Induction Chemotherapy Followed by Cetuximab and Radiation Therapy for Head and Neck Cancer

NCT01467115 | Completed Phase 2 DMC

• 1 other identifier: 19834
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

More than 50% of Head and Neck cancers are locally advanced at presentation. Although surgery, in combination with other modalities like radiation therapy can achieve 40-50% five year survival rates, resection in the head and neck region can leave patients with poor functional and cosmetic outcomes. Due to these concerns about quality of life after surgery, there has been a lot of interest in non surgical alternatives of treatment. Various combinations of radiation, chemotherapy and biologics has showed promising results. However, questions still remain about the ideal combination treatment regimen. Based on assimilation of data from multiple sources, our study tries to identify the role of a potentially highly effective multi-modality regimen based on induction chemotherapy (Cisplatin, Docetaxel and 5 Fluorouracil) followed by combination of a biologic agent, Cetuximab, and radiation therapy.

Conditions

Head and Neck Cancer

Keywords

loco regionally advanced; head and neck cancer; chemotherapy; radiation

Outcome Measures

Primary Outcomes (1)

• Organ Sparing Survival

  to determine whether the intervention will prolong survival without needing salvage surgery (organ sparing survival)

  3 years

Secondary Outcomes (1)

• Overall Survival

  3 years

Study Arms (1)

Treatment

EXPERIMENTAL

Treatment with induction chemotherapy followed by radiation and cetuximab.

Radiation: Radiotherapy; Drug: Leucovorin; Biological: Cetuximab; Drug: Filgrastim; Drug: Erythropoetin; Drug: Cisplatin; Drug: Fluorouracil; Drug: Docetaxel

Interventions

Radiotherapy RADIATION

3D conformal radiation therapy or Intensity-Modulated Radiation Therapy (IMRT) with or without Image Guided Radiation Therapy (IGRT) will be used for all patients. Radiotherapy will be delivered in 1.8 to 2.25 Gy fractions daily, five days per week excluding holidays, for a total of 66-72 Gy delivered to the Gross Tumor Volume (GTV, defined below) plus appropriate margin and 44-59.4 Gy to at-risk lymph nodes as determined by primary tumor characteristics. Alternative fractionation and dosing schema may be used as deemed appropriate for an individual case. For IMRT, the minimum Planning Target Volume (PTV) dose should be 90% of the prescription dose and a minimum of 95% of the PTV should receive the prescribed dose.

Also known as: 3D conformal radiation therapy, Intensity-Modulated Radiation Therapy (IMRT)

Treatment

Leucovorin DRUG

5FU is given after, or at the midpoint, of the leucovorin infusion. Leucovorin is usually administered by I.V. bolus injection or short (10-120 minutes) I.V. infusion but oral formulation may be substituted should supply warrant.

Also known as: Folinic acid, Leucovorin Ca.

Treatment

Cetuximab BIOLOGICAL

Cetuximab will be given for the duration of radiotherapy. A loading dose of intravenous cetuximab at 400mg per square meter body-surface area will be given over two hours up to seven days prior to initiation of radiation treatments or on the day of the first treatment (drug information detailed below). Thereafter, cetuximab will be given weekly over 60 minutes at a dose of 250 mg per meter squared. Intravenous diphenhydramine (50 mg) will be given as premedication.

Also known as: Erbitux

Treatment

Filgrastim DRUG

Neupogen®: 300 mcg/mL (1 mL, 1.6 mL). May be administered undiluted by SubQ injection. May also be administered by I.V. bolus over 15-30 minutes in D5W, or by continuous SubQ or I.V. infusion. Do not administer earlier than 24 hours after or in the 24 hours prior to cytotoxic chemotherapy.

