Cisplatin, Nab-Paclitaxel, and Cetuximab (CACTUX) in Patients With Incurable Head and Neck Squamous Cell Carcinoma

Study Overview
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Brief Summary
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The purpose of this research study is to look at the effect of a treatment regimen called CACTUX on head and neck cancer. The CACTUX regimen is a combination of three drugs called cisplatin, nab-paclitaxel, and cetuximab (although carboplatin may be given in place of cisplatin if participants have previously had problems receiving cisplatin). The use of nab-paclitaxel in this combination is different from routine care, in which a drug called 5FU is often given instead, but the investigators group has conducted previous research where the investigators incorporated nab-paclitaxel into routine treatment with cisplatin, 5FU, and cetuximab. The investigators are looking at the incidence of side effects with the CACTUX regimen as well as response of the disease and health status.

Official Title
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Phase 2 Single Arm Trial of Cisplatin, Nab-Paclitaxel, and Cetuximab (CACTUX) in Patients With Incurable Head and Neck Squamous Cell Carcinoma (HNSCC)

Conditions
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Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma, Cancer of the Head and Neck

Intervention / Treatment
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* Drug: nab-paclitaxel
* Drug: Cisplatin
* Drug: Carboplatin
* Biological: Cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed incurable HNSCC of the oral cavity, oropharynx, larynx, hypopharynx, and/or Level 1-3 neck node with non-skin SCC and unknown primary. Incurable is defined as metastatic disease or a local or regional recurrence in a previously irradiated site that is unresectable (or patient declines resection). 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, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam per RECIST 1.1. At least 18 years of age. ECOG performance status ≤ 1 Adequate hematologic, renal, and hepatic function as defined below: Leukocytes ≥ 3,000/mcL Absolute neutrophil count ≥ 1,500/mcl Platelets ≥ 100,000/mcl Total bilirubin ≤ 1.5 mg/dL AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN, alkaline phosphatase ≤ 2.5 x IULN, unless bone metastasis is present in the absence of liver metastasis Creatinine at or below IULN (males 0.7-1.30 mg/dl; females 0.6-1.10 mg/dl) OR Creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal At least 4 months since completion of curative therapy, if given previously. Availability of diagnostic tumor tissue specimens for correlative studies. 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. Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable). Exclusion Criteria: Prior systemic therapy for incurable disease. Grade 2 or higher peripheral neuropathy at screening. A history of other malignancy ≤ 2 years previous; 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, incidental finding of prostate cancer (TNM stage of T1a or T1b), or synchronous H&N primaries Currently receiving any other investigational agents. Known brain metastases. Patients with known brain metastases must 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. A history of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, nab-paclitaxel, or other agents used in the study. Previous grade 1 or 2 allergic reaction to cetuximab is permissible. 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. Pregnant and/or breastfeeding. Patient must have a negative pregnancy test within 72 hours of start of study treatment. Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with the study drugs. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CACTUX: nab-paclitaxel, cisplatin (or carboplatin), cetuximab<br>Up to 6 cycles of CACTUX may be given. The CACTUX regimen consists of: nab-paclitaxel given intravenously over 30 minutes on an outpatient basis on Days 1, 8, and 15 of each 21-day cycle followed by cisplatin given intravenously over 60 minutes on an outpatient basis OR carboplatin AUC5 given intravenously over 30 minutes on an outpatient basis on Day 1 of each 21-day cycle followed by cetuximab given intravenously on an outpatient basis of Days 1, 8, and 15 of each 21-day cycle Cisplatin or carboplatin may be given at the discretion of the investigator. After the completion of 6 cycles of CACTUX, maintenance therapy will be given and consists of: nab-paclitaxel given intravenously over 30 minutes on an outpatient basis on Days 1 and 8 of each 21-day cycle cetuximab given intravenously on an outpatient basis on Days 1, 8, and 15 of each 21-day cycle | Drug: nab-paclitaxel<br> <br> * Other names: Paclitaxel protein-bound;Drug: Cisplatin<br> <br> * Other names: DDP;Drug: Carboplatin<br> <br> * Other names: CBDCA;Biological: Cetuximab<br> <br> * Other names: Erbitux®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) - with first line therapy | PFS is defined as the time from randomization to first radiologic confirmation of disease progression, or death from any cause. | 8 months (estimated median length of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | OS is defined as the time from randomization to death. | Until death (estimated 24 months) | 
| Overall response rate | Overall response rate = complete response + partial response Evaluated using RECIST 1.1. | 8 months (estimated median length of treatment) | 
| Grade 3 and 4 adverse events | Adverse events will be recorded from the date of first dose of study drug (nab-paclitaxel) until 28 days after the last dose of study drug. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for all toxicity reporting. | 9 months (28 days from last dose of study drug with estimated median length of treatment of 8 months) | 
| Quality of life | Using the EORTC QLQ-C30, MDADI, FACT-H&N, and FACT/GOG-NTX-4. The EORTC-QLQ-C30 has a total score, one general QOL and one within the last week subscale, as well as a single overall general health item and a single overall QOL item. Scale is from 1-4 with 1 = not at all and 4 = very much on 28 questions. The scale is from 1-7 on 2 questions with 1 = very poor and 7 = excellent. The MDADI has 1 global dysphagia item, physical, function and emotional subscales and one summary scale, which is the sum of the 3 subscales rescaled to 0-100. The FACT instruments have four subscales (physical, social, emotional and functional), as well as 11-12 head and neck cancer-specific questions. The scale goes from 1-4 with 1 = not at all and 4 = very much. | Baseline, End of cycle 2, End of cycle 6, and End of treatment (estimated median length of treatment is 8 months) | 
| Progression-free survival (PFS) - with maintenance therapy | PFS on maintenance therapy is defined as time from first dose of maintenance therapy to first radiologic confirmation of disease progression, or death from any cause. | 8 months (estimated median length of treatment) | 
| Disease control | Disease control = complete response + partial response + stable disease Evaluated using RECIST 1.1 | 8 months (estimated median length of treatment) |