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Carcinoma, Squamous Cell of Head and NeckPhase 2NCT01588431

Bevacizumab/Ph 2 for Locally Advanced Head and Neck Cancer

A Phase 2 study testing Docetaxel, Cisplatin, Cetuximab and Bevacizumab (TPE-A) Followed by Concurrent Radiation, Cisplatin, Cetuximab and Bevacizumab (XPE-A), surgery in people with Carcinoma, Squamous Cell of Head and Neck, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Docetaxel, Cisplatin, Cetuximab and Bevacizumab (TPE-A) Followed by Concurrent Radiation, Cisplatin, Cetuximab and Bevacizumab (XPE-A), surgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
Dec 2011to 4 Oct 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • NOTE: UPC ratio of spot urine is an estimation of the 24-urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1gm. UPC ratio is calculated using one of the following formula:
  • [urine protein]/[urine creatinine] - if both protein and creatinine are reported in mg/DI
  • [(urine protein) × 0.088]/[urine creatinine] - if urine creatinine is reported in mmol/L
  • Patients with a prior history of squamous cell or basal carcinoma of the skin or in situ cervical cancer must have been curatively treated. Patients with a history of other prior malignancy must have been treated with curative intent and must have remained disease-free for 3 years post diagnosis.
  • Patients may not be receiving any other investigational agents.

Who cannot join

  • 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.
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  • 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)
  • Patients should not be on therapeutic anticoagulation therapy (prophylactic use of warfarin 1mg per day is allowed) and INR should be <1.5 at registration
  • The use of anti-platelet agents (e.g. dipyridamole (Persatine), ticlopidine (Ticlid), clopidogrel (Plavix)) is allowed only if patient is not receiving aspirin or NSAID's known to inhibit platelet function.
  • Major surgical procedure (including neck dissection), open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
  • History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
  • Serious, non-healing wound, active ulcer, or untreated bone fracture
  • Pregnant or breast-feeding women will be excluded.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Cancer Therapy and Research Center at UTHSCSA

    San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: A Phase II Study of Induction Docetaxel, Cisplatin, Cetuximab and Bevacizumab (TPE-A) Followed by Concurrent Radiation, Cisplatin, Cetuximab and Bevacizumab (XPE-A) in Patients With Locally Advanced Head and Neck Cancer (CTRC# 11-36)

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.

Read the detailed description

Locally advanced squamous cell carcinoma of the head and neck (SCCHN) is treated with various combinations of radiation and chemotherapy. Docetaxel and cisplatin have been combined in Phase II trials in recurrent or metastatic head and neck cancer with very encouraging results. Induction therapy with docetaxel/cisplatin followed by chemoradiotherapy was investigated in a randomized Phase II study in nasopharyngeal cancer and showed superior PFS and OS in comparison with chemoradiation alone. Cetuximab is a chimerized EGFR monoclonal antibody that has produced positive results in Phase III trials in combination with either radiation for locally advanced disease or chemotherapy for metastatic disease. Upregulation of vascular endothelial growth factor (VEGF) has been associated with cetuximab resistance. Bevacizumab, an anti-VEGF antibody is currently being investigated in SCCHN with promising results. The investigators have previously shown that cisplatin, docetaxel and cetuximab (TPE) followed by radiotherapy, cisplatin and cetuximab (XPE) is feasible and highly efficacious in locally advanced SCCHN (Argiris, A. et al.JCO 2011). In this Phase II study the investigators evaluate the addition of bevacizumab to induction therapy with TPE (TPE-A) and to subsequent XPE (XPE-A).

Specific aims:

To evaluate the rate of complete responses with induction therapy (primary endpoint) and progression-free survival, overall survival and objective response rates. 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.

Subject population:

The investigators will enroll patients with previously untreated locally advanced SCCHN (see detailed eligibility criteria).

Treatment plan:

Induction therapy consists of 3 cycles of bevacizumab 15mg/kg on day 1, docetaxel 75mg/m2 on day 1, loading dose of cetuximab 400mg/m2 on cycle 1, day 1, then 250 mg/m2 on all subsequent administrations (Day 8 and 15 of cycle 1 and days 1,8,15 of cycles 2 and 3), 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.

Statistical design and sample size:

Phase II, two-stage study with complete response rate after induction therapy as the primary endpoint. The sample size is 33 patients.

Being tested
Docetaxel, Cisplatin, Cetuximab and Bevacizumab (TPE-A) Followed by Concurrent Radiation, Cisplatin, Cetuximab and Bevacizumab (XPE-A), surgery
Keywords
Locally advanced head and neck cancer, Squamous cell carcinoma of the head and neck
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    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.

Study groups in NCT01588431
Study groupRoleWhat they receive
(TPE-A) Followed by Concurrent RT(XPE-A), surgeryExperimentalDocetaxel, Cisplatin, Cetuximab and Bevacizumab (TPE-A) Followed by Concurrent Radiation, Cisplatin, Cetuximab and Bevacizumab (XPE-A), surgery
Receives: Drug: Docetaxel, Cisplatin, Cetuximab and Bevacizumab (TPE-A) Followed by Concurrent Radiation, Cisplatin, Cetuximab and Bevacizumab (XPE-A), surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 1year up to 10 years

Secondary outcomes (1)

  1. Level of Angiogenesis Biomarkers

    Investigate a panel of Epidermal Growth Factor Receptor (EGFR) and angiogenesis biomarkers in pre- and post- treatment tumor biopsies and evaluate the associated treatment toxicities and the quality of life. After 8 weeks of chemo + radiation; 1 year up to 10 years.

    Measured: 8 weeks up to 10 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 May 2012 (estimated)
  2. Study startDec 2011
  3. Primary completion4 Oct 2022
  4. Study completion4 Oct 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01588431
Sponsor's protocol ID
CTRC 11-36
Other IDs
HSC20120002H
Status last verified
Jan 2024
First submitted
29 Feb 2012
Last updated
14 Feb 2024
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Docetaxel, Cisplatin, Cetuximab and Bevacizumab (TPE-A) Followed by Concurrent Radiation, Cisplatin, Cetuximab and Bevacizumab (XPE-A), surgery in people with Carcinoma, Squamous Cell of Head and Neck, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Response (time frame: 1year up to 10 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01588431.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2024.

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