Nab-Paclitaxel and Cisplatin or Nab-paclitaxel as Induction Therapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (HNSCC)

Washington University School of Medicine96 enrolled

Overview

In this trial, the objectives are to determine the efficacy and toxicity of induction chemotherapy (IC) with nab-paclitaxel + cisplatin (Arm 1: AP) and with nab-paclitaxel (Arm 2: A) alone in patients with HNSCC, and to compare these data to nab-paclitaxel, cisplatin, and 5-FU (APF). The investigators also hypothesize that the high anti-tumor efficacy of nab-paclitaxel in HNSCC is due to the upregulation of macropinocytosis, a result of the frequent presence of Ras and PI3K (and epidermal growth factor receptor -EGFR) activation in this cancer. Amendment to Add Arm 3: In this amendment, the investigators retain the AP + concurrent chemoradiation therapy (CRT) backbone but de-escalate the dose of radiation therapy (RT) from 70 Gy to 42 Gy. The investigators also plan to administer one dose (vs three) of cisplatin during RT. This novel treatment approach will be evaluated in patients with HPV-related oropharyngeal squamous cell carcinoma (OPSCC) (Arm 3), a sub-group with a very favorable prognosis.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: Arms 1 and 3 - AP * Diagnosis of selected Stage III or IVa/b HNSCC. Arm 1: T2-T4 primary tumors. Arm 3: T2T1-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 ISH or 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 IRB-approved written informed consent document. * ECOG performance status ≤ 1. * Adequate bone marrow and organ function as defined below: * ANC: ≥ 1500/mcL. * Platelets: \> 100,000/mcL. * Hemoglobin \> 9.0 g/dL * Total bilirubin ≤ 1.5 mg/dL * AST/ALT/alkaline phosphatase: ≤ 2.5 x ULN. * Serum creatinine: \< 1.5 mg/dL or calculated GFR ≥ 75 cc/min. 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). Inclusion Criteria: 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. * Presence of disease at the oropharynx, hypopharynx, or larynx sub-sites. * 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 IRB-approved written informed consent document. * ECOG performance status \< 3. * Adequate bone marrow and organ function as defined below: * ANC: ≥ 1500/mcL. * Platelets: ≥ 100,000/mcL. * Hemoglobin \> 9.0 g/dL * Total bilirubin ≤ 2.0 mg/dL * AST/ALT/alkaline phosphatase: ≤ 5x ULN. * Calculated GFR \>30 cc/min. CrCl by Cockcroft Gault will be used to estimate GFR. * 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 (Arm 1 and Arm 2) * Prior chemotherapy, prior EGFR targeted therapy, or prior radiation therapy for HNSCC. * Disease at the nasopharyngeal, sinus, oral cavity, or other sub-site not specified as eligible. * 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 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.

Locations (3)

The University of Kansas Cancer Center and Medical Pavilion

Westwood, Kansas, United States

Washington University School of Medicine

St Louis, Missouri, United States

Sanford Cancer Center

Sioux Falls, South Dakota, United States

Outcomes

Primary Outcomes

Arm 1 and Arm 2: Clinical Complete Response Rate as Measured by Clinical Exam at the Primary Tumor Site

* Assessment of primary tumor site will be done by laryngoscopy performed in the office or in the operating room. The primary tumor response to the first two cycles of induction will be assessed using visual categorical response. The percent change from baseline will be dictated in the ear, nose, and throat (ENT) physician's clinical exam note. * Complete response = complete resolution - 100% decrease/minimal residual mucosal abnormality

Time frame: Completion of 2 cycles (approximately 6 weeks)

Arm 3: Median Percent Weight Loss

Time frame: Completion of treatment (estimated to be 11-15 weeks)

Secondary Outcomes

Arms 1, 2, and 3: Clinical Partial Response Rate as Measured by Clinical Exam at the Primary Tumor Site

* Assessment of primary tumor site will be done by laryngoscopy performed in the office or in the operating room. The primary tumor response to the first two cycles of induction will be assessed using visual categorical response. The percent change from baseline will be dictated in the ENT physician's clinical exam note. * Partial response - 99-50% decrease

Time frame: Completion of 2 cycles (approximately 6 weeks)

Arms 1, 2 and 3: Clinical Complete Response Rate as Measured by Clinical Exam at the Involved Regional Nodes

* The involved neck node response to the first two cycles of induction will be assessed using visual categorical response. The neck node measurements will be performed clinically by the treating medical oncology physician and dictated in his/her assessment note. * Complete response - complete resolution - 100% decrease/minimal residual mucosal abnormality

Time frame: Completion of 2 cycles (approximately 6 weeks)

Arms 1, 2, and 3: Clinical Partial Response Rate as Measured by Clinical Exam at the Involved Regional Nodes

Time frame: Completion of 2 cycles (approximately 6 weeks)

Arms 1, 2, and 3: Anatomic Tumor Response as Assessed by CT Using RECIST 1.1 Criteria

-Computed tomography (CT) scan (intravenous contrast preferred) to document and measure the extent of the primary tumor size and involved regional neck nodes. RECIST 1.1 will be used to determine response at the primary tumor site, at the involved regional neck nodes and the radiographic overall tumor response.

Time frame: Completion of 2 cycles (approximately 6 weeks)

Arms 1, 2, and 3: Document and Quantify Ki-67 Expression by IHC in Primary Tumor Tissue and Correlate With Clinical Primary Tumor Site Response

Time frame: Completion of 2 cycles (approximately 6 weeks)

Arms 1, 2, and 3: Number of Participants Who Experienced a Grade 3-4 Adverse Event as Measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0

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 AE's during APF (40% decreased to 30%) and Arm 2 will be at least 50% lower than the risk of Grade 3-4 AE's during APF (40% decreased to 20%).

