Clinical trial NCT02573493: Nab-Paclitaxel and Cisplatin or Nab-paclitaxel as Induction Therapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (HNSCC)
Official title: Phase II Non-Randomized Three Arm Trial of Induction Chemotherapy With Nab-Paclitaxel and Cisplatin (AP: Arms 1 and 3) or Single Agent Nab-paclitaxel (A: Arm 2) as Induction Therapy Followed by Definitive Concurrent Chemoradiation for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (HNSCC): "The APA Trial".
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Squamous Cell Carcinoma of the Head and Neck
Carcinoma, Squamous Cell of the Head and Neck
Cancer of Head and Neck
Cancer of the Head and Neck
Head and Neck Cancer
Neoplasms, Head and Neck
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2015-10-09
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Arm 1 and Arm 2: Clinical Complete Response Rate as Measured by Clinical Exam at the Primary Tumor Site
timeFrame: Completion of 2 cycles (approximately 6 weeks)
measure: Arm 3: Median Percent Weight Loss
timeFrame: Completion of treatment (estimated to be 11-15 weeks)
Secondary outcomes:
measure: Arms 1, 2, and 3: Clinical Partial Response Rate as Measured by Clinical Exam at the Primary Tumor Site
timeFrame: Completion of 2 cycles (approximately 6 weeks)
measure: Arms 1, 2 and 3: Clinical Complete Response Rate as Measured by Clinical Exam at the Involved Regional Nodes
timeFrame: Completion of 2 cycles (approximately 6 weeks)
measure: Arms 1, 2, and 3: Clinical Partial Response Rate as Measured by Clinical Exam at the Involved Regional Nodes
timeFrame: Completion of 2 cycles (approximately 6 weeks)
measure: Arms 1, 2, and 3: Anatomic Tumor Response as Assessed by CT Using RECIST 1.1 Criteria
timeFrame: Completion of 2 cycles (approximately 6 weeks)
measure: 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
timeFrame: Completion of 2 cycles (approximately 6 weeks)
measure: 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
timeFrame: 30 days after completion of treatment (estimated to be 15-25 weeks)
measure: Arms 1, 2, and 3: Mean Total Score as Measured by the FACT/GOG-NTX-4
timeFrame: Baseline and one year after completion of treatment (approximately 74 weeks)
measure: Arms 1, 2, and 3: Mean Total Score as Measured by FACT-H&N
timeFrame: Baseline and one year after completion of treatment (approximately 74 weeks)
measure: Arms 1, 2, and 3: Kaplan-Meier Estimate of Overall Survival (OS)
timeFrame: Through one year after completion of treatment (approximately 74 weeks)
measure: Arms 1, 2, and 3: Kaplan-Meier Estimate of Overall Survival (OS)
timeFrame: Through 2 years after completion of treatment (estimated to be 2 years and 22 weeks)
measure: Arms 1, 2, and 3: Kaplan-Meier Estimate of Disease-free Survival (DFS)
timeFrame: Through one year after completion of treatment (approximately 74 weeks)
measure: Arms 1, 2, and 3: Kaplan-Meier Estimate of Disease-free Survival (DFS)
timeFrame: Through 2 years after completion of treatment (estimated to be 2 years and 22 weeks)
measure: Arms 1, 2, and 3: Kaplan-Meier Estimate of Progression-free Survival (PFS)
timeFrame: Through one year after completion of treatment (approximately 74 weeks)
measure: Arms 1, 2, and 3: Kaplan-Meier Estimate of Progression-free Survival (PFS)
timeFrame: Through 2 years after completion of treatment (estimated to be 2 years and 22 weeks)
measure: Arm 3: Clinical Complete Response Rate as Measured by Clinical Exam at the Primary Tumor Site
timeFrame: Completion of 2 cycles (approximately 6 weeks)
measure: Arm 1 and Arm 3: Comparison of Response Rate
timeFrame: Completion of 2 cycles (approximately 6 weeks)
measure: Arm 1 and Arm 3: Comparison of the Rate of Grade 3/4 Adverse Events
timeFrame: 30 days after completion of treatment (estimated to be 15-25 weeks)
measure: Comparison of Median Absolute Weight Loss in Arms 2 and 3 to Arm 1
timeFrame: From start of radiation treatment through completion of radiation treatment (estimated to be 7 weeks)
measure: Comparison of Median Percent Weight Loss in Arms 2 and 3 to Arm 1
timeFrame: From start of radiation treatment through completion of radiation treatment (estimated to be 7 weeks)
measure: Arms 1, 2, and 3: Kaplan-Meier Estimate of Overall Survival (OS)
timeFrame: Up to 5 years after completion of treatment (estimated to be 5 years and 22 weeks)
measure: Arms 1, 2, and 3: Kaplan-Meier Estimate of Progression-free Survival (PFS)
timeFrame: Up to 5 years after completion of treatment (estimated to be 5 years and 22 weeks)
measure: Arms 1, 2, and 3: Kaplan-Meier Estimate of Disease-free Survival (DFS)
timeFrame: Through 5 years after completion of treatment (estimated to be 5 years and 22 weeks)
measure: Arm 1 and Arm 3: Kaplan-Meier Estimate of Overall Survival
timeFrame: Through 5 years after completion of treatment (estimated to be 5 years and 22 weeks)
measure: Arm 1 and Arm 3: Kaplan-Meier Estimate of Disease-free Survival
timeFrame: Through 5 years after completion of treatment (estimated to be 5 years and 22 weeks)
measure: Arm 1 and Arm 3: Kaplan-Meier Estimate of Progression-free Survival
timeFrame: Through 5 years after completion of treatment (estimated to be 5 years and 22 weeks)
Other outcomes:
Locations:
city: Westwood
country: United States
facility: The University of Kansas Cancer Center and Medical Pavilion
state: Kansas
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Sioux Falls
country: United States
facility: Sanford Cancer Center
state: South Dakota
Study officials:
affiliation: Washington University School of Medicine
name: Douglas Adkins, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Oppelt P, Ley J, Daly M, Rich J, Paniello R, Jackson RS, Pipkorn P, Liu J, Gay H, Palka K, Neupane P, Powell S, Spanos WC, Gitau M, Zevallos J, Thorstad W, Adkins D. nab-Paclitaxel and cisplatin followed by cisplatin and radiation (Arm 1) and nab-paclitaxel followed by cetuximab and radiation (Arm 2) for locally advanced head and neck squamous-cell carcinoma: a multicenter, non-randomized phase 2 trial. Med Oncol. 2021 Mar 8;38(4):35. doi: 10.1007/s12032-021-01479-w.