Induction Chemotherapy With ACF Followed by Chemoradiation Therapy for Adv. Head & Neck Cancer - Full Text View

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: nab-paclitaxel Drug: Cisplatin Drug: Fluorouracil Radiation: Chemoradiation 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:

MedlinePlus related topics: Cancer Head and Neck Cancer

Drug Information available for: Fluorouracil Cisplatin Paclitaxel

U.S. FDA Resources

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

Primary Outcome Measures:

CR by clinical exam at primary tumor site after two cycles of ACF [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
Response will be assessed by laryngoscopy.

Secondary Outcome Measures:

Comparison of CR at primary tumor site after ACF to historical CR after ACCF [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
A one-sample test for noninferiority will be used.
PR at primary tumor site and CR or PR at regional nodes after two cycles of ACF [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
Response will be assessed by laryngoscopy.
Anatomic tumor response by CT scan after two cycles of ACF [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
Response assessed using RECIST criteria version 1.0
Metabolic tumor response by FDG-PET/CT after two cycles of ACF [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
Response assessed using RECIST criteria version 1.0
Survival (OS, DFS and PFS) as a measure of response to ACF in patient population [ Time Frame: 10 years ] [ Designated as safety issue: No ]
Kaplan-Meier models will be used to estimate median (if the median is reached) and to estimate 1 and 2 year rates with 95% confidence intervals.
Document and grade adverse events (AE's) with ACF [ Time Frame: 5 months (during ACF and definitive therapy to 30 days after end of treatment) ] [ Designated as safety issue: Yes ]
Type and grade of toxicity assessed by NCI-CTCAE version 3; Compare AE rates with ACF to those with ACCF (historical data).
Changes in SPARC and Ki-67 expression [ Time Frame: 2 days (at baseline and Week 6) ] [ Designated as safety issue: No ]
Primary tumor biopsy; analyzed using IHC.
Quality of life [ Time Frame: 16 months ] [ Designated as safety issue: No ]
Assessed using questionnaires administered at 6 time points starting at baseline.

Estimated Enrollment:	30
Study Start Date:	April 2012
Estimated Study Completion Date:	July 2013
Estimated Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Treatment (ACF induction+chemoradiation	Drug: paclitaxel albumin-stabilized nanoparticle formulation Patients receive ACF induction therapy comprising 2 cycles of nab-paclitaxel IV on days 1, 8, and 15; cisplatin IV on day 1, and fluorouracil IV on days 1-3 of a 21 day cycle. Patients achieving CR/PR receive a third cycle of ACF. All patients then receive definitive radiation therapy with concomitant chemotherapy within 35 days of completing ACF. Definitive therapy consists of IMRT QD 5 times a week for 7 or 8 weeks with cisplatin IV on days 1, 22 and 43 with cetuximab IV once per week. Other Name: ABI-007, Abraxane, Albumin-Stabilized Nanoparticle Paclitaxel, nab paclitaxel, nab-paclitaxel, nanoparticle albumin-bound paclitaxel Drug: nab-paclitaxel nab-paclitaxel 100mg/m2 IV on days 1, 8, and 15 of a 21 day cycle, X 2 cycles. If patients achieve a CR/PR after 2 cycles they may receive a third cycle of ACF. Other Names: ABI-007 Abraxane Albumin-Stabilized Nanoparticle Paclitaxel nab paclitaxel nab-paclitaxel, nanoparticle Drug: Cisplatin Cisplatin 75mg/m2 IV on day 1 of a 21 day cycle, X 2 cycles Other Names: CACP CDDP CPDD DDP Neoplatin Drug: Fluorouracil Fluorouracil 750mg/m2 IV on days 1-3 of a 21 day cycle, X 2 cycles Other Name: 5-fluorouracil, 5-Fluracil, 5-FU, Adrucil, Efudex, FU Radiation: Chemoradiation Definitive radiation therapy with concomitant chemotherapy within 35 days of completing ACF. RT IMRT QD 5 times a week over 7 wks at 200 cGy fractions for a total dose of 7000 cGy with concomitant chemotherapy, Cisplatin 10mg/m2 Day 1, 22 and 43. Other Name: IMRT Radiation: Chemoradiation Definitive radiation therapy with concomitant chemotherapy within 35 days of completing ACF. RT IMRT QD 5 times a week over 7 wks at 200 cGy fractions for a total dose of 7000 cGy with concomitant chemotherapy, Cetuximab (for patients who cannot receive cisplatin) will be started 7 days (+/- 3 days) before starting RT IMRT. The initial (loading) dose of cetuximab 400 mg/m2 IVPB. Subsequently, cetuximab doses of 250 mg/m2 IVPB weekly. Other Name: IMRT 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

