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

NCT00736944 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 08-0911 / 201105501
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Outcome Measures

Primary Outcomes (1)

• Clinical Complete Response Rate at the Primary Tumor

  Clinical exam included laryngoscopy in office or operating room. Complete response rate includes complete response (CR) which is defined as 100% decrease in tumor size and it also includes near complete response (near CR) defined as 95-99% decrease in tumor size.

  post-2 cycles of induction (approximately 42 days from start of treatment)

Secondary Outcomes (19)

• Clinical Partial Response Rate at the Primary Tumor

  post-2 cycles of induction therapy (approximately 42 days from start of treatment)

• Clinical Complete and Partial Response Rates to the Involved Regional Nodes

  post-2 cycles of induction therapy (approximately 42 days from start of treatment)

• Clinical Overall Complete and Partial Response Rates

  post-2 cycles of induction therapy (approximately 42 days)

• Complete and Partial Response Rates of Primary Tumor by FDG Uptake on PET Scan

  post-2 cycles of induction therapy (approximately 42 days from start of treatment)

• Complete and Partial Response Rates of Involved Lymph Nodes by FDG Uptake on PET Scan

  post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Other Outcomes (1)

• Overall Complete and Partial Response Rates by FDG Uptake on PET Scan

  post-2 cycles of induction therapy (approximately 42 days from start of treatment)

Study Arms (2)

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; Drug: Cetuximab; Drug: Cisplatin; Drug: 5-FU; Radiation: Radiation (Post induction)

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; Drug: Cetuximab; Drug: Cisplatin; Drug: 5-FU; Radiation: Radiation (Post induction)

Interventions

Abraxane DRUG

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

1; 2

Cetuximab DRUG

400 mg/m2 IVPB, Day 1, cycle 1

1; 2

Cisplatin DRUG

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

1; 2

5-FU DRUG

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

1; 2

Radiation (Post induction) RADIATION

Monday-Friday, weeks 1-7

1; 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Celgene Corporation: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (18)

• 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.

  PMID: 2034244 BACKGROUND

• JCO 12:1592, 1194

  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.

  PMID: 16275937 BACKGROUND

• 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.

  PMID: 16314626 BACKGROUND

• Kuperman, et al ASCO 2007

  BACKGROUND

• Kies, et al ASCO 2006

  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.

  PMID: 12844327 BACKGROUND

• 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.

  PMID: 10197613 BACKGROUND

• 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.

  PMID: 15169793 BACKGROUND

• 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.

  PMID: 10496361 BACKGROUND

• Desai N, et al SABCS Dec, 2003

  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.

  PMID: 16172456 BACKGROUND

• Gradishar,et al SABCS 2006

  BACKGROUND

• SABCS 2006

  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.

  PMID: 16012759 BACKGROUND

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

  BACKGROUND

• Desai N, et al SABCS Dec, 2004

  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.

  PMID: 28797458 DERIVED

Related Links

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

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Albumin-Bound Paclitaxel; Cetuximab; Cisplatin; Fluorouracil; Radiation

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Physical Phenomena

Results Point of Contact

• Title: Dr. Douglas R. Adkins
• Organization: Washington University School of Medicine

dadkins@dom.wustl.edu

314-362-5654

Study Officials

• Douglas Adkins, M.D.

  Washington Univerisity

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2008
• First Posted: August 18, 2008
• Study Start: December 19, 2008
• Primary Completion: August 31, 2010
• Study Completion: July 6, 2020
• Last Updated: September 9, 2020
• Results First Posted: January 7, 2014

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)