Nab-paclitaxel with Cisplatin or Cetuximab in Treating Patients with Stage III-IVb Head and Neck Cancer
This phase II trial studies how well nab-paclitaxel with cisplatin or cetuximab works in treating patients with stage III-IVb head and neck cancer. Drugs used in chemotherapy, such as nab-paclitaxel and cisplatin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cetuximab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Giving monoclonal antibody therapy with chemotherapy may kill more cancer cells than chemotherapy alone.
Inclusion Criteria
- ARM 1 and 3 - AP
- Diagnosis of selected stage III or IVa/b head and neck squamous cell carcinoma (HNSCC); Arm 1: T2-T4 primary tumors; Arm 3: T1-T4 primary tumors; although most of these patients will have regional nodal disease, patients with no nodal disease will also be eligible
- Arm 1: Presence of disease at the oropharynx, hypopharynx, or larynx sub-sites
- Arm 3: Presence of disease at the oropharynx sub-sites, which is HPV-related as verified by p16, a surrogate marker of HPV, or HPV in situ hybridization (ISH) or polymerase chain reaction (PCR)
- Presence of measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with CT scan
- At least 18 years of age
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 3 months after completing treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
- Able to understand and willing to sign an Institutional Review Board (IRB)-approved written informed consent document
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- Absolute neutrophil count (ANC): >= 1500/mcL
- Platelets: > 100,000/mcL
- Hemoglobin > 9.0 g/dL
- Total bilirubin =< 1.5 mg/dL
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/alkaline phosphatase: =< 2.5 x upper limit of normal (ULN)
- Serum creatinine: < 1.5 mg/dL or calculated glomerular filtration rate (GFR) >= 75 cc/min; creatinine clearance (CrCl) by Cockcroft Gault will be used to estimate GFR
- Pulmonary: no requirement for supplemental oxygen and no evidence of moderate-severe chronic obstructive pulmonary disease (COPD) by pulmonary function tests (PFTs)
- ARM 2 - A: Diagnosis of selected stage III or IVa/b HNSCC; T2-T4 primary tumors (patients with T1 tumors will be excluded); although most of these patients will have regional nodal disease, patients with no nodal disease will also be eligible
- ARM 2 - A: Presence of disease at the oropharynx, hypopharynx, or larynx sub-sites
- ARM 2 - A: Presence of measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with CT scan
- ARM 2 - A: At least 18 years of age
- ARM 2 - A: Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 3 months after completing treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
- ARM 2 - A: Able to understand and willing to sign an IRB-approved written informed consent document
- ARM 2 - A: ECOG performance status =< 3
- ARM 2 - A: ANC: >= 1500/mcL
- ARM 2 - A: Platelets: >= 100,000/mcL
- ARM 2 - A: Hemoglobin > 9.0 g/dL
- ARM 2 - A: Total bilirubin =< 2.0 mg/dL
- ARM 2 - A: AST/ALT/alkaline phosphatase: =< 5 x ULN
- ARM 2 - A: Calculated GFR > 30 cc/min; creatinine clearance (CrCl) by Cockcroft Gault will be used to estimate GFR
- ARM 2 - A: Pulmonary: patients with a requirement for supplemental oxygen or evidence of moderate-severe COPD by PFTs are permitted to enroll
- If a patient fully meets criteria for Arm 1, but has profound hearing loss and the physician feels that the patient should not receive cisplatin, the patient will be eligible for Arm 2
- If a patient fully meets criteria for Arm 1, but has a history of solid organ or bone marrow transplant, the patient will be eligible for Arm 2 (due to contraindications of cisplatin with medications the patient is taking due to the transplant)
Exclusion Criteria
- Prior chemotherapy, prior epidermal growth factor receptor (EGFR) targeted therapy, or prior radiation therapy for HNSCC
- Disease at the nasopharyngeal, sinus, oral cavity, or other sub-site not specified
- Diagnosis of unknown primary squamous cell carcinoma of the head and neck
- History of prior invasive malignancy diagnosed within 3 years prior to study enrollment; exceptions are malignancies with a negligible risk of metastasis or death (e.g., expected 5-year OS > 90%) that were treated with an expected curative outcome, such as squamous cell carcinoma of the skin, in-situ carcinoma of the cervix uteri, non-melanomatous skin cancer, carcinoma in situ of the breast, or incidental histological finding of prostate cancer (TNM stage of T1a or T1b)
- Receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the agents used in this study
- Taking cimetidine or allopurinol; if currently taking either of these medications, patient must discontinue for one week before receiving treatment with nab-paclitaxel
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or serious psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant and/or breastfeeding; a negative serum or urine pregnancy test is required at screening for all female patients of childbearing potential
- Known to be human immunodeficiency virus (HIV)-positive on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with the study agents; in addition, these patients are at increased risk of lethal infections when treated with marrow suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
- Peripheral neuropathy > grade 1
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02573493.