Also known as: Neupogen

Treatment

Erythropoetin DRUG

Subcutaneous or intravenous

Also known as: Epogen®; Procrit®

Treatment

Cisplatin DRUG

One cycle of induction chemotherapy will be comprised of docetaxel on day 1 and cisplatin and 5-fluorouracil given days 1, 8, and 15. Intravenous docetaxel will be administered over one hour at a dose of 75 mg per square meter of body-surface area, followed by intravenous cisplatin at 35 mg per square meter, administered during a period of 0.5 to 3 hours weekly. After completion of the cisplatin infusion, intravenous fluorouracil will be given as a bolus at 1000 mg per square meter, followed by leucovorin at the dose of 350mg/m2. There will be total 4 cycles of chemotherapy of which 2 cycles will be prior to radiation therapy and 2 cycles will be post-radiation.

Also known as: Platinol AQ

Treatment

Fluorouracil DRUG

One cycle of induction chemotherapy will be comprised of docetaxel on day 1 and cisplatin and 5-fluorouracil given days 1, 8, and 15. Intravenous docetaxel will be administered over one hour at a dose of 75 mg per square meter of body-surface area, followed by intravenous cisplatin at 35 mg per square meter, administered during a period of 0.5 to 3 hours weekly. After completion of the cisplatin infusion, intravenous fluorouracil will be given as a bolus at 1000 mg per square meter, followed by leucovorin at the dose of 350mg/m2. There will be total 4 cycles of chemotherapy of which 2 cycles will be prior to radiation therapy and 2 cycles will be post-radiation.

Treatment

Docetaxel DRUG

One cycle of induction chemotherapy will be comprised of docetaxel on day 1 and cisplatin and 5-fluorouracil given days 1, 8, and 15. Intravenous docetaxel will be administered over one hour at a dose of 75 mg per square meter of body-surface area, followed by intravenous cisplatin at 35 mg per square meter, administered during a period of 0.5 to 3 hours weekly. After completion of the cisplatin infusion, intravenous fluorouracil will be given as a bolus at 1000 mg per square meter, followed by leucovorin at the dose of 350mg/m2. There will be total 4 cycles of chemotherapy of which 2 cycles will be prior to radiation therapy and 2 cycles will be post-radiation.

Also known as: Taxotere

Treatment

Eligibility Criteria

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

You may qualify if:

• Biopsy and/or fine needle aspirate of the tumor is required prior to registration. Pathologically confirmed primary squamous cell cancer of the oral cavity, oropharynx, hypopharynx, larynx, or unknown primary confined to the head and neck; histological variants such as spindle cell carcinoma, poorly differentiated keratin-positive carcinoma, and lymphoepithelioma are included. Patients with nasopharyngeal and salivary gland tumors are ineligible.
• Measureable disease representing stage III or stage IVa or IVb cancer by AJCC staging is required (See Appendix II)
• Measureable disease representing stage II cancer qualifies if the patient refuses surgery or is unable to undergo surgery as curative treatment
• Patient must not have had previous irradiation or surgery other than biopsy of the head and neck region
• A CT of the chest and CT or MRI of the tumor site is required within four weeks prior to registration
• Appropriate staging evaluation is required within four weeks prior to registration, including the following:
• history and physical examination with special attention to functional status measures, carotid arteries, neck and clavicular lymph nodes
• chest CT with evaluation of any nodules ≥ 1cm with biopsy or PET/CT (patients with lesions \< 1cm, negative on PET scan, or that cannot be safely biopsied remain eligible).
• ECOG performance status 0-2 (See Appendix III)
• Age ≥ 18 years
• Complete blood count evaluation within two weeks of treatment demonstrating absolute neutrophil count ≥ 1500/mm3, platelets ≥100,000 cells/mm3, and hemoglobin ≥ 8g/dL
• Liver function tests within two weeks of treatment demonstrating total bilirubin ≤1.5 mg/dL, AST and ALT \< 2x upper limit of normal, and alkaline phosphatase \< 2x upper limits of normal; an abdominal CT scan is required if any of the above criteria are not met
• Adequate renal function measured within two weeks of treatment, defined as a creatinine clearance ≥ 50 ml/min determined by a 24 hour urine creatinine or the Cockcroft-Gault equation, where creatinine clearance (ml/min) is equal to:
• \[(140 - age) x (wt in kg)\] x 0.85 for females \[(sCR) x (72)\]
• Corrected serum calcium \<11 mg/dL within two weeks prior to treatment.

