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Head and Neck NeoplasmsPhase 2NCT01566435

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

A Phase 2 study testing paclitaxel albumin-stabilized nanoparticle formulation, Cisplatin and Fluorouracil in people with Head and Neck Neoplasms, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Head and Neck Neoplasms
What is being tested?
paclitaxel albumin-stabilized nanoparticle formulation, Cisplatin and Fluorouracil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
9 Aug 2012to 31 Oct 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

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)

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.

Read the 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.

Being tested
paclitaxel albumin-stabilized nanoparticle formulation, Cisplatin, Fluorouracil, Intensity modulated radiation therapy, Cetuximab
Medical subject headings
Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • paclitaxel albumin-stabilized nanoparticle formulationDrug

    Also called ABI-007, Abraxane, Albumin-Stabilized Nanoparticle Paclitaxel, nab paclitaxel

  • CisplatinDrug

    Also called CACP, CDDP, CPDD, DDP

  • FluorouracilDrug

    Also called 5-fluorouracil, 5-Fluracil, 5-FU, Adrucil, Efudex, FU

  • Intensity modulated radiation therapyRadiation

    Also called IMRT

  • CetuximabDrug

    Also called Anti-EGFR Monoclonal Antibody, C225, C225 monoclonal antibody, IMC-C225, MOAB C225, monoclonal antibody C225

  • Quality-of-life assessmentProcedure or surgery

    Also called FACT H&N, FACT/GOG-NTX-4

    ACF baseline, IMRT baseline, Day 7, Week 12, months 6 and 12

Study groups in NCT01566435
Study groupRoleWhat they receive
Arm 1-ACF Induction Therapy Followed by Chemoradiation TherapyExperimentalACF 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
Receives: Drug: paclitaxel albumin-stabilized nanoparticle formulation; Drug: Cisplatin; Drug: Fluorouracil; Radiation: Intensity modulated radiation therapy; Drug: Cetuximab; Procedure: Quality-of-life assessment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Complete Response (CR) by Clinical Exam at Primary Tumor Site

    • Response will be assessed by laryngoscopy.
    • CR: disappearance of all lesions

    Measured: 6 weeks (2 cycles of therapy)

Secondary outcomes (13)

  1. Percentage of Participants With Partial Response (PR) at Primary Tumor Site

    • 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

    Measured: 6 weeks (2 cycles of therapy)

  2. Number of Participants Per Anatomic Tumor Response by CT Scan

    • 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.

    Measured: 6 weeks (2 cycles of therapy)

  3. Metabolic Tumor Responses as Measured by FDG-PET/CT

    • 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

    Measured: 6 weeks (2 cycles of therapy)

  4. Overall Survival Rate

    -Overall survival rate is the percentage of participants who are alive at 2 years.

    Measured: 2 years

  5. Adverse Events as Measured by Number of Participants That Experienced Each Common Adverse Event During ACF Induction Therapy

    Assessed by NCI-CTCAE version 3

    Measured: From start of treatment through 30 days after end of treatment

  6. Changes in Secreted Protein Acidic and Rich in Cysteine (SPARC) Expression by Immunohistochemistry (IHC) in Primary Tumor Tissue

    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.

    Measured: 6 weeks (2 cycles of therapy)

  7. Complete Response (CR) or Partial Response (PR) at Regional (Neck) Nodes as Measured by Clinical Exam

    Measured: 6 weeks (2 cycles of therapy)

  8. Changes in Ki-67 Expression by Immunohistochemistry (IHC) in Primary Tumor Tissue

    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.

    Measured: 6 weeks (2 cycles of therapy)

  9. Disease-free Survival (DFS) Rate

    Measured: 2 years

  10. Progression-free Survival (PFS)

    -Progression: at least a 20% increase in the sum of the longest diameter (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.

    Measured: 2 years

  11. Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) Total Score

    • Includes 39 questions: 7 in physical well-being, 6 in emotional well-being, 7 in functional well-being, and 12 in head \& neck
    • Scored from 0 (not at all) to 4 (very much)
    • Higher scores indicated worse physical and emotional well-being and better social/family and functional well-being
    • The FACT-H\&N Total Score (range 0-148) measures the sum of the physical, social, emotional, functional, and HNCS domains
    • The maximum score of 148 reflects the best quality of life.

    Measured: Through one year after completion of treatment

  12. Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) FACT-G Total Score

    • Includes 39 questions: 7 in physical well-being, 6 in emotional well-being, 7 in functional well-being, and 12 in head \& neck
    • Scored from 0 (not at all) to 4 (very much)
    • Higher scores indicated worse physical and emotional well-being and better social/family and functional well-being
    • The FACT-G Total Score (range 0-108) measures the sum of the physical, social, emotional, and functional domains but excludes the HNCS domain
    • The maximum score of 108 reflects the best quality of life.

    Measured: Through end of chemoradiation

  13. Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) Trial Outcome Index (TOI)

    • Includes 39 questions: 7 in physical well-being, 6 in emotional well-being, 7 in functional well-being, and 12 in head \& neck
    • Scored from 0 (not at all) to 4 (very much)
    • Higher scores indicated worse physical and emotional well-being and better social/family and functional well-being
    • The FACT-H\&N TOI (range 0-96) measures the total score for the physical, functional, and HNCS domains but excludes the emotional and social domains
    • The maximum score of 96 reflects the best quality of life.

    Measured: Through end of chemoradiation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Mar 2012 (estimated)
  2. Study start9 Aug 2012
  3. Primary completion31 Oct 2013
  4. Study completion31 Oct 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01566435
Sponsor's protocol ID
201202113
Status last verified
Sep 2020
First submitted
27 Mar 2012
Last updated
1 Oct 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Adkins D, Ley J, Oppelt P, Gay HA, Daly M, Paniello RC, Jackson R, Pipkorn P, Rich J, Zevallos J, Trinkaus K, Thorstad W. Impact on Health-Related Quality of Life of Induction Chemotherapy Compared With Concurrent Cisplatin and Radiation Therapy in Patients With Head and Neck Cancer. Clin Oncol (R Coll Radiol). 2019 Sep;31(9):e123-e131. doi: 10.1016/j.clon.2019.05.007. Epub 2019 May 28.

    PubMed 31147146

  • Adkins D, Ley J, Oppelt P, Wildes TM, Gay HA, Daly M, Rich J, Paniello RC, Jackson R, Pipkorn P, Nussenbaum B, Trinkaus K, Thorstad W. nab-Paclitaxel-based induction chemotherapy with or without cetuximab for locally advanced head and neck squamous cell carcinoma. Oral Oncol. 2017 Sep;72:26-31. doi: 10.1016/j.oraloncology.2017.07.001. Epub 2017 Jul 8.

    PubMed 28797458

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing paclitaxel albumin-stabilized nanoparticle formulation, Cisplatin and Fluorouracil in people with Head and Neck Neoplasms, run by Washington University School of Medicine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Complete Response (CR) by Clinical Exam at Primary Tumor Site (time frame: 6 weeks (2 cycles of therapy)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01566435, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2020.

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