Cancer of Head and Neck, Cancer of the Head and Neck, Carcinoma, Squamous Cell of the Head and Neck, Head and Neck Cancer, Neoplasms, Head and Neck, Squamous Cell Carcinoma of the Head and Neck
Conditions
Brief summary
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.
Interventions
DRUGnab-Paclitaxel
DRUGCisplatin
BIOLOGICALCetuximab
RADIATIONIntensity-Modulated Radiation Therapy
Sponsors
Celgene Corporation
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Arm 1 and Arm 2: Clinical Complete Response Rate as Measured by Clinical Exam at the Primary Tumor Site | Completion of 2 cycles (approximately 6 weeks) | * 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 |
| Arm 3: Median Percent Weight Loss | Completion of treatment (estimated to be 11-15 weeks) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Arms 1, 2 and 3: Clinical Complete Response Rate as Measured by Clinical Exam at the Involved Regional Nodes | Completion of 2 cycles (approximately 6 weeks) | * 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 |
| Arms 1, 2, and 3: Clinical Partial Response Rate as Measured by Clinical Exam at the Involved Regional Nodes | Completion of 2 cycles (approximately 6 weeks) | * 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. * Partial response - 99%-50% decrease |
| Arms 1, 2, and 3: Anatomic Tumor Response as Assessed by CT Using RECIST 1.1 Criteria | Completion of 2 cycles (approximately 6 weeks) | -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. |
| 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 | 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 | 30 days after completion of treatment (estimated to be 15-25 weeks) | 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%). |
| Arms 1, 2, and 3: Mean Total Score as Measured by the FACT/GOG-NTX-4 | Baseline and one year after completion of treatment (approximately 74 weeks) | -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. |
| Arms 1, 2, and 3: Mean Total Score as Measured by FACT-H&N | Baseline and one year after completion of treatment (approximately 74 weeks) | -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. |
| Arms 1, 2, and 3: Kaplan-Meier Estimate of Overall Survival (OS) | Through one year after completion of treatment (approximately 74 weeks) | OS: duration of time from date of diagnosis to late date alive or time of death from any cause. |
| Arms 1, 2, and 3: Clinical Partial Response Rate as Measured by Clinical Exam at the Primary Tumor Site | Completion of 2 cycles (approximately 6 weeks) | * 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 |
| Arm 3: Clinical Complete Response Rate as Measured by Clinical Exam at the Primary Tumor Site | Completion of 2 cycles (approximately 6 weeks) | * 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 |
| Arm 1 and Arm 3: Comparison of Response Rate | Completion of 2 cycles (approximately 6 weeks) | -Stratified for HPV status |
| Arm 1 and Arm 3: Comparison of the Rate of Grade 3/4 Adverse Events | 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 | 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 | From start of radiation treatment through completion of radiation treatment (estimated to be 7 weeks) | — |
| Arm 1 and Arm 3: Kaplan-Meier Estimate of Overall Survival | 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 | 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 | Through 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) | Through one year after completion of treatment (approximately 74 weeks) | ◦PFS: duration of time from date of diagnosis to time of disease progression or death from any cause, whichever occurs first. |
| Arms 1, 2, and 3: Kaplan-Meier Estimate of Disease-free Survival (DFS) | Through one year after completion of treatment (approximately 74 weeks) | DFS: duration of time from last date of treatment to time of disease progression or death from any cause. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT * Six weeks of nab-paclitaxel (100 mg/m2/week) and cisplatin (75 mg/m2 days 1 and 22) followed by primary tumor site (PTS) assessment
* If complete response (CR)/partial response (PR), three more weeks of nab-paclitaxel and cisplatin followed by concurrent chemoradiation therapy (CRT)
* If \<PR, move directly to CRT if not surgical candidates.
* CRT includes cisplatin (if cannot receive cisplatin will receive cetuximab) which will begin 1 to 35 days after the completion of cycle 3. The first dose of cisplatin will be given during the initial 5 days of definitive radiation therapy, the second on approximately Day 22 of radiation, and the third on approximately Day 43 of radiation.
* It is strongly recommended that intensity-modulated radiation therapy (IMRT) begin within 21 to 42 days (no later than 56 days) after the start of cycle 3. The total dose will be 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to areas considered to be an intermediate risk. | 40 |
| Arm 2: Nab-Paclitaxel (A) + CRT * Six weeks of nab-paclitaxel (100 mg/m2/week) followed by primary tumor site (PTS) assessment
* If CR/PR, three more weeks of nab-paclitaxel followed by CRT
* If \<PR, move directly to CRT if not surgical candidates.
