Head and Neck NeoplasmsPhase 2NCT01262859
Pilot Study for Locally Advanced Head and Neck Cancer
A Phase 2 study testing bevacizumab in people with Head and Neck Neoplasms, run by University of Pittsburgh at 1 site in United States.
Trial summary
Induction chemotherapy is gaining momentum in the management of locally advanced squamous cell carcinoma of the head and neck (SCCHN). The combination of docetaxel, cisplatin, and 5-FU (TPF) was superior compared with PF in a Phase III clinical trials73,74. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Neoplasms
- What is being tested?
- bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2010to Jul 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 6th 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 of at least 18 years.
- 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 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 equal to or greater than 1500/µl, Platelet count equal to or greater than 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 to protein to creatinine (UPC) ratio should be <1.0 at screening
- 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
- 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 (see Appendix F)
- 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 (equal to or greater than 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, 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
Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: Pilot 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
Induction chemotherapy is gaining momentum in the management of locally advanced squamous cell carcinoma of the head and neck (SCCHN). The combination of docetaxel, cisplatin, and 5-FU (TPF) was superior compared with PF in a Phase III clinical trials73,74. We have completed a Phase II clinical trial that showed that docetaxel, cisplatin, and cetuximab (TPE) is highly active and well tolerated as induction chemotherapy in SCCHN (Argiris et al. ASCO 2008; A6002). Preliminary survival results are very encouraging. 39 patients were enrolled and with median follow up 26 months the 2-year PFS was 70% and the 2-year OS 84%.The combination of chemotherapy plus cetuximab is already a standard treatment in recurrent or metastatic SCCHN47. Therefore, TPE can be used as the platform for the addition of novel agents.
EGFR and VEGF are among the most important and validated molecular targets in cancer therapy. The incorporation of novel targeted therapies to chemotherapy and radiotherapy is of particular interest in head and neck cancer, and may improve efficacy without significantly increasing toxicity. A Phase III trial of carboplatin/paclitaxel/bevacizumab with or without cetuximab in advanced NSCLC has been proposed by SWOG. Bevacizumab is currently being investigated in SCCHN with promising results. A Phase II study investigating the combination of pemetrexed and bevacizumab (UPCI 05-002) as well as a Phase II trial of cetuximab and bevacizumab (UPCI 05-087) in recurrent or metastatic SCCHN are ongoing at the University of Pittsburgh with encouraging results (ASCO 2008 and ASCO 2009). In this study, 32 have been already enrolled. There was only 1 patient with grade 3 hemorrhage. The objective response rate is 20%, the median PFS 2.8 months and the median OS 8.1 months.
In order to further improve the efficacy of TPE and the rate of complete responses we propose to add bevacizumab to the TPE followed by XPE regimen we developed at the University of Pittsburgh. Due to non-overlapping toxicities and based on our prior experience we anticipate that the regimen will be well tolerated. Moreover, we plan to obtain tumor biopsies and blood samples in the first cycle and evaluate the modulation of biomarkers post combination therapy. Data from induction with TPE (presented at ASCO 2009) indicate the potential significance of cytokine levels in patient outcome. Also, we will evaluate the feasibility of subsequent concurrent radiation, cisplatin, cetuximab and bevacizumab. Patients with stable disease in the primary could be considered candidates to surgical resection at the discretion of their physician, if the tumor is resectable.
- Conditions
- Head and Neck Neoplasms
- Being tested
- bevacizumab
- Medical subject headings
- Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumabDrug
Also called Avastin
Bevacizumab, 15 mg/kg IV over 30 minutes (if this infusion rate was well tolerated), every 3 weeks until completion of radiation The initial dose will be delivered over 90+/-15 minutes. If the first infusion is tolerated without infusion associated adverse events (fever and/or chills), the second infusion may be delivered over 60+/-10 minutes. If the 60 minute infusion is well tolerated, all subsequent infusions may be delivered over 30+/-10 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Study Intervention | Experimental | 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. Receives: Drug: bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate
To evaluate the rate of complete responses with induction with cisplatin, docetaxel, cetuximab and bevacizumab (TPE-A) in patients with locally advanced head and neck cancer.
Measured: 10 years
Secondary outcomes (4)
Serum Correlatives
To evaluate serum cytokines and to correlate with complete response rate post induction therapy.
Measured: 10 years
Biomarkers
To collect tumor tissue from pretreatment and post-treament (optional) biopsies for biomarker studies on tumor tissue. We plan to investigate a panel of EGFR and angiogenesis biomarkers on Tissue Microarrays (TMAs).
