Bevacizumab/Ph 2 for Locally Advanced Head and Neck Cancer

NCT01588431 | Completed Phase 2 Results DMC

• 2 other identifiers: CTRC 11-36HSC20120002H
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Locally advanced squamous cell carcinoma of the head and neck (SCCHN) is treated with various combinations of radiation and chemotherapy. This study aims to evaluate the rate of complete responses with induction therapy (primary endpoint) and progression-free survival, overall survival and objective response rates of docetaxel, cisplatin, cetuximab, and bevacizumab (TPE-A) followed by radiation therapy, cisplatin, cetuximab, and bevacizumab (XPE-A). Also, the investigators plan to investigate a panel of EGFR and angiogenesis biomarkers in pre-and post- treatment tumor biopsies. Finally, the investigators will evaluate the associated treatment toxicities and the quality of life.

Conditions

Carcinoma, Squamous Cell of Head and Neck

Keywords

Locally advanced head and neck cancer; Squamous cell carcinoma of the head and neck

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Response

  Evaluate the rate of complete responses with induction therapy - Change in baseline regarding treatment/tumor response after 3 cycles of chemotherapy (3months); After 8 weeks of chemo + radiation; 1 year up to 10 years. This outcome will be measured with regards to number of participants via RECIST criteria.

  1year up to 10 years

Secondary Outcomes (1)

• Level of Angiogenesis Biomarkers

  8 weeks up to 10 years

Study Arms (1)

(TPE-A) Followed by Concurrent RT(XPE-A), surgery

EXPERIMENTAL

Docetaxel, Cisplatin, Cetuximab and Bevacizumab (TPE-A) Followed by Concurrent Radiation, Cisplatin, Cetuximab and Bevacizumab (XPE-A), surgery

Drug: Docetaxel, Cisplatin, Cetuximab and Bevacizumab (TPE-A) Followed by Concurrent Radiation, Cisplatin, Cetuximab and Bevacizumab (XPE-A), surgery

Interventions

Docetaxel, Cisplatin, Cetuximab and Bevacizumab (TPE-A) Followed by Concurrent Radiation, Cisplatin, Cetuximab and Bevacizumab (XPE-A), surgery DRUG

Induction therapy consists of 3 cycles of bevacizumab 15mg/kg on day 1, cetuximab weekly days 1,8,15 (loading dose of cetuximab 400mg/m2 on cycle 1, day 1, then 250 mg/m2 on all subsequent administrations), cisplatin 75mg/m2 on day 1, docetaxel 75mg/m2 on day 1, repeated every 21 days. After 3 cycles of induction therapy, patients will receive standard radiation 70-74 Gy/ 200 cGy/ daily, 5 days/ week with concurrent weekly cisplatin 30mg/m2, cetuximab 250mg/m2 and bevacizumab 15mg/kg every 3 weeks x 3. There is optional surgery for non-responders in the primary (stable disease) after TPE-A.

(TPE-A) Followed by Concurrent RT(XPE-A), surgery

Eligibility Criteria

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

You may qualify if:

• Patients with AJCC 7th edition stage III-IVB head and neck cancer, all sites, including unknown primary tumors.
• Prior to entry in the study the resectability and alternative treatment options for each patient will be determined by a team composed of an Ear, Nose, and Throat Surgeon, a Radiation Oncologist and a Medical Oncologist. Stage determination, optimal local treatment, and its timing according to this protocol will be determined at this evaluation. The unequivocal demonstration of distant metastasis (M1) confers ineligibility.
• Histologically or cytologically confirmed diagnosis of squamous cell or poorly differentiated carcinomas, or WHO types I-III of the nasopharynx.
• Unidimensionally measurable disease is required (RECIST 1.1).
• No prior chemotherapy, biologic/molecular targeted therapy (including any prior therapy which specifically and directly targets the EGFR pathway), or radiotherapy for head and neck cancer.
• Prior surgical therapy will consist only of incisional or excisional biopsy, and organ sparing procedures such as debulking of airway compromising tumors or neck dissection in a patient with an existing primary tumor. Any non-biopsy procedure must have taken place \> 4 weeks but \< 3 months of initiating protocol treatment.
• ECOG performance status 0-1.
• Age 18 years or older.
• Informed consent must be obtained from all patients prior to beginning therapy. Patients should have the ability to understand and the willingness to sign a written informed consent document.
• All patients should have their tumor tissue tested for HPV (in situ hybridization and/or p16 staining by immunohistochemistry), and results must be known prior to study entry, and will consent to have available archival tumor samples, unstained slides or blocks from previous diagnostic or therapeutic procedures submitted for correlative studies, including assessment of target molecules EGFR, VEGF and related biomarkers. Also, patients must agree to submit blood samples for correlative studies at least at baseline.
• Absolute neutrophil count at or above 1500/µl, Platelet count at or above 100,000/µl
• Creatinine clearance 60 ml/min or higher calculated using the Cockcroft-Gault formula:
• Calculated Creatinine Clearance = (140-age) X actual body wt (kg)/ 72 X serum creatinine Multiply this number by 0.85 if the patient is female
• Total bilirubin within normal limits and AST/ALT less than 3 times the upper limit of normal.
• Urine dipstick must be \< 0-1+ within 2 weeks (14 days) of randomization. If urine dipstick result is \> 1+, a calculation of Urine Protein Creatinine (UPC) ratio is required. Patients must have a UPC ratio \< 1.0 to participate in the study.

You may not qualify if:

• History of severe allergic reactions attributed to docetaxel or compounds of similar chemical or biologic composition to docetaxel, or other drugs formulated with polysorbate 80.
• Prior severe infusion reaction to a monoclonal antibody or known hypersensitivity to any component of bevacizumab
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
• All patients will have a baseline EKG. If abnormalities consistent with active coronary artery disease are detected, the patient will be referred to a cardiologist for appropriate evaluation and management prior to treatment on study
• No patients with significant baseline sensory or motor neurologic deficits (\> grade I neuropathy) will be treated on this study.
• Because patients with immune deficiency are at increased risk of lethal Infections when treated with marrow-suppressive therapy, HIV-positive patients are excluded from the study. Appropriate studies will be undertaken in patients with HIV and those receiving combination anti- retroviral therapies when indicated.
• Patients with HPV positive tumors (P16+ by immunohistochemistry and/or HPV+ by in situ hybridization) AND smoking history =\<10 pack-years
• Inadequately controlled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \>100 mmHg)
• Prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• History of myocardial infarction or unstable angina within 12 months prior to Day 1
• No history of stroke or transient ischemic attack within 6 months prior to Day 1
• Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
• History of hemoptysis (\> or = to 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (1)

Cancer Therapy and Research Center at UTHSCSA

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms

Interventions

Docetaxel; Cisplatin; Cetuximab; Bevacizumab; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Anand Karnad, MD
• Organization: UT Health San Antonio

karnad@uthscsa.edu

210-450-1267

Study Officials

• Ahmad Wehbe, MD

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: February 29, 2012
• First Posted: May 1, 2012
• Study Start: December 1, 2011
• Primary Completion: October 4, 2022
• Study Completion: October 4, 2022
• Last Updated: February 14, 2024
• Results First Posted: February 14, 2024

Record last verified: 2024-01

Locations

US (1)