* CRT includes cetuximab and will begin 1 to 35 days after completion of cycle -Cetuximab will be started 7 days before starting definitive radiation therapy. The initial loading dose of cetuximab will be 400 mg/m\^2. Subsequently, cetuximab will be given weekly at a dose of 250 mg/m\^2 for seven additional doses concurrently with radiation therapy.
* It is strongly recommended that IMRT begin within 21 to 42 days (no later than 56 days) after the start of cycle 3. The total dose will be 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to areas considered to be an intermediate risk. | 40 |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT * 6 weeks of nab-paclitaxel and cisplatin (days 1 & 22) followed by primary tumor site assessment
* If CR/PR, cycle 3 of induction then 42Gy radiation, 1 dose of cisplatin or 6 doses cetuximab
* If SD/PD: undergo surgery if candidate followed by CRT with 42 Gy RT and abbreviated cisplatin or cetuximab or 70Gy RT and 3 cycles of cisplatin or 8 doses of cetuximab
* CRT includes Cisplatin and will begin 1-35 days after the completion of Cycle 3 of induction. Cisplatin will be given as 1 dose during the initial 5 days of definitive radiation therapy
* Strongly recommended that radiation therapy begin within 28-49 days (and no later than 56 days) after the start of Cycle 3. Intensity modulated radiation therapy is to be used exclusively for this study. | 15 |
| Not Enrolled in Any Arm -Determined to be not eligible after enrollment to study and was therefore not enrolled on any study arm. | 1 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Determined to not be eligible after enrollment | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Total | Not Enrolled in Any Arm | Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arm 2: Nab-Paclitaxel (A) + CRT |
|---|---|---|---|---|---|
| Age, Continuous | 57.5 years | 61 years | 62 years | 61 years | 65.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 95 Participants | 1 Participants | 15 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 11 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 32 Participants | 85 Participants | 1 Participants | 15 Participants | 37 Participants |
| Region of Enrollment United States | 40 participants | 96 participants | 1 participants | 15 participants | 40 participants |
| Sex: Female, Male Female | 4 Participants | 14 Participants | 1 Participants | 1 Participants | 8 Participants |
| Sex: Female, Male Male | 36 Participants | 82 Participants | 0 Participants | 14 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 40 | 0 / 15 | 0 / 34 | 0 / 42 | 0 / 15 | 9 / 40 | 21 / 40 | 4 / 15 |
| other Total, other adverse events | 40 / 40 | 40 / 40 | 15 / 15 | 34 / 34 | 42 / 42 | 15 / 15 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 6 / 40 | 6 / 40 | 2 / 15 | 9 / 34 | 6 / 42 | 2 / 15 | 0 / 40 | 1 / 40 | 1 / 15 |
Outcome results
Primary
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)
Population: Only participants enrolled in Arm 1 and Arm 2 are evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arm 1 and Arm 2: Clinical Complete Response Rate as Measured by Clinical Exam at the Primary Tumor Site | 28 Participants |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arm 1 and Arm 2: Clinical Complete Response Rate as Measured by Clinical Exam at the Primary Tumor Site | 8 Participants |
Primary
Arm 3: Median Percent Weight Loss
Time frame: Completion of treatment (estimated to be 11-15 weeks)
Population: Only participants enrolled in Arm 3 are evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arm 3: Median Percent Weight Loss | 6.7 percentage of weight loss |
Secondary
Arm 1 and Arm 3: Comparison of Response Rate
-Stratified for HPV status
Time frame: Completion of 2 cycles (approximately 6 weeks)
Population: Data was not collected for this outcome measure.
