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Induction Chemotherapy With ACF Followed by Chemoradiation Therapy for Adv. Head & Neck Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01566435
First received: March 27, 2012
Last updated: April 27, 2016
Last verified: April 2016
  Purpose
This phase II trial studies the safety and effectiveness of an induction chemotherapy (ACF) consisting of paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel), cisplatin and fluorouracil followed by chemoradiation therapy in treating patients with stage III-IV squamous cell cancer of the head and neck. ACF may be an effective way to reduce or downgrade locally aggressive tumors, and improve the chance of eradication by chemoradiation.

Condition Intervention Phase
Head and Neck Neoplasms
Drug: paclitaxel albumin-stabilized nanoparticle formulation
Drug: Cisplatin
Drug: Fluorouracil
Radiation: Intensity modulated radiation therapy
Drug: Cetuximab
Procedure: Quality-of-life assessment
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Nab-Paclitaxel, Cisplatin, and 5-FU (ACF) as Induction Therapy Followed by Definitive Concurrent Chemoradiation for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (HNSCC)

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Percentage of Participants With Complete Response (CR) by Clinical Exam at Primary Tumor Site [ Time Frame: 6 weeks (2 cycles of therapy) ] [ Designated as safety issue: No ]
    • Response will be assessed by laryngoscopy.
    • CR: disappearance of all lesions


Secondary Outcome Measures:
  • Percentage of Participants With Partial Response (PR) at Primary Tumor Site [ Time Frame: 6 weeks (2 cycles of therapy) ] [ Designated as safety issue: No ]
    • Response will be assessed by laryngoscopy.
    • PR: at least 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter

  • Number of Participants Per Anatomic Tumor Response by CT Scan [ Time Frame: 6 weeks (2 cycles of therapy) ] [ Designated as safety issue: No ]
    • Response assessed using RECIST criteria version 1.0
    • Complete response: disappearance of all target lesions
    • Partial response: at least 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum longest diameter
    • Non-complete response/non-progression: persistence of one or more non-target lesion and/or maintenance of tumor marker level above the upper limits of normal.
    • Progression: at least a 20% increase in the sum of the LD of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

  • Metabolic Tumor Response by FDG-PET/CT [ Time Frame: 6 weeks (2 cycles of therapy) ] [ Designated as safety issue: No ]
    • Complete metabolic response (CMR): Complete resolution of all metabolically active target and non-target lesions, and no interval development of new lesions
    • Partial metabolic response (PMR): 20% or greater decrease in max SUV from baseline, no metabolic progression of non-target lesions and no new lesions and/or decrease in total number of non-target lesions, no new lesions
    • Stable metabolic disease (SMD) - does not qualify for CMR, PMR, or PMD
    • Progressive metabolic disease (PMD): development of one or more metabolically active lesions or 20% or greater increased in max SUV from baseline, new metabolically active lesions

  • Overall Survival Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    -Overall survival rate is the percentage of participants who are alive at 2 years.

  • Compare Adverse Events From This Regimen to the ACCF Regimen [ Time Frame: From start of treatment through 30 days after end of treatment ] [ Designated as safety issue: Yes ]
    Type and grade of toxicity assessed by NCI-CTCAE version 3

  • Changes in Secreted Protein Acidic and Rich in Cysteine (SPARC) Expression by Immunohistochemistry (IHC) in Primary Tumor Tissue [ Time Frame: 6 weeks (2 cycles of therapy) ] [ Designated as safety issue: No ]
    SPARC and Ki-67 expression will be assessed at this institution by IHC stains performed on clinically available tumor specimens (paraffin blocks). The specimens will be collected retrospectively from prior biopsies (pre treatment and following 2 cycles of ACF) that will have consisted of a minimum of two needle cores (16-18 gauge) or two small incisional/excisional pieces of tumor. These will have been placed in 2% buffered formalin and transported to the surgical pathology processing lab.

  • Quality of Life (QOL) [ Time Frame: Through one year after completion of treatment ] [ Designated as safety issue: No ]
    • Assessed using questionnaires administered at 6 time points starting at baseline.
    • 4 page questionnaire will assess physical, social, emotional, and functional well-being through questions designed specifically for patients with head and neck cancer.
    • An additional 4 question QOL survey will assess symptoms of peripheral neuropathy.

  • CR or PR at Regional Nodes [ Time Frame: 6 weeks (2 cycles of therapy) ] [ Designated as safety issue: No ]
  • Changes in Ki-67 Expression by Immunohistochemistry (IHC) in Primary Tumor Tissue [ Time Frame: 6 weeks (2 cycles of therapy) ] [ Designated as safety issue: No ]
    Ki-67 expression will be assessed at this institution by IHC stains performed on clinically available tumor specimens (paraffin blocks). The specimens will be collected retrospectively from prior biopsies (pre treatment and following 2 cycles of ACF) that will have consisted of a minimum of two needle cores (16-18 gauge) or two small incisional/excisional pieces of tumor. These will have been placed in 2% buffered formalin and transported to the surgical pathology processing lab.

