Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Carboplatin Followed By Chemoradiation in Treating Patients With Recurrent Head and Neck Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by University of Chicago
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Chicago
ClinicalTrials.gov Identifier:
NCT01847326
First received: April 19, 2013
Last updated: March 12, 2014
Last verified: March 2014
  Purpose

This phase I trial studies the side effects and best dose of paclitaxel albumin-stabilized nanoparticle formulation when given together with carboplatin followed by chemoradiation in treating patients with recurrent head and neck cancer. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, carboplatin, fluorouracil, and hydroxyurea, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving paclitaxel albumin-stabilized nanoparticle formulation followed by chemoradiation therapy may be an effective treatment for head and neck cancer.


Condition Intervention Phase
Recurrent Salivary Gland Cancer
Recurrent Squamous Cell Carcinoma of the Hypopharynx
Recurrent Squamous Cell Carcinoma of the Larynx
Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
Recurrent Squamous Cell Carcinoma of the Nasopharynx
Recurrent Squamous Cell Carcinoma of the Oropharynx
Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Recurrent Verrucous Carcinoma of the Larynx
Recurrent Verrucous Carcinoma of the Oral Cavity
Salivary Gland Squamous Cell Carcinoma
Tongue Cancer
Drug: carboplatin
Drug: paclitaxel albumin-stabilized nanoparticle formulation
Drug: fluorouracil
Drug: hydroxyurea
Procedure: therapeutic conventional surgery
Radiation: radiation therapy
Radiation: hyperfractionated radiation therapy
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Nab-Paclitaxel-based Re-induction Chemotherapy Followed by Response-stratified Chemoradiotherapy in Patients With Previously Treated Squamous Cell Carcinoma of the Head and Neck.

Resource links provided by NLM:


Further study details as provided by University of Chicago:

Primary Outcome Measures:
  • Recommended phase II dose of paclitaxel albumin-stabilized nanoparticle formulation in combination with fluorouracil, hydroxyurea, and radiation therapy, determined according to incidence of DLT graded using the National Cancer Institute (NCI) CTCAE 4.0 [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • Recommended phase II dose of paclitaxel albumin-stabilized nanoparticle formulation in combination with radiation therapy, determined according to incidence of DLT graded using the NCI CTCAE 4.0 [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • PFS [ Time Frame: The time from the date of registration to the date of progressive disease or death, assessed up to 1 year ] [ Designated as safety issue: No ]
    Statistical significance will be determined by a two-sided P value =< 0.05. Progression-free survival curves will be calculated using the Kaplan-Meier method, and median progression-free survival time, along with 90% confidence intervals will be derived using the procedure described in Brookmeyer and Crowley.

  • Overall survival [ Time Frame: The time from the date of registration to the date of death, assessed up to 1 year ] [ Designated as safety issue: No ]
    Statistical significance will be determined by a two-sided P value =< 0.05. Overall survival curves will be calculated using the Kaplan-Meier method, and median overall survival time, along with 90% confidence intervals will be derived using the procedure described in Brookmeyer and Crowley.

  • Objective response rate (complete response [CR] + partial response [PR]) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    The objective response rate (CR + PR) and associated 90% confidence interval will be determined.


Estimated Enrollment: 61
Study Start Date: March 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (induction therapy and AFHX or AXX)
See Detailed Description
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: paclitaxel albumin-stabilized nanoparticle formulation
Given IV
Other Names:
  • ABI-007
  • nab paclitaxel
  • nab-paclitaxel
  • nanoparticle albumin-bound paclitaxel
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Drug: hydroxyurea
Given PO
Other Names:
  • HU
  • HYD
  • Hydrea
  • Hydroxycarbamide
  • Hydurea
Procedure: therapeutic conventional surgery
Undergo surgical resection
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Radiation: hyperfractionated radiation therapy
Undergo hyperfractionated radiation therapy
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) when given in combination with FHX (5 fluorouracil [fluorouracil], hydroxyurea and twice daily radiation, in good induction responders) and of nab-paclitaxel added to hypofractionated radiotherapy for poor responders.

II. To explore the feasibility of a more rapid palliative chemoradiotherapy approach inpatients with refractory disease as demonstrated by failure to respond to initial chemotherapy.

