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Paclitaxel, Carboplatin And Low Dose Radiation As Induction Therapy In Locally Advanced Head And Neck Cancer


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Squamous Cell Carcinoma

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Trial Information

Paclitaxel, Carboplatin And Low Dose Radiation As Induction Therapy In Locally Advanced Head And Neck Cancer


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.


Inclusion Criteria:



1. Adult patients greater than 18 years of age.

2. ECOG performance status of 0, 1 or 2.

3. 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).

4. Patients will be medically fit for undergoing chemotherapy. Specifically:

1. 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.)

2. an absolute neutrophil count of > 1000/uL and platelet count > 100,000/uL

3. serum total bilirubin < 1.5 mg/dL

4. 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

5. 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.

6. ability to give written, informed consent to participate in the trial.

5. 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.

Exclusion Criteria:

1. Pregnant females. Males and women of childbearing potential must use effective
contraception in order to prevent pregnancy during therapy.

2. 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.

3. Patients with active infection will not be eligible for this protocol until the
infection is treated and the symptoms have clinically resolved.

4. Patients with a history of allergy to drugs utilizing Cremophor in the formulation.

5. Prior chemotherapy, prior irradiation or surgery for SCCHN will not be allowed.

6. Patients with metastatic disease will not be eligible for this study.

7. Patients with grade II or greater peripheral neuropathy will be excluded from study.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate

Outcome Time Frame:

assessed at baseline and once between days 42 and 56, then repeated every 6 months until disease progression

Safety Issue:

No

Principal Investigator

Susanne Arnold, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Kentucky

Authority:

United States: Institutional Review Board

Study ID:

02-H&N-15-BMS

NCT ID:

NCT00176267

Start Date:

September 2002

Completion Date:

Related Keywords:

  • Squamous Cell Carcinoma
  • head and neck
  • squamous cell carcinoma
  • squamous cell
  • carcinoma
  • paclitaxel
  • carboplatin
  • radiotherapy
  • induction therapy
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms

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