Squamous Cell CarcinomaPhase 2NCT00176267
Paclitaxel, Carboplatin And Low Dose Radiation As Induction Therapy In Locally Advanced Head And Neck Cancer
A Phase 2 study testing Radiotherapy, Paclitaxel and Carboplatin in people with Squamous Cell Carcinoma, run by Susanne Arnold.
Trial summary
This study is being performed utilizing two cycles of Paclitaxel and Carboplatin, plus low doses radiation as initial therapy prior to other treatment (surgery or radiation). The study is assessing if utilization of low doses radiation as a chemoenhancer will further increase the response rate seen with initial… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma
- What is being tested?
- Radiotherapy, Paclitaxel and Carboplatin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- No sites listed yet
- Study dates
- Sep 2002to 31 Jan 2017
- 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
- Adult patients greater than 18 years of age.
- ECOG performance status of 0, 1 or 2.
- Patients with pathologically documented bulky T2, III and IV SCCHN (excluding M1 disease), within 2 months of diagnosis. Bulky T2 tumors are defined as those that have a volume of disease greater than 35 cm3 as measured by CT or MRI scan (28).
- Patients will be medically fit for undergoing chemotherapy. Specifically:
- no evidence of active angina pectoris or ventricular arrhythmia's; no myocardial infarction within the last six months. (Patients with medically controlled hypertension or congestive heart failure are eligible.)
- an absolute neutrophil count of > 1000/uL and platelet count > 100,000/uL
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- serum total bilirubin < 1.5 mg/dL
- Creatinine Clearance greater than 60 ml/min
- Using an actual or calculated creatinine clearance using the formula:
- (140 - age)x(wgt in kg)/(serum creatinine)x(72) multiply by 0.85 for females
- if a pre-existing grade I neuropathy exists, patients must be willing to risk worsening neuropathy secondary to Paclitaxel. Patients with grade II or greater neuropathy will be excluded from study.
- ability to give written, informed consent to participate in the trial.
- Patients will have measurable disease as determined by MRI or CT scan or evaluable disease determined by panendoscopy or indirect laryngoscopy to be eligible for enrollment on this study.
Who cannot join
- Pregnant females. Males and women of childbearing potential must use effective contraception in order to prevent pregnancy during therapy.
- Patients with a history of previous or current malignancy at other sites diagnosed within the last 5 years, with the exception of adequately treated carcinoma in-situ of the cervix or basal or squamous cell carcinoma of the skin. Patients with a history of other malignancies, who remain free of recurrence or metastases for greater than five years are eligible.
- Patients with active infection will not be eligible for this protocol until the infection is treated and the symptoms have clinically resolved.
- Patients with a history of allergy to drugs utilizing Cremophor in the formulation.
- Prior chemotherapy, prior irradiation or surgery for SCCHN will not be allowed.
- Patients with metastatic disease will not be eligible for this study.
- Patients with grade II or greater peripheral neuropathy will be excluded from study.
About this study
This study is being performed utilizing two cycles of Paclitaxel and Carboplatin, plus low doses radiation as initial therapy prior to other treatment (surgery or radiation). The study is assessing if utilization of low doses radiation as a chemoenhancer will further increase the response rate seen with initial therapy.
Read the detailed description
Squamous cell cancers of the head and neck (SCCHN) comprise 5% of all cancers, with 40,000 new cases diagnosed annually. Surgery followed by irradiation or irradiation alone has been the standard of care for locally advanced Stage III and IV patients. With this approach, fewer than 30% of patients achieve long-term remission, and most recur locoregionally. Neoadjuvant chemotherapy has been administered prior to definitive therapy with response rates ranging from 60-90%, with pathologic CR rates documented in 30-70% of clinical responders. However, large randomized trials have shown no improvement in overall survival. Because induction chemotherapy alone does not appear to improve long-term disease free survival in advanced head and neck cancers, concomitant chemotherapy and radiation has been pursued in patients with locally advanced head and neck cancers. The concept of synergy between radiation and chemotherapy is well established in vitro. Various schedules of radiation and chemotherapy have been utilized including weekly chemotherapy during radiation, chemotherapy given every three weeks during radiation and alternating chemotherapy and radiation.