You may not qualify if:

• Evidence of metastatic disease
• Prior head and neck cancer.
• History of invasive cancer of any primary sight not considered cured.
• Previous radiation to the head and neck
• Nasopharyngeal or salivary gland cancer
• Severe, active comorbidity, defined as:
• New York Heart Association Class III or IV heart failure (Appendix IV)
• Unstable angina
• Acute bacterial or fungal infection requiring antibiotic treatment
• Chronic obstructive pulmonary disease requiring long term oral steroids or hospitalization for exacerbation within three months of study registration
• Liver dysfunction resulting in clinical jaundice or coagulation defects
• Acquired Immune Deficiency Syndrome defined as CD4 count \<200 or opportunistic AIDS defining infection requiring active antibiotic treatment
• Pregnancy, lactation, or refusal of patient to take appropriate medical or behavioral measures to prevent pregnancy
• Pre-existing peripheral neuropathy \> grade 2
• Hypersensitivity reaction to any drug listed in the protocol

Sponsors & Collaborators

• Drexel University College of Medicine: lead

Study Sites (1)

Hahnemann University Hospital

Philadelphia, Pennsylvania, 19102, United States

Location

Related Publications (8)

• Haddad RI, Shin DM. Recent advances in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1143-54. doi: 10.1056/NEJMra0707975. No abstract available.

  PMID: 18784104 BACKGROUND

• Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96. doi: 10.3322/CA.2007.0010. Epub 2008 Feb 20.

  PMID: 18287387 BACKGROUND

• Deshmane VH, Parikh HK, Pinni S, Parikh DM, Rao RS. Laryngectomy: a quality of life assessment. Indian J Cancer. 1995 Sep;32(3):121-30.

  PMID: 8772812 BACKGROUND

• De Boer MF, McCormick LK, Pruyn JF, Ryckman RM, van den Borne BW. Physical and psychosocial correlates of head and neck cancer: a review of the literature. Otolaryngol Head Neck Surg. 1999 Mar;120(3):427-36. doi: 10.1016/S0194-5998(99)70287-1.

  PMID: 10064650 BACKGROUND

• 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

• Paccagnella A, Orlando A, Marchiori C, Zorat PL, Cavaniglia G, Sileni VC, Jirillo A, Tomio L, Fila G, Fede A, et al. Phase III trial of initial chemotherapy in stage III or IV head and neck cancers: a study by the Gruppo di Studio sui Tumori della Testa e del Collo. J Natl Cancer Inst. 1994 Feb 16;86(4):265-72. doi: 10.1093/jnci/86.4.265.

  PMID: 8158680 BACKGROUND

• Zorat PL, Paccagnella A, Cavaniglia G, Loreggian L, Gava A, Mione CA, Boldrin F, Marchiori C, Lunghi F, Fede A, Bordin A, Da Mosto MC, Sileni VC, Orlando A, Jirillo A, Tomio L, Pappagallo GL, Ghi MG. Randomized phase III trial of neoadjuvant chemotherapy in head and neck cancer: 10-year follow-up. J Natl Cancer Inst. 2004 Nov 17;96(22):1714-7. doi: 10.1093/jnci/djh306.

  PMID: 15547184 BACKGROUND

• Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006 Feb 9;354(6):567-78. doi: 10.1056/NEJMoa053422.

  PMID: 16467544 BACKGROUND

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Radiotherapy; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Leucovorin; Cetuximab; Filgrastim; Erythropoietin; Epoetin Alfa; Cisplatin; Fluorouracil; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Therapeutics; Radiotherapy, Computer-Assisted; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Rene R Rubin, MD

  Drexel University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 4, 2011
• First Posted: November 8, 2011
• Study Start: March 1, 2010
• Primary Completion: June 1, 2014
• Study Completion: October 7, 2014
• Last Updated: May 9, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)