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

NCT ID: NCT00736944

Last Updated: 2020-09-09

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-12-19

Study Completion Date

2020-07-06

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Squamous Cell Carcinoma of the Head and Neck

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

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.

Group Type EXPERIMENTAL

Abraxane

Intervention Type DRUG

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

Cetuximab

Intervention Type DRUG

400 mg/m2 IVPB, Day 1, cycle 1

Cetuximab

Intervention Type DRUG

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

Cisplatin

Intervention Type DRUG

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

5-FU

Intervention Type DRUG

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

Radiation (Post induction)

Intervention Type RADIATION

Monday-Friday, weeks 1-7

Cisplatin

Intervention Type DRUG

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

2

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

Group Type EXPERIMENTAL

Abraxane

Intervention Type DRUG

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

Cetuximab

Intervention Type DRUG

400 mg/m2 IVPB, Day 1, cycle 1

Cetuximab

Intervention Type DRUG

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

Cisplatin

Intervention Type DRUG

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

5-FU

Intervention Type DRUG

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

Radiation (Post induction)

Intervention Type RADIATION

Monday-Friday, weeks 1-7

Cetuximab

Intervention Type DRUG

(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

Interventions

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Abraxane

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

Intervention Type DRUG

Cetuximab

400 mg/m2 IVPB, Day 1, cycle 1

Intervention Type DRUG

Cetuximab

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

Intervention Type DRUG

Cisplatin

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

Intervention Type DRUG

5-FU

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

Intervention Type DRUG

Radiation (Post induction)

Monday-Friday, weeks 1-7

Intervention Type RADIATION

Cisplatin

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

Intervention Type 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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene Corporation

INDUSTRY

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Douglas Adkins, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington Univerisity

Locations

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Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Countries

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United States

References

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Department of Veterans Affairs Laryngeal Cancer Study Group; Wolf GT, Fisher SG, Hong WK, Hillman R, Spaulding M, Laramore GE, Endicott JW, McClatchey K, Henderson WG. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med. 1991 Jun 13;324(24):1685-90. doi: 10.1056/NEJM199106133242402.

Reference Type BACKGROUND
PMID: 2034244 (View on PubMed)

JCO 12:1592, 1194

Reference Type BACKGROUND

Hitt R, Lopez-Pousa A, Martinez-Trufero J, Escrig V, Carles J, Rizo A, Isla D, Vega ME, Marti JL, Lobo F, Pastor P, Valenti V, Belon J, Sanchez MA, Chaib C, Pallares C, Anton A, Cervantes A, Paz-Ares L, Cortes-Funes H. Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally advanced head and neck cancer. J Clin Oncol. 2005 Dec 1;23(34):8636-45. doi: 10.1200/JCO.2004.00.1990. Epub 2005 Nov 7.

Reference Type BACKGROUND
PMID: 16275937 (View on PubMed)

Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA; Eastern Cooperative Oncology Group. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol. 2005 Dec 1;23(34):8646-54. doi: 10.1200/JCO.2005.02.4646.

Reference Type BACKGROUND
PMID: 16314626 (View on PubMed)

Kuperman, et al ASCO 2007

Reference Type BACKGROUND

Kies, et al ASCO 2006

Reference Type BACKGROUND

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. doi: 10.2165/00003088-200342070-00005.

Reference Type BACKGROUND
PMID: 12844327 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10197613 (View on PubMed)

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. doi: 10.1200/JCO.2004.08.048.

Reference Type BACKGROUND
PMID: 15169793 (View on PubMed)

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. doi: 10.1038/sj.bjc.6690696.

Reference Type BACKGROUND
PMID: 10496361 (View on PubMed)

Desai N, et al SABCS Dec, 2003

Reference Type BACKGROUND

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. doi: 10.1200/JCO.2005.04.937. Epub 2005 Sep 19.

Reference Type BACKGROUND
PMID: 16172456 (View on PubMed)

Gradishar,et al SABCS 2006

Reference Type BACKGROUND

SABCS 2006

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 16012759 (View on PubMed)

Mendez E, et al Cancer 95:1482-1494, 2005

Reference Type BACKGROUND

Desai N, et al SABCS Dec, 2004

Reference Type BACKGROUND

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.

Reference Type DERIVED
PMID: 28797458 (View on PubMed)

Related Links

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http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

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08-0911 / 201105501

Identifier Type: -

Identifier Source: org_study_id

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