Trial of 2 Cycles of Induction Chemo With Abraxane, Cetuximab, Cisplatin, & 5-FU for Advanced Head and Neck Cancer - Full Text View

Sponsored by:	Washington University School of Medicine
Information provided by:	Washington University School of Medicine
ClinicalTrials.gov Identifier:	NCT00736944

Purpose

This phase two trial will determine the tumor response rate at the primary site and at involved regional nodes to two cycles of an IC regimen of weekly Abraxane and cetuximab given in combination with cisplatin and 5-FU in patients with local regionally advanced HNSCC.

Condition	Intervention	Phase
Squamous Cell Carcinoma of the Head and Neck	Drug: Abraxane Drug: Cetuximab Drug: Cisplatin Drug: 5-FU Radiation: Radiation (Post induction)	Phase II

MedlinePlus related topics: Cancer

Drug Information available for: Cisplatin Paclitaxel Fluorouracil Cetuximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Active Control, Single Group Assignment, Efficacy Study
Official Title:	Trial to Determine the CR Rate at the Primary Tumor Site After 2 Cycles of Induction Chemo With Abraxane, Cetuximab, Cisplatin, & 5-FU for Advanced Head & Neck Carcinoma Treated With Definitive Concurrent Cisplatin & Radiation Therapy

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

Primary Outcome Measures:

Determine the clinical complete response to the primary tumor [ Time Frame: tumor response ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Document the clinical Partial response to the primary tumor [ Time Frame: tumor response ] [ Designated as safety issue: No ]
Document the clinical complete and partial response to the involved regional nodes [ Time Frame: nodes response ] [ Designated as safety issue: No ]
Document the complete and partial response rates by FDG-PET scans [ Time Frame: treatment response ] [ Designated as safety issue: No ]
Document radiographic complete and partial response by CT scan [ Time Frame: treatment response ] [ Designated as safety issue: No ]
Correlate primary tumor site, nodal and overall tumor response rates based on WHO criteria of assessment with that based on CT scan and FDG-PET/CT. [ Time Frame: treatment response ] [ Designated as safety issue: No ]
Document and quantify SPARC expression by IHC in primary tumor tissue obtained at baseline in each patient and attempt to correlate these results with primary tumor site response to treatment. [ Time Frame: SPARC expression ] [ Designated as safety issue: No ]
Document and grade AE's with this induction chemotherapy regimen with a pre-planned safety analysis after the first ten patients have completed the induction chemotherapy regimen. [ Time Frame: completion of the first 10 patient's induciton chemotehrapy ] [ Designated as safety issue: Yes ]
Determine the overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) of this patient population. [ Time Frame: overall survival, disease free survival and progression free survival ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	October 2008
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Induction chemotherapy followed by Radiation therapy plus Cisplatin Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42.	Drug: Abraxane 100 mg/m2 IVPB, Day 1, 8 and 15 of cycles 1, 2, and 3 Drug: Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1 Drug: Cetuximab 250 mg IVPB, Day 8 and 15 cycle 1, Day 1, 8 and 15 of cycles 2 and 3 Drug: Cisplatin 75 mg/m2 IVPB Day 1, cycles 1, 2 and 3 Drug: 5-FU 750 mg/m2 CIVI Day 1, 2 and 3, cycles 1, 2 and 3 Radiation: Radiation (Post induction) Monday-Friday, weeks 1-7 Drug: Cisplatin (Post induction) Cisplatin 100 mg/m2 IVPB on radiation day 1, 22 and 42
2: Experimental Induction chemotherapy followed by Radiation therapy plus Cetuximab Induction chemotherapy: Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3. Post-Induction: Radiation - Monday-Friday weeks 1-7 with concurrent Cetuximab (for patients who cannot receive cisplatin) will begin (+/- 3 days) before starting radiation therapy at 400 mg/m2 IVPB. Subsequent doses of cetuximab will be given weekly at 250 mg/m2 IVPB	Drug: Abraxane 100 mg/m2 IVPB, Day 1, 8 and 15 of cycles 1, 2, and 3 Drug: Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1 Drug: Cetuximab 250 mg IVPB, Day 8 and 15 cycle 1, Day 1, 8 and 15 of cycles 2 and 3 Drug: Cisplatin 75 mg/m2 IVPB Day 1, cycles 1, 2 and 3 Drug: 5-FU 750 mg/m2 CIVI Day 1, 2 and 3, cycles 1, 2 and 3 Radiation: Radiation (Post induction) Monday-Friday, weeks 1-7 Drug: Cetuximab (Post-induction) Cetuximab (for patients who cannot receive cisplatin) will begin (+/- 3 days) before starting radiation therapy at 400 mg/m2 IVPB. Subsequent doses of cetuximab will be given weekly at 250 mg/m2 IVPB

Arms

Assigned Interventions

1: Experimental

Induction chemotherapy followed by Radiation therapy plus Cisplatin

Induction chemotherapy:

Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3.