Secondary
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)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arm 1 and Arm 3: Comparison of the Rate of Grade 3/4 Adverse Events | 23 Participants |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arm 1 and Arm 3: Comparison of the Rate of Grade 3/4 Adverse Events | 4 Participants |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arm 1 and Arm 3: Comparison of the Rate of Grade 3/4 Adverse Events | 37 Participants |
| Arm 1 CRT: Cisplatin + Radiation Therapy | Arm 1 and Arm 3: Comparison of the Rate of Grade 3/4 Adverse Events | 4 Participants |
Secondary
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)
Population: 2 participants were excluded in Arm 3 because they received full dose radiation therapy instead of reduced dose radiation therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arm 1 and Arm 3: Kaplan-Meier Estimate of Disease-free Survival | 77.2 percentage of participants |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arm 1 and Arm 3: Kaplan-Meier Estimate of Disease-free Survival | 69.2 percentage of participants |
Secondary
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)
Population: 2 participants were excluded in Arm 3 because they received full dose radiation therapy instead of reduced dose radiation therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arm 1 and Arm 3: Kaplan-Meier Estimate of Overall Survival | 77.1 percentage of participants |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arm 1 and Arm 3: Kaplan-Meier Estimate of Overall Survival | 68.4 percentage of participants |
Secondary
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)
Population: 2 participants were excluded in Arm 3 because they received full dose radiation therapy instead of reduced dose radiation therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arm 1 and Arm 3: Kaplan-Meier Estimate of Progression-free Survival | 77.2 percentage of participants |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arm 1 and Arm 3: Kaplan-Meier Estimate of Progression-free Survival | 69.2 percentage of participants |
Secondary
Arm 3: 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)
Population: Only participants enrolled in Arm 3 are evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arm 3: Clinical Complete Response Rate as Measured by Clinical Exam at the Primary Tumor Site | 9 Participants |
Secondary
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)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arms 1, 2, and 3: Anatomic Tumor Response as Assessed by CT Using RECIST 1.1 Criteria | Complete response | 2 Participants |
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arms 1, 2, and 3: Anatomic Tumor Response as Assessed by CT Using RECIST 1.1 Criteria | Partial response | 22 Participants |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arms 1, 2, and 3: Anatomic Tumor Response as Assessed by CT Using RECIST 1.1 Criteria | Complete response | 1 Participants |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arms 1, 2, and 3: Anatomic Tumor Response as Assessed by CT Using RECIST 1.1 Criteria | Partial response | 20 Participants |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arms 1, 2, and 3: Anatomic Tumor Response as Assessed by CT Using RECIST 1.1 Criteria | Complete response | 1 Participants |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arms 1, 2, and 3: Anatomic Tumor Response as Assessed by CT Using RECIST 1.1 Criteria | Partial response | 13 Participants |
Secondary
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)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arms 1, 2 and 3: Clinical Complete Response Rate as Measured by Clinical Exam at the Involved Regional Nodes | 18 Participants |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arms 1, 2 and 3: Clinical Complete Response Rate as Measured by Clinical Exam at the Involved Regional Nodes | 14 Participants |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arms 1, 2 and 3: Clinical Complete Response Rate as Measured by Clinical Exam at the Involved Regional Nodes | 3 Participants |
Secondary
Arms 1, 2, and 3: Clinical Partial 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. * Partial response - 99%-50% decrease
Time frame: Completion of 2 cycles (approximately 6 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arms 1, 2, and 3: Clinical Partial Response Rate as Measured by Clinical Exam at the Involved Regional Nodes | 11 Participants |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arms 1, 2, and 3: Clinical Partial Response Rate as Measured by Clinical Exam at the Involved Regional Nodes | 14 Participants |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arms 1, 2, and 3: Clinical Partial Response Rate as Measured by Clinical Exam at the Involved Regional Nodes | 7 Participants |
Secondary
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)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arms 1, 2, and 3: Clinical Partial Response Rate as Measured by Clinical Exam at the Primary Tumor Site | 11 Participants |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arms 1, 2, and 3: Clinical Partial Response Rate as Measured by Clinical Exam at the Primary Tumor Site | 28 Participants |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arms 1, 2, and 3: Clinical Partial Response Rate as Measured by Clinical Exam at the Primary Tumor Site | 6 Participants |
Secondary
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)
Population: The data was not collected for this outcome measure.
Secondary
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)
Population: 2 participants were excluded in Arm 3 because they received full dose radiation therapy instead of reduced dose radiation therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Disease-free Survival (DFS) | 87.50 percentage of participants |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Disease-free Survival (DFS) | 62.50 percentage of participants |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Disease-free Survival (DFS) | 76.92 percentage of participants |
Secondary
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)
Population: 2 participants were excluded in Arm 3 because they received full dose radiation therapy instead of reduced dose radiation therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Disease-free Survival (DFS) | 87.50 percentage of participants |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Disease-free Survival (DFS) | 51.81 percentage of participants |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Disease-free Survival (DFS) | 69.23 percentage of participants |
Secondary
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 | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Disease-free Survival (DFS) | 77.2 percentage of participants |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Disease-free Survival (DFS) | 32.0 percentage of participants |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Disease-free Survival (DFS) | 69.2 percentage of participants |