One novel approach to capitalizes on the synergy between radiation and chemotherapy is the use of low doses fractionated radiation (LDFRT) as a chemotherapy enhancer. In vitro data suggests that LDFRT enhances the response of both p53 wild type and p53 mutant cancer cell lines to chemotherapy. Not only was the cell death fraction increased, but there was no development of radioresistance in the cell lines studies when low doses of radiation were utilized. This strategy was translated into a clinical trial using four 80-cGy fractions of radiation with Carboplatin and Paclitaxel. Preliminary results have produced an impressive 85% response rate and this neoadjuvant regimen was safe and easy to deliver in patients with locally advanced SCCHN patients. In recently published work by Belani, a regimen using Carboplatin every four weeks combined with weekly Paclitaxel improved response rates in non-small cell lung cancer. The delivery of chemotherapy on a weekly schedule would be of particular benefit when adding LDFRT, because tumor cells could be exposed to LDFRT on multiple occasions per cycle of induction therapy, without the theoretic development of radioresistance. We propose to expand our understanding of LDFRT and chemotherapy by using two cycles of Paclitaxel and Carboplatin in a modification of the Belani regimen, plus LDFRT as induction therapy prior to definitive treatment (surgery or radiation). It is hoped that using LDFRT as a chemoenhancer will further increase the response rate seen with induction therapy in this population of patients.
- Conditions
- Squamous Cell Carcinoma
- Being tested
- Radiotherapy, Paclitaxel, Carboplatin
- Keywords
- head and neck, squamous cell carcinoma, squamous cell, carcinoma, paclitaxel, carboplatin, radiotherapy, induction therapy
- Medical subject headings
- Carcinoma, Squamous Cell, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RadiotherapyRadiation
50 cGy on days 1, 2, 8, 15, 22, 23, 29 \& 36 of chemotherapy
PaclitaxelDrug
75 mg/m2 intravenously over one hour on Days 1, 8, 15, 22, 29 and 36
CarboplatinDrug
AUC of 6 on Days 1 \& 22
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Radiation: Radiotherapy; Drug: Paclitaxel; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate
Measured: assessed at baseline and once between days 42 and 56, then repeated every 6 months until disease progression
Pathologic complete responses
Measured: assessed between 3 and 24 hours after the last dose of radiation
Secondary outcomes (3)
Toxicity
Measured: assessed starting day 1 through study completion day 56 or until toxicities resolve
Quality of Life
Measured: assessed pre-study and once between study days 42 and 56
Overall survival
Measured: throughout study treatment duration and then every 3 months after study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2005 (estimated)
- Study startSep 2002
- Primary completionJan 2005
- Study completion31 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Squamous Cell CarcinomaStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Susanne Arnold
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor-investigator, Susanne Arnold, University of Kentucky
- Investigators
- Susanne Arnold, MD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00176267
- Sponsor's protocol ID
- 02-H&N-15-BMS
- Status last verified
- May 2023
- First submitted
- 9 Sep 2005
- Last updated
- 1 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Paclitaxel, Carboplatin And Low Dose Radiation As Induction Therapy In Locally Advanced Head And Neck Cancer
- ClinicalTrials.gov ID
- NCT00176267
- Acronym / sponsor ID
- 02-H&N-15-BMS
- Conditions
- Squamous Cell Carcinoma
- Keywords
- head and neck, squamous cell carcinoma, squamous cell, carcinoma, paclitaxel, carboplatin, radiotherapy, induction therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Susanne ArnoldUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Sep 2002
- Primary completion
- Jan 2005 (actual)
- Study completion
- 31 Jan 2017 (actual)
- First posted
- 15 Sep 2005 (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.
This study is being performed utilizing two cycles of Paclitaxel and Carboplatin, plus low doses radiation as initial therapy prior to other treatment (surgery or radiation). The study is assessing if utilization of low doses radiation as a chemoenhancer will further increase the response rate seen with initial therapy.
Detailed description
Squamous cell cancers of the head and neck (SCCHN) comprise 5% of all cancers, with 40,000 new cases diagnosed annually. Surgery followed by irradiation or irradiation alone has been the standard of care for locally advanced Stage III and IV patients. With this approach, fewer than 30% of patients achieve long-term remission, and most recur locoregionally. Neoadjuvant chemotherapy has been administered prior to definitive therapy with response rates ranging from 60-90%, with pathologic CR rates documented in 30-70% of clinical responders. However, large randomized trials have shown no improvement in overall survival. Because induction chemotherapy alone does not appear to improve long-term disease free survival in advanced head and neck cancers, concomitant chemotherapy and radiation has been pursued in patients with locally advanced head and neck cancers. The concept of synergy between radiation and chemotherapy is well established in vitro. Various schedules of radiation and chemotherapy have been utilized including weekly chemotherapy during radiation, chemotherapy given every three weeks during radiation and alternating chemotherapy and radiation.
