A phase I/II study of nab-paclitaxel, cisplatin and cetuximab with concurrent radiation therapy for local-regionally advanced head-and-neck squamous cell carcinoma
Current proposed study
Since taxanes have been widely used in HNSCC, Nab-Paclitaxel (Abraxane) has demonstrated activity in HNSCC and in small cell lung cancer and has better side effect profile as compared to (Cremophor EL) based paclitaxel and docetaxel as demonstrated in the breast cancer trials, and potentially better antitumor activity, it is of interest to further explore the use of Nab-Paclitaxel (Abraxane) in HNSCC.
We propose this phase I/II study to use weekly Nab-Paclitaxel (Abraxane), cisplatin and Cetuximab (Erbitux) (ACE) with concurrent radiation in local-regionally advanced HNSCC. There are no published human studies combining Nab-Paclitaxel (Abraxane) with radiation. We will first determine the maximum tolerated dose (MTD) using a 3 + 3 design, then will begin enrolling patients into the phase II component using Nab-Paclitaxel (Abraxane) at the MTD with cisplatin 20 mg/m2 and Cetuximab (Erbitux) 250 mg/m2 weekly concurrent with daily radiation.
Histologically proven (from primary lesion and/or lymph nodes) diagnosis of squamous cell carcinoma of the oropharynx, hypopharynx, or larynx;
3.1.2 Selected stage III or IV disease (T2N2-3M0, T3-4 any N M0);
3.1.3 No distant metastasis by chest x-ray (or Chest CT scan or PET/CT scan) within 6 weeks prior to registration;
3.1.4 Zubrod Performance Status 0-1;
3.1.5 Age > 18;
3.1.6 CT scan or MRI of the neck or PET/CT scan within 6 weeks prior to registration.
3.1.7 Adequate bone marrow function, defined as follows:
18.104.22.168 Absolute neutrophil count (ANC) > 1,500 cells/mm3 based upon CBC/differential obtained within 4 weeks prior to registration on study;
22.214.171.124 Platelets > 100,000 cells/mm3 based upon CBC/differential obtained within 4 weeks prior to registration on study;
126.96.36.199 Hemoglobin > 9.0 g/dl based upon CBC/differential obtained within 4 weeks prior to registration on study (Note: The use of transfusion or other intervention to achieve Hgb > 8.0 g/dl is acceptable.)
3.1.8 Adequate hepatic function, defined as follows:
188.8.131.52 Bilirubin < 1.5 mg/dl within 4 weeks prior to registration on study;
184.108.40.206 AST, ALT and alkaline phosphatase < 2.5 x the upper limit of normal within 4 weeks prior to registration on study;
3.1.9 Adequate renal function, defined as follows:
220.127.116.11 Serum creatinine < 1.5 mg/dl within 4 weeks prior to registration
18.104.22.168 Creatinine clearance (CC) >= 50 ml/min within 4 weeks prior to registration determined by 24-hour collection or estimated by Cockcroft-Gault formula:
CCr male = [(140 x age) x (wt in kg)]
[(Serum Cr mg/dl) x (72)]
CCr female = 0.85 x (CrCl male)
3.1.10 Other pretreatment evaluations include:
22.214.171.124 History/physical examination within 4 weeks prior to registration, including assessment of weight and weight loss in past 6 months;
126.96.36.199 Medical oncology examination to evaluate medical contraindications prior to start chemotherapy
188.8.131.52 Dental evaluation with management prior to start of radiation.
184.108.40.206 Nutrition evaluation with consideration of percutaneous endoscopy gastrotomy (PEG) tube placement
3.1.11 Patients must sign a study-specific informed consent form prior to study entry.
3.1.12 For persons of childbearing potential:
Sexually active women of childbearing potential must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized.
Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control.
All WOCBP MUST have a negative pregnancy test within 7 days prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study.
In addition, all WOCBP should be instructed to contact the Investigator immediately if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during study participation.
The Investigator must immediately notify Abraxis Bioscience in the event of a confirmed pregnancy in a patient participating in the study.