Secondary
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)
Population: 2 participants were excluded in Arm 3 because they received full dose radiation therapy instead of reduced dose radiation therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Overall Survival (OS) | 100 percentage of particpants |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Overall Survival (OS) | 87.50 percentage of particpants |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Overall Survival (OS) | 92.31 percentage of particpants |
Secondary
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)
Population: 2 participants were excluded in Arm 3 because they received full dose radiation therapy instead of reduced dose radiation therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Overall Survival (OS) | 77.1 percentage of participants |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Overall Survival (OS) | 40.5 percentage of participants |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Overall Survival (OS) | 68.4 percentage of participants |
Secondary
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)
Population: 2 participants were excluded in Arm 3 because they received full dose radiation therapy instead of reduced dose radiation therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Overall Survival (OS) | 97.44 percentage of participants |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Overall Survival (OS) | 69.63 percentage of participants |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Overall Survival (OS) | 84.62 percentage of participants |
Secondary
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)
Population: 2 participants were excluded in Arm 3 because they received full dose radiation therapy instead of reduced dose radiation therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Progression-free Survival (PFS) | 87.43 percentage of participants |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Progression-free Survival (PFS) | 54.89 percentage of participants |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Progression-free Survival (PFS) | 69.23 percentage of participants |
Secondary
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)
Population: 2 participants were excluded in Arm 3 because they received full dose radiation therapy instead of reduced dose radiation therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Progression-free Survival (PFS) | 77.2 percentage of participants |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Progression-free Survival (PFS) | 33.8 percentage of participants |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Progression-free Survival (PFS) | 69.2 percentage of participants |
Secondary
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)
Population: 2 participants were excluded in Arm 3 because they received full dose radiation therapy instead of reduced dose radiation therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Progression-free Survival (PFS) | 92.50 percentage of participants |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Progression-free Survival (PFS) | 67.50 percentage of participants |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arms 1, 2, and 3: Kaplan-Meier Estimate of Progression-free Survival (PFS) | 76.92 percentage of participants |
Secondary
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)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arms 1, 2, and 3: Mean Total Score as Measured by FACT-H&N | Baseline | 2.02 score on a scale |
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arms 1, 2, and 3: Mean Total Score as Measured by FACT-H&N | End of treatment | 1.98 score on a scale |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arms 1, 2, and 3: Mean Total Score as Measured by FACT-H&N | Baseline | 1.86 score on a scale |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arms 1, 2, and 3: Mean Total Score as Measured by FACT-H&N | End of treatment | 1.82 score on a scale |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arms 1, 2, and 3: Mean Total Score as Measured by FACT-H&N | Baseline | 2.07 score on a scale |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arms 1, 2, and 3: Mean Total Score as Measured by FACT-H&N | End of treatment | 2.00 score on a scale |
Secondary
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)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arms 1, 2, and 3: Mean Total Score as Measured by the FACT/GOG-NTX-4 | Baseline | 0.19 score on a scale |
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Arms 1, 2, and 3: Mean Total Score as Measured by the FACT/GOG-NTX-4 | End of treatment | 1.55 score on a scale |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arms 1, 2, and 3: Mean Total Score as Measured by the FACT/GOG-NTX-4 | Baseline | 0.38 score on a scale |
| Arm 2: Nab-Paclitaxel (A) + CRT | Arms 1, 2, and 3: Mean Total Score as Measured by the FACT/GOG-NTX-4 | End of treatment | 0.91 score on a scale |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arms 1, 2, and 3: Mean Total Score as Measured by the FACT/GOG-NTX-4 | Baseline | 0.27 score on a scale |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Arms 1, 2, and 3: Mean Total Score as Measured by the FACT/GOG-NTX-4 | End of treatment | 1.54 score on a scale |
Secondary
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)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | 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 | 23 Participants |
| Arm 2: Nab-Paclitaxel (A) + CRT | 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 | 17 Participants |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | 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 | 4 Participants |
| Arm 1 CRT: Cisplatin + Radiation Therapy | 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 | 37 Participants |
| Arm 1 & 2 ERT: Cetuximab + Radiation Therapy | 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 | 35 Participants |
| Arm 3 CR: Cisplatin + Radiation Therapy | 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 | 4 Participants |
Secondary
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)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Comparison of Median Absolute Weight Loss in Arms 2 and 3 to Arm 1 | 8.4 kilograms |
| Arm 2: Nab-Paclitaxel (A) + CRT | Comparison of Median Absolute Weight Loss in Arms 2 and 3 to Arm 1 | 5.2 kilograms |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Comparison of Median Absolute Weight Loss in Arms 2 and 3 to Arm 1 | 7.0 kilograms |
Secondary
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)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT | Comparison of Median Percent Weight Loss in Arms 2 and 3 to Arm 1 | 9.1 median percent of weight loss |
| Arm 2: Nab-Paclitaxel (A) + CRT | Comparison of Median Percent Weight Loss in Arms 2 and 3 to Arm 1 | 6.6 median percent of weight loss |
| Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT | Comparison of Median Percent Weight Loss in Arms 2 and 3 to Arm 1 | 6.7 median percent of weight loss |