One novel approach to capitalizes on the synergy between radiation and chemotherapy is the use of low doses fractionated radiation (LDFRT) as a chemotherapy enhancer. In vitro data suggests that LDFRT enhances the response of both p53 wild type and p53 mutant cancer cell lines to chemotherapy. Not only was the cell death fraction increased, but there was no development of radioresistance in the cell lines studies when low doses of radiation were utilized. This strategy was translated into a clinical trial using four 80-cGy fractions of radiation with Carboplatin and Paclitaxel. Preliminary results have produced an impressive 85% response rate and this neoadjuvant regimen was safe and easy to deliver in patients with locally advanced SCCHN patients. In recently published work by Belani, a regimen using Carboplatin every four weeks combined with weekly Paclitaxel improved response rates in non-small cell lung cancer. The delivery of chemotherapy on a weekly schedule would be of particular benefit when adding LDFRT, because tumor cells could be exposed to LDFRT on multiple occasions per cycle of induction therapy, without the theoretic development of radioresistance. We propose to expand our understanding of LDFRT and chemotherapy by using two cycles of Paclitaxel and Carboplatin in a modification of the Belani regimen, plus LDFRT as induction therapy prior to definitive treatment (surgery or radiation). It is hoped that using LDFRT as a chemoenhancer will further increase the response rate seen with induction therapy in this population of patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Radiation: Radiotherapy, Drug: Paclitaxel, Drug: Carboplatin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Adult patients greater than 18 years of age.
- ECOG performance status of 0, 1 or 2.
- Patients with pathologically documented bulky T2, III and IV SCCHN (excluding M1 disease), within 2 months of diagnosis. Bulky T2 tumors are defined as those that have a volume of disease greater than 35 cm3 as measured by CT or MRI scan (28).
- Patients will be medically fit for undergoing chemotherapy. Specifically:
- (140 - age)x(wgt in kg)/(serum creatinine)x(72) multiply by 0.85 for females
Key exclusion criteria (7 listed)
- Pregnant females. Males and women of childbearing potential must use effective contraception in order to prevent pregnancy during therapy.
- Patients with a history of previous or current malignancy at other sites diagnosed within the last 5 years, with the exception of adequately treated carcinoma in-situ of the cervix or basal or squamous cell carcinoma of the skin. Patients with a history of other malignancies, who remain free of recurrence or metastases for greater than five years are eligible.
- Patients with active infection will not be eligible for this protocol until the infection is treated and the symptoms have clinically resolved.
- Patients with a history of allergy to drugs utilizing Cremophor in the formulation.
- Prior chemotherapy, prior irradiation or surgery for SCCHN will not be allowed.
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 |
|---|---|---|
| Radiotherapy50 cGy on days 1, 2, 8, 15, 22, 23, 29 \& 36 of chemotherapy | Radiation | 1 |
| Paclitaxel75 mg/m2 intravenously over one hour on Days 1, 8, 15, 22, 29 and 36 | Drug | 1 |
| CarboplatinAUC of 6 on Days 1 \& 22 | Drug | 1 |
Primary outcome
Response rate
Time frame: assessed at baseline and once between days 42 and 56, then repeated every 6 months until disease progression
Pathologic complete responses
Time frame: assessed between 3 and 24 hours after the last dose of radiation
3 secondary outcomes
Toxicity
Time frame: assessed starting day 1 through study completion day 56 or until toxicities resolve
Quality of Life
Time frame: assessed pre-study and once between study days 42 and 56
Overall survival
Time frame: throughout study treatment duration and then every 3 months after study completion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2023.
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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.
Susanne Arnold, MD principal investigator
University of Kentucky
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Radiotherapy, Paclitaxel and Carboplatin in people with Squamous Cell Carcinoma, run by Susanne Arnold.
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 13 inclusion and 7 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 1 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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: assessed at baseline and once between days 42 and 56, then repeated every 6 months until disease progression). The study lists 2 primary outcomes in all. 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 1 Jun 2023.