Post-Induction:

Radiation - Monday-Friday weeks 1-7 with concurrent Cisplatin 100 mg/m2 IVPB on radiation day 1, 22, and 42.

Drug: Abraxane

100 mg/m2 IVPB, Day 1, 8 and 15 of cycles 1, 2, and 3

Drug: Cetuximab

400 mg/m2 IVPB, Day 1, cycle 1

Drug: Cetuximab

250 mg IVPB, Day 8 and 15 cycle 1, Day 1, 8 and 15 of cycles 2 and 3

Drug: Cisplatin

75 mg/m2 IVPB Day 1, cycles 1, 2 and 3

Drug: 5-FU

750 mg/m2 CIVI Day 1, 2 and 3, cycles 1, 2 and 3

Radiation: Radiation (Post induction)

Monday-Friday, weeks 1-7

Drug: Cisplatin

(Post induction) Cisplatin 100 mg/m2 IVPB on radiation day 1, 22 and 42

2: Experimental

Induction chemotherapy followed by Radiation therapy plus Cetuximab

Induction chemotherapy:

Abraxane 100 mg/m2 IVPB, Day 1, 8, and 15 of cycles 1, 2, and 3. Cetuximab 400 mg/m2 IVPB, Day 1, cycle 1. Cetuximab 250 mg/m2 IVPB, Day 8 and 15 cycle 1, 2 and 3. Cisplatin 75 mg/m2 IVPB, Day 1, cycles 1, 2, and 3. 5-FU 750 mg/m2 CIVI, Day 1, 2 and 3, cycles 1, 2, and 3.

Post-Induction:

Radiation - Monday-Friday weeks 1-7 with concurrent Cetuximab (for patients who cannot receive cisplatin) will begin (+/- 3 days) before starting radiation therapy at 400 mg/m2 IVPB. Subsequent doses of cetuximab will be given weekly at 250 mg/m2 IVPB

Drug: Abraxane

100 mg/m2 IVPB, Day 1, 8 and 15 of cycles 1, 2, and 3

Drug: Cetuximab

400 mg/m2 IVPB, Day 1, cycle 1

Drug: Cetuximab

250 mg IVPB, Day 8 and 15 cycle 1, Day 1, 8 and 15 of cycles 2 and 3

Drug: Cisplatin

75 mg/m2 IVPB Day 1, cycles 1, 2 and 3

Drug: 5-FU

750 mg/m2 CIVI Day 1, 2 and 3, cycles 1, 2 and 3

Radiation: Radiation (Post induction)

Monday-Friday, weeks 1-7

Drug: Cetuximab

(Post-induction) Cetuximab (for patients who cannot receive cisplatin) will begin (+/- 3 days) before starting radiation therapy at 400 mg/m2 IVPB. Subsequent doses of cetuximab will be given weekly at 250 mg/m2 IVPB

Detailed Description:

Primary objective:

To determine the clinical CR rate (CR-p) at the primary tumor site to an IC regimen of weekly Abraxane and cetuximab with CF (ACCF) given for two cycles (over 6 weeks) in patients with locally advanced non-metastatic HNSCC. The assessment of primary tumor site response will be performed by the treating physician by careful clinical examination using WHO criteria. Radiographic studies will also be performed to assess primary tumor site response but will be used primarily to confirm lack of disease progression that may not be detected based on clinical examination alone.

The secondary objectives include:

Document the clinical PR rate (PR-p) at the primary tumor site with this IC regimen
Document the clinical CR and PR rates at the involved regional nodes (CR-n and PR-n) with this IC regimen
Document the clinical overall CR rate (CR-o) (defined as achievement of a CR at the primary tumor site and at the involved regional nodes) and the clinical overall PR rate (PR-o) with this IC regimen
Document the CR (CR-p, CR-n, and CR-o) and PR (PR-p, PR-n, and PR-o) rates by FDG uptake on PET scan after this IC regimen
Document radiographic CR (CR-p, CR-n, and CR-o) and PR (PR-p, PR-n, and PR-o) rates as assessed by conventional CT scan using RECIST criteria after this IC regimen.
Correlate primary tumor site, nodal and overall tumor response rates based on WHO criteria of assessment with that based on CT scan and FDG-PET/CT.
Document and quantify SPARC expression by IHC in primary tumor tissue obtained at baseline in each patient and attempt to correlate these results with primary tumor site response to ACCF.
Document and grade AE's with this IC regimen with a pre-planned safety analysis after the first ten patients have completed the IC regimen.
Determine the overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) of this patient population.

