Head and Neck Cancer, Larynx
Conditions
Keywords
Cancer, Low dose radiation
Brief summary
The primary hypothesis of this study is that hyper-radiosensitivity (HRS) seen at extremely low doses of radiation can be exploited to enhance the effect of chemotherapy, and that this effect differs from the cellular effect of higher, standard fractions of radiation used in traditional radiation treatment paradigms.
Interventions
RADIATIONLow dose fractionated radiation - 80cGy with chemotherapy
Chemotherapy + 80 cGy of RT
DRUGDocetaxel and Carboplatin AUC 6
Docetaxel 75 mg/m2 and Carboplatin AUC 6 without Radiation
Sponsors
Susanne Arnold
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed locally advanced head and neck cancer of squamous type stage III, IVA and IV B and select Stage II tumors of the BOT who are appropriate for potentially curative therapy with chemoradiotherapy. * Measurable disease. * ECOG performance status of 0, 1 or 2 * No prior chemotherapy for the current locally advanced SCCHN. * Age ≥18 years. * Life expectancy of greater than 3 months * Normal organ and marrow function measured within 14 days of registration as defined below: * absolute neutrophil count ≥ 1,000/mcL * platelets ≥ 100,000/mcL * total bilirubin \< institutional upper limit of normal * AST(SGOT ≤ 2.5 × institutional upper limit of normal * Alkaline phosphatase ≤ 2.5 × institutional upper limit of normal * creatinine within normal institutional limits * OR o Creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, throughout the duration of active treatment and for 4 months after completion of chemotherapy and radiation. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of active study treatment, and for 4 months after completion of chemotherapy and radiation (both induction and definitive) administration. * Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
* Prior chemotherapy for SCCHN * Patients who are receiving any other investigational agents. * Patients with known brain metastases * History of allergic reactions attributed to compounds of similar chemical or biologic composition to Carboplatin or Docetaxel. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant women * HIV-positive patients on combination antiretroviral therapy * Other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated previous Stage I or II cancer from which the patient is currently in complete remission or other cancer from which the patient has been disease-free for 3 years. * Patients with nasopharynx or salivary gland primary site * Patients with distant metastatic disease (M1c) * Patients with grade II or greater peripheral neuropathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Site Complete Response Rate | Up to 50 days | Primary site is defined as the original, or first site that the cancer developed in the body. In this study, primary sites within the head and neck included squamous cancers of the larynx, oral cavity, oropharynx, hypopharynx.Complete response rate in patients treated with 2 cycles of induction Docetaxel and Carboplatin with low dose fractionated radiation therapy (LDFRT) will be compared to those treated with chemotherapy alone. CRR was determined Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Where possible, surgeon also evaluated primary site and provided response assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | Up to 50 days | To assess overall response rate of patients to 2 cycles of induction Docetaxel and Carboplatin with or without LDFRT. Response assessment was Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, and Progressive Disease (PD): \> 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). (Note: the appearance of one or more new lesions is also considered progression). |
| Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. | Up to 50 days (pre- and post-treatment) | Quality of Life (QOL) will be measured pre- and post-treatment using a single 5-question QOL well-being survey. The change in score will be presented independently for each subpart of the QOL survey. 1. Physical; scores range from 7-35; higher scores indicate increased well-being 2. Social/family; scores range from 7-35; higher scores indicate increased well-being 3. Emotional; scores range from 6-30; higher scores indicate increased well-being 4. Functional; scores range from 7-35; higher scores indicate increased well-being 5. Additional Concerns; scores range from 10-50; lower scores indicate increased well-being 6. FACT-G is the sum of the first 4 scores; scores range from 27-135; higher scores indicated increased well-being 7. FACT-H&N is the sum of the first five scores; scores range from 37-185; higher scores indicated increased well-being 8. Trial Outcome Index is the sum of 1, 4 and 5; scores range from 24-120; higher scores indicated increased well-being |
| 3-year Overall Survival | From date of randomization until date of death from any cause, assessed up to 3 years | 3-year overall survival |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy Plus Radiation Therapy Low dose fractionated radiation - 80cGy with chemotherapy
Low dose fractionated radiation - 80cGy with chemotherapy: Chemotherapy + 80 cGy of RT | 23 |
| Chemotherapy Without Radiation Chemotherapy only
Docetaxel and Carboplatin AUC 6: Docetaxel 75 mg/m2 and Carboplatin AUC 6 without Radiation | 22 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Chemotherapy Plus Radiation Therapy | Total | Chemotherapy Without Radiation |
|---|---|---|---|
| Age, Continuous | 58 years STANDARD_DEVIATION 6.7 | 57 years STANDARD_DEVIATION 7.4 | 55 years STANDARD_DEVIATION 8.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 44 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 44 Participants | 22 Participants |
| Region of Enrollment United States | 23 participants | 45 participants | 22 participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 2 Participants |
| Sex: Female, Male Male | 18 Participants | 38 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 22 | 9 / 20 |
| other Total, other adverse events | 22 / 22 | 20 / 20 |
| serious Total, serious adverse events | 12 / 22 | 6 / 20 |
Outcome results
Primary
Primary Site Complete Response Rate
Primary site is defined as the original, or first site that the cancer developed in the body. In this study, primary sites within the head and neck included squamous cancers of the larynx, oral cavity, oropharynx, hypopharynx.Complete response rate in patients treated with 2 cycles of induction Docetaxel and Carboplatin with low dose fractionated radiation therapy (LDFRT) will be compared to those treated with chemotherapy alone. CRR was determined Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Where possible, surgeon also evaluated primary site and provided response assessment.
