Clinical trial NCT01445405 (phase 1, status: completed)
Conditions: carcinoma, squamous, head and neck cancer, oral cancer, laryngeal cancer, pharyngeal cancer
ICD codes: C76.0, C47.0, C49.0, C77.0, D17.0, D21.0, D36.11
Drugs: bortezomib (velcade, ps-341), cetuximab, cisplatin
SMILES: CC(C)C[C@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)C1=CN=CC=N1)B(O)O, [H][C@]12SCC(COC(C)=O)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\C1=CSC(N)=N1)C(O)=O, [H][C@@]12N(C)C3=CC(OC)=C(C=C3[C@@]11CCN3CC=C[C@](CC)([C@@]13[H])[C@@]([H])(OC(C)=O)[C@]2(O)C(=O)OC)[C@]1(C[C@@]2([H])CN(CC(CC)=C2)CC2=C1NC1=CC=CC=C21)C(=O)OC
Eligibility criteria:

        -INCLUSION CRITERIA:

          1. Histologically or cytologically confirmed squamous cell carcinoma, including variants,
             or undifferentiated/poorly differentiated carcinoma of the head and neck (any site,
             except nasopharynx).

          2. Previously untreated stage IV disease (AJCC staging system, 6th edition), or,

          3. Patients with residual disease or regional recurrence of head and neck cancer after
             surgery and/or chemotherapy, but with no prior bortezomib, EGFR inhibitor therapy or
             head and neck radiotherapy. All such patients should be eligible to receive full dose
             radiation therapy, and must be evaluated and accepted for treatment by a Radiation
             Oncologist. Prior cisplatin is allowed if administered greater than 3 months earlier.

          4. Patients with no clinically measurable distant disease, or those with asymptomatic
             small distant lesions outside the radiation field of less than or equal to 3cm
             individual or aggregate diameter, but for whom palliation of local and regional
             disease is clinically warranted will be eligible.

          5. Any number of other prior systemic therapies is allowed. Patients must have fully
             recovered from the effects of any prior surgery, or chemotherapy. A minimum time
             period of 4 weeks (6 weeks for nitrosoureas or mitomycin C) should elapse between the
             completion of prior chemotherapy and enrollment in the study.

          6. Age greater than or equal to 18 years. Because no dosing or adverse event data are
             currently available on the use of bortezomib in combination with cetuximab or
             cisplatin and radiation in patients <18 years of age, and head and neck cancer in
             children is exceedingly rare, except for those with disorders of DNA damage repair,
             bone marrow or transplant immunosuppression likely to have lower tolerance to these
             drugs and RT, children are excluded from this study.

          7. ECOG performance status 0-1 (Karnofsky greater than or equal to 70 percent).

          8. Patients must have normal organ and marrow function as defined below:

               -  absolute neutrophil count greater than or equal to 1,500/mcL

               -  platelets greater than or equal to 100,000/mcL

               -  total bilirubin within normal institutional limits, except for patients with
                  Gilberts syndrome, with increased indirect bilirubin less than or equal to 3
                  mg/dL

               -  AST(SGOT)/ALT(SGPT) less than or equal to 2.5 times institutional upper limit of
                  normal

               -  creatinine within normal institutional limits

             OR

             -creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with
             creatinine levels above institutional normal.

          9. The effects of bortezomib on the developing human fetus are unknown. For this reason
             and because other therapeutic agents used in this trial are known to be teratogenic,
             women of child-bearing potential and men must have agreed to use adequate
             contraception (hormonal or barrier method of birth control; prior vasectomy; tubal
             ligation or abstinence) prior to study entry and for the duration of study
             participation. Should a woman become pregnant or suspect she is pregnant while
             participating in this study, she should inform her treating physician immediately.

         10. Adequate cognitive and neurologic function to protect against and detect and report
             toxicities experienced, and to understand and to sign a written informed consent
             document.

        EXCLUSION CRITERIA:

          1. Patients with previously untreated nasopharyngeal cancer (any stage) will be excluded,
             but patients with recurrent nasopharyngeal carcinoma will be eligible.

          2. Prior treatment with radiation to the head and neck, or systemic EGFR inhibitors or
             bortezomib is not allowed.

          3. Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or
             mitomycin C) prior to entering the study or those who have not recovered from adverse
             events due to agents administered more than 4 weeks earlier.

          4. Patients may not be receiving any other investigational agents.

          5. Patients with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events.

          6. History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to bortezomib, cetuximab, cisplatin or other agents used in study.

          7. Patients with greater than or equal to grade 2 peripheral sensory neuropathy because
             bortezomib can cause irreversible worsening and a painful type of chemotherapy
             associated peripheral neuropathy.

          8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          9. Pregnant women are excluded from this study because bortezomib, cetuximab and
             cisplatin have the potential for teratogenic or abortifacient effects. Because there
             is an unknown but potential risk for adverse events in nursing infants secondary to
             treatment of the mother with bortezomib, cetuximab and cisplatin, breastfeeding should
             be discontinued if the mother is treated with bortezomib, cetuximab and cisplatin.
             These potential risks may also apply to other agents used in this study.

         10. HIV-positive patients or patients on any antiretroviral therapy are ineligible because
             of the potential for possible pharmacodynamic interactions with bortezomib, cetuximab
             and cisplatin, particularly bone marrow and mucosal toxicity, which could affect the
             MTD. These patients are at increased risk of lethal infections when treated with
             marrow-suppressive therapy.