Arms

Assigned Interventions

Experimental: Treatment (ACF induction+chemoradiation

Drug: paclitaxel albumin-stabilized nanoparticle formulation

Patients receive ACF induction therapy comprising 2 cycles of nab-paclitaxel IV on days 1, 8, and 15; cisplatin IV on day 1, and fluorouracil IV on days 1-3 of a 21 day cycle. Patients achieving CR/PR receive a third cycle of ACF. All patients then receive definitive radiation therapy with concomitant chemotherapy within 35 days of completing ACF. Definitive therapy consists of IMRT QD 5 times a week for 7 or 8 weeks with cisplatin IV on days 1, 22 and 43 with cetuximab IV once per week.

Other Name: ABI-007, Abraxane, Albumin-Stabilized Nanoparticle Paclitaxel, nab paclitaxel, nab-paclitaxel, nanoparticle albumin-bound paclitaxel

Drug: nab-paclitaxel

nab-paclitaxel 100mg/m2 IV on days 1, 8, and 15 of a 21 day cycle, X 2 cycles. If patients achieve a CR/PR after 2 cycles they may receive a third cycle of ACF.

Other Names:

ABI-007
Abraxane
Albumin-Stabilized Nanoparticle Paclitaxel
nab paclitaxel
nab-paclitaxel, nanoparticle

Drug: Cisplatin

Cisplatin 75mg/m2 IV on day 1 of a 21 day cycle, X 2 cycles

Other Names:

CACP
CDDP
CPDD
DDP
Neoplatin

Drug: Fluorouracil

Fluorouracil 750mg/m2 IV on days 1-3 of a 21 day cycle, X 2 cycles

Other Name: 5-fluorouracil, 5-Fluracil, 5-FU, Adrucil, Efudex, FU

Radiation: Chemoradiation

Definitive radiation therapy with concomitant chemotherapy within 35 days of completing ACF.

RT IMRT QD 5 times a week over 7 wks at 200 cGy fractions for a total dose of 7000 cGy with concomitant chemotherapy, Cisplatin 10mg/m2 Day 1, 22 and 43.

Other Name: IMRT

Radiation: Chemoradiation

Definitive radiation therapy with concomitant chemotherapy within 35 days of completing ACF.

RT IMRT QD 5 times a week over 7 wks at 200 cGy fractions for a total dose of 7000 cGy with concomitant chemotherapy, Cetuximab (for patients who cannot receive cisplatin) will be started 7 days (+/- 3 days) before starting RT IMRT. The initial (loading) dose of cetuximab 400 mg/m2 IVPB. Subsequently, cetuximab doses of 250 mg/m2 IVPB weekly.

Other Name: IMRT

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

Eligibility

Ages Eligible for Study:	18 Years and older
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 myst be >= 18 years of age.
Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
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 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

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

Contacts

Contact: Douglas Adkins, M.D.

314-747-7402

dadkins@dom.wustl.edu

Locations

United States, Missouri
Washington University School of Medicine	Recruiting
St. Louis, Missouri, United States, 63110
Contact: Douglas Askins, M.D. 314-747-7402 dadkins@dom.wustl.edu
Sub-Investigator: Jason Diaz, M.D.
Sub-Investigator: Bruce Haughey, M.D.
Sub-Investigator: Brian Nussenbaum, M.D.
Sub-Investigator: Randall Paniello, M.D.
Sub-Investigator: Ravi Uppaluri, M.D.
Sub-Investigator: Konstantinos Arnaoutakis, M.D.
Sub-Investigator: Daniel Morgensztern, M.D.
Sub-Investigator: Timothy Panella, M.D.
Sub-Investigator: Tanya Wildes, M.D.
Sub-Investigator: Farrpkh Dehdashti, M.D.
Sub-Investigator: Barry Siegel, M.D.
Sub-Investigator: Hiram Gay, M.D.
Sub-Investigator: Wade Thorstad, M.D.
Sub-Investigator: James Lewis, M.D.

Sponsors and Collaborators

Washington University School of Medicine

Investigators

Principal Investigator:

Douglas Adkins, M.D.

Washington University School of Medicine

More Information

Additional Information:

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

No publications provided

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
Last Updated:	December 20, 2012
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Neoplasms
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Neoplasms by Site
Cisplatin
Fluorouracil
Paclitaxel
Antineoplastic Agents
Therapeutic Uses

Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on May 21, 2013