PRIMARY OBJECTIVES:
I. To determine the complete response (CR) rate by clinical exam at the primary tumor site following two cycles of Arm 1: nab-paclitaxel and cisplatin (AP) or Arm 2: nab-paclitaxel alone (A) given over 6 weeks (with the objective to have each arm non-inferior to the primary tumor site [PTS] CR rate with nab-paclitaxel, cisplatin, fluorouracil [APF] [77%]). (Arms 1 and 2)
II. To determine the median percent weight loss in patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) who are treated with AP. (Arm 3)
SECONDARY OBJECTIVES:
I. To determine the complete response (CR) rate by clinical exam at the primary tumor site following two cycles of AP given over 6 weeks (with the objective to have it be non-inferior to the PTS CR rate with APF [77%]). (Arm 3)
II. To document the clinical partial response (PR) rate at the primary tumor site and the clinical CR and PR rates at the involved regional nodes following two cycles of Arm 1: AP or Arm 2: A, and Arm 3: AP (for HPV-related OPSCC).
III. To document the anatomic tumor response as assessed by computed tomography (CT) scan using Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 criteria following two cycles of Arm 1: AP or Arm 2: A, and Arm 3: AP (for HPV-related OPSCC).
IV. To document and quantify Ki-67 expression by immunohistochemistry (IHC) and histologic tumor response in primary tumor tissue obtained at baseline and following two cycles of AP or A and correlate these results with clinical primary tumor site response to Arm 1: AP or Arm 2: A, or Arm 3: AP (for HPV-related OPSCC).
V. To document and grade adverse events (AEs) with Arm 1: AP, Arm 2: A, or Arm 3: AP (for HPV-related OPSCC) and to compare to those observed with APF with the objective that Arm 1 will be at least 25% lower than the risk of grade 3-4 AEs during APF (40% decreased to 30%) and Arm 2 will be at least 50% lower than the risk of grade 3-4 AEs during APF (40% decreased to 20%).
VI. To determine the overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) of these patient populations.
VII. To document the measures of quality of life (QOL) at baseline, during treatment, and through one year after completion of treatment for all arms.
VIII. To compare response rate, OS, DFS, and PFS of Arm 3 to Arm 1 (stratified for HPV status).
IX. To compare the rate of grade 3-4 AEs during chemoradiation therapy (CRT) in Arm 3 to Arm 1.
X. To compare the median absolute and percent weight loss during CRT in Arms 2 and 3, to Arm 1.
OUTLINE: Patients are assigned to 1 of 3 treatment arms.
INDUCTION THERAPY:
ARM I AND III (AP): Patients receive nab-paclitaxel intravenously piggy back (IVPB) over 30 minutes on days 1, 8, and 15 and cisplatin IVPB over 60 minutes on day 1. Treatment repeats after 21 days for a second cycle. Patients achieving CR or PR at the primary tumor site and not showing disease progression may initiate a third cycle of induction therapy followed by radiation and concurrent cisplatin. Patients with stable disease (SD) or progressive disease (PD) proceed to surgery followed by CRT or radiation therapy and concurrent chemotherapy if not a candidate for surgery. Patients not meeting criteria for cisplatin may receive cetuximab.
ARM II (A): Patients receive 2 courses of nab-paclitaxel as in Arm I. Patients achieving CR or PR proceed to a third cycle followed by radiation and cetuximab. Patients with SD or PD proceed to surgery followed by CRT or directly to radiation therapy and concurrent chemotherapy if not a candidate for surgery.
RADIATION AND CONCURRENT CHEMOTHERAPY:
ARM I (AP): Patients receive cisplatin IVPB over 60 minutes on approximately days 1, 22, and 43 of radiation (1-35 days after completion of cycle 3) and undergo intensity-modulated radiation therapy (IMRT) 5 days per week for 7 weeks, beginning 21-42 days after the start of cycle 3.
ARM II (A): Patients receive cetuximab IVPB over 60 minutes (3 hours for dose 1) 1 week before the first day of definitive radiation therapy, and then weekly for 7 weeks concurrently with radiation therapy given as in Arm I.
ARM III (AP): Patients receive cisplatin IVPB over 60 minutes on day 1, 5 days before the first day of definitive radiation therapy (1-35 days after completion of cycle 3), or cetuximab IVPB over 60 minutes 7 days before the first day of definitive radiation therapy (1-35 days after completion of cycle 3) and weekly for 7 weeks concurrently with radiation therapy.
After completion of study treatment, patients are followed up at 2 weeks, 8 weeks, 16 weeks and 9, 12, 16, 20, 24, 28, 32, 36, 42, 48, 54, 60 months.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationSiteman Cancer Center at Washington University
Principal InvestigatorDouglas Ray Adkins
- Primary ID201510013
- Secondary IDsNCI-2015-01775
- ClinicalTrials.gov IDNCT02573493