Measured: 10 years
Toxicity
To evaluate the toxicities associated with induction TPE-A and subsequent concurrent radiation, cispaltin, cetuximab and bevacizumab (XPE-A).
Measured: 10 years
Response rate and progression-free survival
To evaluate the objective response rate post XPE-A, and the progression- free survival and overall survival and quality of life.
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2010 (estimated)
- Study startDec 2010
- Primary completionJul 2011
- Study completionJul 2011
Why it stopped: PI relocated to another institution. No subjects went on treatment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck NeoplasmsStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01262859
- Sponsor's protocol ID
- 09-039
- Other IDs
- UPCI 09-039
- Status last verified
- Jan 2014
- First submitted
- 16 Dec 2010
- Last updated
- 13 Jan 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot 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
- ClinicalTrials.gov ID
- NCT01262859
- Acronym / sponsor ID
- 09-039
- Conditions
- Head and Neck Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI relocated to another institution. No subjects went on treatment.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Dec 2010
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 17 Dec 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Induction chemotherapy is gaining momentum in the management of locally advanced squamous cell carcinoma of the head and neck (SCCHN). The combination of docetaxel, cisplatin, and 5-FU (TPF) was superior compared with PF in a Phase III clinical trials73,74. We have completed a Phase II clinical trial that showed that docetaxel, cisplatin, and cetuximab (TPE) is highly active and well tolerated as induction chemotherapy in SCCHN (Argiris et al. ASCO 2008; A6002). Preliminary survival results are very encouraging. 39 patients were enrolled and with median follow up 26 months the 2-year PFS was 70% and the 2-year OS 84%.The combination of chemotherapy plus cetuximab is already a standard treatment in recurrent or metastatic SCCHN47. Therefore, TPE can be used as the platform for the addition of novel agents.
EGFR and VEGF are among the most important and validated molecular targets in cancer therapy. The incorporation of novel targeted therapies to chemotherapy and radiotherapy is of particular interest in head and neck cancer, and may improve efficacy without significantly increasing toxicity. A Phase III trial of carboplatin/paclitaxel/bevacizumab with or without cetuximab in advanced NSCLC has been proposed by SWOG. Bevacizumab is currently being investigated in SCCHN with promising results. A Phase II study investigating the combination of pemetrexed and bevacizumab (UPCI 05-002) as well as a Phase II trial of cetuximab and bevacizumab (UPCI 05-087) in recurrent or metastatic SCCHN are ongoing at the University of Pittsburgh with encouraging results (ASCO 2008 and ASCO 2009). In this study, 32 have been already enrolled. There was only 1 patient with grade 3 hemorrhage. The objective response rate is 20%, the median PFS 2.8 months and the median OS 8.1 months.
In order to further improve the efficacy of TPE and the rate of complete responses we propose to add bevacizumab to the TPE followed by XPE regimen we developed at the University of Pittsburgh. Due to non-overlapping toxicities and based on our prior experience we anticipate that the regimen will be well tolerated. Moreover, we plan to obtain tumor biopsies and blood samples in the first cycle and evaluate the modulation of biomarkers post combination therapy. Data from induction with TPE (presented at ASCO 2009) indicate the potential significance of cytokine levels in patient outcome. Also, we will evaluate the feasibility of subsequent concurrent radiation, cisplatin, cetuximab and bevacizumab. Patients with stable disease in the primary could be considered candidates to surgical resection at the discretion of their physician, if the tumor is resectable.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study Intervention | Experimental | Drug: bevacizumabInduction 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patients with AJCC 6th 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.
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bevacizumabAlso: AvastinBevacizumab, 15 mg/kg IV over 30 minutes (if this infusion rate was well tolerated), every 3 weeks until completion of radiation The initial dose will be delivered over 90+/-15 minutes. If the first infusion is tolerated without infusion associated adverse events (fever and/or chills), the second infusion may be delivered over 60+/-10 minutes. If the 60 minute infusion is well tolerated, all subsequent infusions may be delivered over 30+/-10 minutes. | Drug | Study Intervention |
Primary outcome
Response rate
Time frame: 10 years
To evaluate the rate of complete responses with induction with cisplatin, docetaxel, cetuximab and bevacizumab (TPE-A) in patients with locally advanced head and neck cancer.
4 secondary outcomes
Serum Correlatives
Time frame: 10 years
Biomarkers
Time frame: 10 years
Toxicity
Time frame: 10 years
Response rate and progression-free survival
Time frame: 10 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing bevacizumab in people with Head and Neck Neoplasms, run by University of Pittsburgh 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: withdrawn, as of the sponsor's last update on 13 Jan 2014. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Response rate (time frame: 10 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Jan 2014.