III. To explore the role of induction chemotherapy as a predictive tool for definitive head and neck cancer management of previously treated patients.

SECONDARY OBJECTIVES:

I. Progression-free survival (PFS) (time to disease progression or death from any cause) on both study arms.

II. Overall survival and response rates in both arms.

TERTIARY OBJECTIVES:

I. To determine the correlation of secreted protein, acidic, cysteine-rich (SPARC) expression in head and neck cancer and response to therapy.

OUTLINE: This is a dose-escalation study of paclitaxel albumin-stabilized nanoparticle formulation.

RE-INDUCTION THERAPY (WEEKS 1-6): Patients receive paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) over 30 minutes on days 1 and 8 and carboplatin IV over 30 minutes on day 1. Courses repeat every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving good response undergo surgical resection and proceed to chemoradiation within 4-6 weeks.

AFHX REGIMEN: Patients achieving response to re-induction therapy receive hydroxyurea orally (PO) every 12 hours for 6 days (11 doses) beginning on day 0, fluorouracil IV continuously over 120 hours beginning on day 0, and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1. Patients also undergo radiation therapy twice daily (BID) on days 1-5. Courses repeat every 14 days for 5 weeks in the absence of disease progression or unacceptable toxicity.

PACLITAXEL + RADIATION (AXX) REGIMEN: Patients not achieving response to re-induction therapy receive paclitaxel albumin-stabilized nanoparticle formulation IV and undergo hypofractionated radiation therapy on day 1. Courses repeat every 7 days for 5 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up monthly for 3 months, every 3 months for 2 years, every 6 months for 2 years, and then yearly thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histological or cytological documentation of recurrent head and neck cancer requiring regional therapy
  • Recurrent or second primary, previously irradiated squamous cell carcinoma of the head and neck (SCCHN) without clinically measurably metastatic disease
  • Prior radiation therapy completed >= 4 months, and/or chemotherapy completed >= 1 month before study entry, and patient should have recovered from any adverse effects
  • Predominance of disease that is amenable to radiotherapy
  • Measurable disease prior to induction chemotherapy
  • Eastern Cooperative Oncology Group performance status of one or less
  • Life expectancy of greater than 12 weeks
  • Women of childbearing potential and sexually active males must use an effective contraception method during treatment and for three months after completing treatment
  • Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test at screening for patients of childbearing potential
  • Patients must have < grade 2 pre-existing peripheral neuropathy (per Common Terminology Criteria for Adverse Events [CTCAE])
  • Leukocyte >= 3,000/ul
  • Absolute neutrophil count >= 1,500/ul
  • Platelets >= 1000,000/ul
  • Total bilirubin =< 1.5 x institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x institutional upper limit of normal
  • Creatinine clearance (CrCl) > 45 mL/min

Exclusion Criteria:

  • Previously untreated patients with locoregional-only disease are not eligible
  • Patients who have had chemotherapy within 4 weeks prior to entering the study, or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients may not be receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical composition agents used in the study
  • Patients with pre-existing grade 2 or greater peripheral neuropathy, defined as sensory alteration or paresthesia (including tingling), interfering with function
  • Uncontrolled intercurrent illness including but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  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: NCT01847326

Locations
United States, Illinois
University of Chicago Comprehensive Cancer Center Recruiting
Chicago, Illinois, United States, 60637-1470
Contact: Victoria Villaflor    773-702-2825    vvillafl@medicine.bsd.uchicago.edu   
Principal Investigator: Victoria Villaflor         
Sponsors and Collaborators
University of Chicago
Investigators
Principal Investigator: Victoria Villaflor University of Chicago Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT01847326     History of Changes
Other Study ID Numbers: 12-1554, NCI-2012-02179
Study First Received: April 19, 2013
Last Updated: March 12, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government

Additional relevant MeSH terms:
Nose Neoplasms
Carcinoma, Squamous Cell
Carcinoma
Laryngeal Neoplasms
Oropharyngeal Neoplasms
Carcinoma, Verrucous
Nasopharyngeal Neoplasms
Paranasal Sinus Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Laryngeal Diseases
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Otorhinolaryngologic Diseases
Pharyngeal Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Nasopharyngeal Diseases
Nose Diseases
Paranasal Sinus Diseases
Carboplatin
Paclitaxel
Fluorouracil
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014