Time frame: 30 days after completion of treatment (estimated to be 15-25 weeks)

Arms 1, 2, and 3: Mean Total Score as Measured by the FACT/GOG-NTX-4

-The FACT/GOG-NTX-4 questionnaire has 4 questions about neuropathy (numbness/tingling in hands/feet and discomfort in hands/feet) with answers ranging from 0 (Not at all) to 4 (Very Much). The total score ranges from 0 to 16. A lower score indicates less neuropathy symptoms.

Time frame: Baseline and one year after completion of treatment (approximately 74 weeks)

Arms 1, 2, and 3: Mean Total Score as Measured by FACT-H&N

-The FACT-H\&N has 5 domains with 39 items including physical well-being (PWB), social/family well being (SWB), emotional well-being (EWB), functional well-being (FWB), and head \& neck cancer (HNCS) with answers ranging from 0 (Not at all) to 4 (Very Much). The PWB subscale score ranges from 0-28. The SWB subscale score ranges from 0-28. The EWB subscale score ranges from 0-24. The FWB subscale score ranges from 0-28. The HNCS subscale score ranges from 0-40. To obtain the total score all subscales are added together. The total score ranges from 0-148 with a higher score indicating a better quality of life.

Time frame: Baseline and one year after completion of treatment (approximately 74 weeks)

Arms 1, 2, and 3: Kaplan-Meier Estimate of Overall Survival (OS)

OS: duration of time from date of diagnosis to late date alive or time of death from any cause.

Time frame: Through one year after completion of treatment (approximately 74 weeks)

Arms 1, 2, and 3: Kaplan-Meier Estimate of Overall Survival (OS)

OS: duration of time from date of diagnosis to last date alive or time of death from any cause.

Time frame: Through 2 years after completion of treatment (estimated to be 2 years and 22 weeks)

Arms 1, 2, and 3: Kaplan-Meier Estimate of Disease-free Survival (DFS)

DFS: duration of time from last date of treatment to time of disease progression or death from any cause.

Time frame: Through one year after completion of treatment (approximately 74 weeks)

Arms 1, 2, and 3: Kaplan-Meier Estimate of Disease-free Survival (DFS)

DFS: duration of time from last date of treatment to time of disease progression or death from any cause.

Time frame: Through 2 years after completion of treatment (estimated to be 2 years and 22 weeks)

Arms 1, 2, and 3: Kaplan-Meier Estimate of Progression-free Survival (PFS)

◦PFS: duration of time from date of diagnosis to time of disease progression or death from any cause, whichever occurs first.

Time frame: Through one year after completion of treatment (approximately 74 weeks)

Arms 1, 2, and 3: Kaplan-Meier Estimate of Progression-free Survival (PFS)

◦PFS: duration of time from date of diagnosis to time of disease progression or death from any cause, whichever occurs first.

Time frame: Through 2 years after completion of treatment (estimated to be 2 years and 22 weeks)

Arm 3: Clinical Complete Response Rate as Measured by Clinical Exam at the Primary Tumor Site

Time frame: Completion of 2 cycles (approximately 6 weeks)

Arm 1 and Arm 3: Comparison of Response Rate

-Stratified for HPV status

Time frame: Completion of 2 cycles (approximately 6 weeks)

Arm 1 and Arm 3: Comparison of the Rate of Grade 3/4 Adverse Events

Time frame: 30 days after completion of treatment (estimated to be 15-25 weeks)

Comparison of Median Absolute Weight Loss in Arms 2 and 3 to Arm 1

Time frame: From start of radiation treatment through completion of radiation treatment (estimated to be 7 weeks)

Comparison of Median Percent Weight Loss in Arms 2 and 3 to Arm 1

Time frame: From start of radiation treatment through completion of radiation treatment (estimated to be 7 weeks)

Arms 1, 2, and 3: Kaplan-Meier Estimate of Overall Survival (OS)

OS: duration of time from start of treatment to time of death from any cause

Time frame: Up to 5 years after completion of treatment (estimated to be 5 years and 22 weeks)

Arms 1, 2, and 3: Kaplan-Meier Estimate of Progression-free Survival (PFS)

◦PFS: duration of time from start of treatment to time of progression or death, whichever occurs first.

Time frame: Up to 5 years after completion of treatment (estimated to be 5 years and 22 weeks)

Arms 1, 2, and 3: Kaplan-Meier Estimate of Disease-free Survival (DFS)

Time frame: Through 5 years after completion of treatment (estimated to be 5 years and 22 weeks)

Arm 1 and Arm 3: Kaplan-Meier Estimate of Overall Survival

Time frame: Through 5 years after completion of treatment (estimated to be 5 years and 22 weeks)

Arm 1 and Arm 3: Kaplan-Meier Estimate of Disease-free Survival

Time frame: Through 5 years after completion of treatment (estimated to be 5 years and 22 weeks)

Arm 1 and Arm 3: Kaplan-Meier Estimate of Progression-free Survival

Time frame: Through 5 years after completion of treatment (estimated to be 5 years and 22 weeks)

Nab-Paclitaxel and Cisplatin or Nab-paclitaxel as Induction Therapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (HNSCC)

Overview

Conditions

Interventions

Eligibility

Locations (3)

Outcomes

Primary Outcomes

Secondary Outcomes