  • Disease-free Survival (DFS) Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Progression-free Survival (PFS) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: August 2012
Estimated Study Completion Date: October 2023
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1-ACF Induction Therapy Followed by Chemoradiation Therapy

ACF Induction Therapy (Cycle 1 and Cycle 2 - each cycle is every 3 weeks)

  1. nab-Paclitaxel 100 mg/m^2 on Days 1, 8, and 15
  2. Cisplatin 75 mg/m^2 on Day 1
  3. 5-FU 750 mg/m^2 on Days 1-3

If patient has complete or partial response, he/she will receive an additional ACF cycle (cycle 3). If patient has stable disease or progressive disease will not receive the third cycle of ACF.

Definitive Therapy

  1. Cisplatin 100 mg/m^2 IV on Days 1, 22, and 43
  2. Intensity modulated radiation therapy (IMRT) 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 area considered to be at intermediate risk. Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 5600 cGy in 35 fractions.
  3. If patient cannot receive cisplatin then he/she will receive cetuximab 250 mg/m^2 IV week for 8 weeks
Drug: paclitaxel albumin-stabilized nanoparticle formulation
Other Names:
  • ABI-007
  • Abraxane
  • Albumin-Stabilized Nanoparticle Paclitaxel
  • nab paclitaxel
  • nab-paclitaxel, nanoparticle
Drug: Cisplatin
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
  • Neoplatin
Drug: Fluorouracil
Other Name: 5-fluorouracil, 5-Fluracil, 5-FU, Adrucil, Efudex, FU
Radiation: Intensity modulated radiation therapy
Other Name: IMRT
Drug: Cetuximab
Other Name: Anti-EGFR Monoclonal Antibody, C225, C225 monoclonal antibody, IMC-C225, MOAB C225, monoclonal antibody C225
Procedure: Quality-of-life assessment
ACF baseline, IMRT baseline, Day 7, Week 12, months 6 and 12
Other Names:
  • FACT H&N
  • FACT/GOG-NTX-4

Detailed Description:
Compared to the standard induction regimen of TPF (docetaxel, cisplatin, and 5-FU), the ACCF (nab-paclitaxel, cisplatin, cetuximab, and 5-FU) regimen included two therapeutic changes: nab-paclitaxel was substituted for docetaxel and cetuximab was added. The investigators propose to eliminate cetuximab from the ACCF regimen to isolate the treatment effects of nab-paclitaxel when given with cisplatin and 5-FU. The primary objective of the ACF proposal is to determine the complete (CR) rate by clinical examination at the primary tumor site following two cycles of ACF. An important secondary objective will be to compare the tumor response rates at the primary site following two cycles of ACF to our historical experience following two cycles of ACCF (protocol # ABX 218/HRPO# 08-0911). In addition, the investigators will compare adverse events (AEs) between patients who receive ACF to the historical group given ACCF. From these two comparisons, we aim to determine if either ACF or ACCF is superior based on a balance of efficacy (using the surrogate prognostic endpoint of CR rate at primary tumor site) and toxicity.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient must have selected stage III or IVa/b head and neck squamous cell carcinoma (HNSCC); all patients must have 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
  • Patient must have disease at the oropharynx, hypopharynx, larynx, or oral cavity sub-sites
  • Patient must have 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
  • Patient must be >= 18 years of age.
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Patient must have adequate bone marrow and organ function as defined below:

    • 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) =< 2.5 x upper limit of normal (ULN)
    • Alkaline phosphatase =< 2.5 x ULN
    • Serum creatinine < 1.8 mg/dL
  • 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
  • Patient must be able to understand and willing to sign an Institutional Review Board (IRB)-approved written informed consent document
  • Patient with uncontrolled diabetes or fasting blood glucose level of greater than 200 mg/dL will be eligible for enrollment but will not be evaluable for PET imaging

Exclusion Criteria:

  • Patient must not have had prior chemotherapy, prior epidermal growth factor receptor (EGFR) targeted therapy, or prior radiation therapy for HNSCC
  • Patient must not have disease at the nasopharyngeal, sinus, or other sub-site not specified in the inclusion criteria; patient must not have unknown primary squamous cell carcinoma of the head and neck
  • Patient must not have a history of prior invasive malignancy diagnosed within 3 years prior to study enrollment other than local stage non-melanoma skin cancer
  • Patient must not be receiving any other investigational agents
  • Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the agents used in this study
  • Patient must not be taking cimetidine or allopurinol. If currently taking either of these medications, patient must discontinue for one week before receiving treatment with nab-paclitaxel
  • Patient must not have an 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
  • Patient must not be pregnant and/or breastfeeding; a negative serum or urine pregnancy test is required at screening for all female patients of childbearing potential
  • Patient must not be 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
  • Patient must not have peripheral neuropathy > grade 1
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01566435

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Douglas Adkins, M.D. Washington University School of Medicine
  More Information

Additional Information:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01566435     History of Changes
Other Study ID Numbers: 201202113 
Study First Received: March 27, 2012
Results First Received: September 8, 2015
Last Updated: April 27, 2016
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Cisplatin
Paclitaxel
Albumin-Bound Paclitaxel
Cetuximab
Fluorouracil
Antibodies, Monoclonal
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 08, 2016