Time frame: Up to 50 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy Plus Radiation Therapy | Primary Site Complete Response Rate | 6 Participants |
| Chemotherapy Without Radiation | Primary Site Complete Response Rate | 4 Participants |
Secondary
3-year Overall Survival
3-year overall survival
Time frame: From date of randomization until date of death from any cause, assessed up to 3 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy Plus Radiation Therapy | 3-year Overall Survival | 14 Participants |
| Chemotherapy Without Radiation | 3-year Overall Survival | 11 Participants |
Secondary
Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy.
Quality of Life (QOL) will be measured pre- and post-treatment using a single 5-question QOL well-being survey. The change in score will be presented independently for each subpart of the QOL survey. 1. Physical; scores range from 7-35; higher scores indicate increased well-being 2. Social/family; scores range from 7-35; higher scores indicate increased well-being 3. Emotional; scores range from 6-30; higher scores indicate increased well-being 4. Functional; scores range from 7-35; higher scores indicate increased well-being 5. Additional Concerns; scores range from 10-50; lower scores indicate increased well-being 6. FACT-G is the sum of the first 4 scores; scores range from 27-135; higher scores indicated increased well-being 7. FACT-H&N is the sum of the first five scores; scores range from 37-185; higher scores indicated increased well-being 8. Trial Outcome Index is the sum of 1, 4 and 5; scores range from 24-120; higher scores indicated increased well-being
Time frame: Up to 50 days (pre- and post-treatment)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chemotherapy Plus Radiation Therapy | Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. | PHYSICAL WELL-BEING SCORE | -1.46 change in score | Standard Deviation 5.12 |
| Chemotherapy Plus Radiation Therapy | Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. | FACT-G TOTAL SCORE | -1.23 change in score | Standard Deviation 13.52 |
| Chemotherapy Plus Radiation Therapy | Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. | EMOTIONAL WELL-BEING SCORE | 2.05 change in score | Standard Deviation 3.75 |
| Chemotherapy Plus Radiation Therapy | Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. | SOCIAL/FAMILY WELL-BEING SCORE | -1.34 change in score | Standard Deviation 4.55 |
| Chemotherapy Plus Radiation Therapy | Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. | FACT-H&N TOTAL SCORE | 3.79 change in score | Standard Deviation 18.05 |
| Chemotherapy Plus Radiation Therapy | Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. | FUNCTIONAL WELL-BEING SCORE | -0.48 change in score | Standard Deviation 6.04 |
| Chemotherapy Plus Radiation Therapy | Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. | TRIAL OUTCOME INDEX SCORE | 3.08 change in score | Standard Deviation 14.55 |
| Chemotherapy Plus Radiation Therapy | Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. | ADDITIONAL CONCERNS SCORE | 5.01 change in score | Standard Deviation 8.24 |
| Chemotherapy Without Radiation | Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. | TRIAL OUTCOME INDEX SCORE | 0.29 change in score | Standard Deviation 15.05 |
| Chemotherapy Without Radiation | Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. | PHYSICAL WELL-BEING SCORE | -1.64 change in score | Standard Deviation 7.22 |
| Chemotherapy Without Radiation | Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. | SOCIAL/FAMILY WELL-BEING SCORE | -2.34 change in score | Standard Deviation 3.72 |
| Chemotherapy Without Radiation | Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. | EMOTIONAL WELL-BEING SCORE | 1.60 change in score | Standard Deviation 4.31 |
| Chemotherapy Without Radiation | Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. | FUNCTIONAL WELL-BEING SCORE | -1.70 change in score | Standard Deviation 4.92 |
| Chemotherapy Without Radiation | Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. | FACT-G TOTAL SCORE | -4.08 change in score | Standard Deviation 12.72 |
| Chemotherapy Without Radiation | Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. | ADDITIONAL CONCERNS SCORE | 3.63 change in score | Standard Deviation 7.8 |
| Chemotherapy Without Radiation | Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. | FACT-H&N TOTAL SCORE | -0.46 change in score | Standard Deviation 19.16 |
Secondary
Overall Response Rate
To assess overall response rate of patients to 2 cycles of induction Docetaxel and Carboplatin with or without LDFRT. Response assessment was Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, and Progressive Disease (PD): \> 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). (Note: the appearance of one or more new lesions is also considered progression).
Time frame: Up to 50 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Chemotherapy Plus Radiation Therapy | Overall Response Rate | Overall Complete Response Rate | 1 Participants |
| Chemotherapy Plus Radiation Therapy | Overall Response Rate | Overall Partial Response Rate | 11 Participants |
| Chemotherapy Plus Radiation Therapy | Overall Response Rate | Overall Stable Disease Rate | 10 Participants |
| Chemotherapy Plus Radiation Therapy | Overall Response Rate | overall Progressive Disease Rate | 0 Participants |
| Chemotherapy Without Radiation | Overall Response Rate | overall Progressive Disease Rate | 0 Participants |
| Chemotherapy Without Radiation | Overall Response Rate | Overall Complete Response Rate | 1 Participants |
| Chemotherapy Without Radiation | Overall Response Rate | Overall Stable Disease Rate | 7 Participants |
| Chemotherapy Without Radiation | Overall Response Rate | Overall Partial Response Rate | 12 Participants |