Eligibility

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

Criteria

Inclusion

Selected Stages 3 and 4a/b 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.
Oropharynx, hypopharynx, larynx, and oral cavity sub-sites only. Patients with nasopharyngeal, sinus and other sub-sites of the head and neck, or unknown primary SCC of the head and neck will NOT be eligible.
Age ≥18 years
Signed informed consent.
ECOG Performance Status (PS) of 0-2 (Appendix 1).
Adequate vital organ function (serum creatinine < 1.8 mg/dl, total bilirubin </= 1.5 mg/dl, ALT and AST </= 2.5 x ULN, alkaline phosphatase </= 2.5 x ULN) and hematopoietic function (ANC >/= 1500/ul, Platelets > 100,000/ul, HGB > 9.0 g/dl).
Patients with reproductive potential must use an effective method of contraception to avoid pregnancy for the duration of the trial and for three months after completing treatment.
If female of childbearing potential, the patient must have a negative pregnancy test.

Exclusion Criteria:

Peripheral neuropathy > Grade 1.
Prior chemotherapy, EGFR targeted therapy or radiation therapy for HNSCC.
History of prior invasive malignancy diagnosed within the last three years other than local stage non-melanoma skin cancer.
Be taking cimetidine or allopurinol. Patients must discontinue taking the medication for one week before receiving treatment with Abraxane.
Be taking cimetidine or allopurinol. Patients must discontinue taking the medication for one week before receiving treatment with Abraxane.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00736944

Contacts

Contact: Douglas Adkins, M.D.

314-747-7402

dadkins@dom.wustl.edu

Locations

United States, Missouri
Washington University	Recruiting
St. Louis, Missouri, United States, 63110
Contact: Douglas Adkins, M.D. 314-747-7402 dadkins@dom.wustl.edu
Sub-Investigator: Brian Nussenbaum, M.D.
Sub-Investigator: Wade Thorstad, M.D.
Sub-Investigator: David Kuperman, M.D.
Sub-Investigator: Barry Siegel, M.D.
Sub-Investigator: Farrokh Dehdashti, M.D.
Sub-Investigator: James Lewis, M.D.
Sub-Investigator: Bruce Haughey, MBBS
Sub-Investigator: Kim Trinkaus, Ph.D.

Sponsors and Collaborators

Washington University School of Medicine

Investigators

Principal Investigator:

Douglas Adkins, M.D.

Washington Univerisity

More Information

Publications:

[No authors listed] Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group. N Engl J Med. 1991 Jun 13;324(24):1685-90.

ten Tije AJ, Verweij J, Loos WJ, Sparreboom A. Pharmacological effects of formulation vehicles : implications for cancer chemotherapy. Clin Pharmacokinet. 2003;42(7):665-85. Review.

Sparreboom A, van Zuylen L, Brouwer E, Loos WJ, de Bruijn P, Gelderblom H, Pillay M, Nooter K, Stoter G, Verweij J. Cremophor EL-mediated alteration of paclitaxel distribution in human blood: clinical pharmacokinetic implications. Cancer Res. 1999 Apr 1;59(7):1454-7.

Winer EP, Berry DA, Woolf S, Duggan D, Kornblith A, Harris LN, Michaelson RA, Kirshner JA, Fleming GF, Perry MC, Graham ML, Sharp SA, Keresztes R, Henderson IC, Hudis C, Muss H, Norton L. Failure of higher-dose paclitaxel to improve outcome in patients with metastatic breast cancer: cancer and leukemia group B trial 9342. J Clin Oncol. 2004 Jun 1;22(11):2061-8.

van Tellingen O, Huizing MT, Panday VR, Schellens JH, Nooijen WJ, Beijnen JH. Cremophor EL causes (pseudo-) non-linear pharmacokinetics of paclitaxel in patients. Br J Cancer. 1999 Sep;81(2):330-5.

Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, Hawkins M, O'Shaughnessy J. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005 Nov 1;23(31):7794-803. Epub 2005 Sep 19.

Kato Y, Nagashima Y, Baba Y, Kawano T, Furukawa M, Kubota A, Yanoma S, Imagawa-Ishiguro Y, Satake K, Taguchi T, Hata R, Mochimatsu I, Aoki I, Kameda Y, Inayama Y, Tsukuda M. Expression of SPARC in tongue carcinoma of stage II is associated with poor prognosis: an immunohistochemical study of 86 cases. Int J Mol Med. 2005 Aug;16(2):263-8.

Responsible Party:	Washington University ( Douglas Adkins, M.D. )
Study ID Numbers:	08-0911
Study First Received:	August 13, 2008
Last Updated:	October 27, 2008
ClinicalTrials.gov Identifier:	NCT00736944
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Squamous cell carcinoma
Cetuximab
Carcinoma
Epidermoid carcinoma
Cisplatin
Paclitaxel
Head and Neck Neoplasms

Fluorouracil
Carcinoma, squamous cell
Neoplasms, Squamous Cell
Carcinoma, Squamous Cell
Carcinoma, squamous cell of head and neck
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Radiation-Sensitizing Agents
Antineoplastic Agents
Therapeutic Uses

Mitosis Modulators
Tubulin Modulators
Physiological Effects of Drugs
Antimitotic Agents
Antineoplastic Agents, Phytogenic
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009