancer

          3. Patient who received any CDK4/6 inhibitor.

          4. Patient has a known hypersensitivity to any of the excipients of LEE011 (ribociclib)
             or combination drug

          5. Patient is concurrently using other anti-cancer therapy.

          6. 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).

          7. 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).

          8. 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.

          9. 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.

         10. 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.

         11. 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

         12. Patient has a known history of HIV infection (testing not mandatory)

         13. 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.)

         14. Patient has active cardiac disease or a history of cardiac dysfunction including any
             of the following:

               -  History of acute coronary syndromes (including myocardial infarction, unstable
                  angina, coronary artery bypass grafting, coronary angioplasty or stenting) or
                  symptomatic pericarditis within 12 months prior to screening.

               -  History of documented congestive heart failure (New York Heart Association
                  functional classification III-IV)

               -  Documented cardiomyopathy

               -  Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by
                  Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)

               -  History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal
                  arrhythmias, or conduction abnormality in the previous 12 months of screening.

               -  On screening, any of the following cardiac parameters: bradycardia (heart rate <
                  50 at rest), tachycardia (heart rate > 90 at rest), PR interval > 220 msec, QRS
                  interval >109 msec, or QTcF >450 msec.

               -  Congenital long QT syndrome or family history of long QT syndrome

               -  Systolic blood pressure >160 or <90 mmHg at screening

               -  Bradycardia (heart < 50 at rest), by ECG or pulse, at screening

         15. 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)

         16. Patient with a Child-Pugh score B or C

         17. 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):

               -  That are known strong inducers or inhibitors of CYP3A4/5. including grapefruit,
                  grapefruit hybrids, pummelos, star-fruit, and Seville oranges

               -  That have a known risk to prolong the QT interval or induce Torsades de Pointes.

               -  That have a narrow therapeutic window and are predominantly metabolized through

               -  Herbal preparations/medications, dietary supplements

         18. 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)

         19. 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.

         20. Participation in a prior investigational study within 30 days prior to enrollment or
             within 5 half-lives of the investigational product, whichever is longer

         21. 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

               -  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

               -  Combination of any of the two following (a+b or a+c or b+c)

                    1. Use of oral, injected or implanted hormonal methods of contraception or
                       other forms of hormonal contraception that have comparable efficacy (failure
                       rate <1%), for example hormone vaginal ring or transdermal hormone

                    2. Placement of an intrauterine device (IUD) or intrauterine system (IUS)

                    3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
                       cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal
                       suppository In case of use of oral contraception, women should have been
                       stable on the same pill before taking study treatment.

             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.]

         22. 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.

         23. Patient has a history of non-compliance to medical regimen or inability to grant
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To determine the maximum tolerated dose
Time Frame:Up to 20 months
Safety Issue:

Secondary Outcome Measures

Measure:To evaluate the toxicity profile (with CTCAE 4.03 scale)
Time Frame:Up to 20 months
Safety Issue:


Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Trial Keywords

  • recurrent
  • metastatic

Last Updated

January 9, 2020