Head and Neck Cancer, Recurrent Disease, Squamous Cell Carcinoma
Conditions
Keywords
SCCHN, Head and Neck Cancer, Squamous Cell Carcinoma, Recurrent
Brief summary
Whether low-dose radiation in addition to Taxotere and Erbitux improves the response rate of patients with recurrent unresectable head and neck squamous cell carcinoma.
Detailed description
The investigator's approach is based on the following reasons: * Low dose hyper-radiation sensitivity response will be significantly enhanced in Taxotere- induced G2/M cell cycle arrest. * LDFRT will render enhanced bax activation mediated mode of cell death. * Erbitux will arrest the cells in G1/G0 phase leading to p21-mediated mode of cell death. * The toxicity profile is expected to be minimal. Based on the above mentioned reasons, we propose this novel schema of treatment in recurrent SCCHN.
Interventions
DRUGErbitux
Erbitux: 400 mg/m2 as a loading dose one week prior to radiation and taxotere, and then at 250 mg/m2 given weekly on Day 1 of treatment week following Taxotere.
DRUGTaxotere
Taxotere : 20 mg/m2 IV once a week on Day 1 during treatment weeks 2 to 7.
RADIATIONLow Dose Fractionated Radiation Therapy
Low-dose fractionated Radiation (LDFRT): 0.5 Gy per fraction twice-a-day (BID) at least 6 to 8 hours apart on Days 2 and 3 of treatment weeks 2 to 7 for a total dose of 12 Gy.
Sponsors
University of Miami
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Patients must have pathologically confirmed recurrence (reappearance of previously cleared) squamous cell cancer primary in the upper aerodigestive tract .Patients may have experienced more than one recurrence as long as the first recurrence occurred ≥ 6 months following the end of the prior RT. 2. The recurrence must have defined bi- or uni-dimensional measurements. 3. Recurrence must be confined to the head and neck above the clavicles (loco-regional recurrence). 4. The patient must not be a candidate for surgical resection. 5. Patients must be at least 6 months from completion of prior chemotherapy and radiation therapy. 6. Patients may have received prior chemotherapy as a component of their primary treatment, but not for recurrent disease. 7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. 8. Granulocytes ≥ 1500/mm3, platelets ≥ 100,000/mm3, serum bilirubin ≤ 1.5 mg/dl, creatinine \< 1.5 mg/dl within 3 weeks prior to registration. 9. Liver Function Tests (LFTs) ≤ 2 x normal (serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic-pyruvic transaminase (SGPT)/Alkaline Phosphatase). If \> 2 x normal, liver ultrasound or CT is required to exclude metastases. If negative for metastases, patients are eligible. 10. Patients must sign a study-specific informed consent form prior to study entry.
Exclusion criteria
1. Distant metastases outside of the head and neck. 2. Primary disease in the nasopharynx or the salivary gland. 3. Other concurrent invasive malignancies. 4. Prior invasive malignancy unless disease free for at least two years (except prior in situ malignancies, e.g. cervix, breast, non-melanomatous skin cancer, etc. are permissible). 5. Intercurrent medical illnesses which would impair patient tolerance to therapy or limit survival. 6. Pre-existing grade ≥ 2 peripheral sensory neuropathy 7. Pregnant and nursing women are excluded because of the potential teratogenic effects and potential unknown effects on nursing newborns. 8. Prior history of sever hypersensitivity reaction to Docetaxol, Cetuximab or a drug with formulated with Polysorbate 80.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) of Participants | Up to 6 months from End of Treatment, about 9 months | ORR is defined as the rate of study participants achieving complete response (CR) or partial response (PR) to protocol therapy according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Study Participants Experiencing Treatment-Related Toxicity | Up to 6 years | Assess the safety profile (acute and late toxicities) of the proposed treatment. Number of study participants experiencing treatment-related acute and late toxicity: * Acute toxicity is defined as toxicity occurring within 90 days of start of therapy. * Late/Long-term toxicity defined as toxicity occurring more than 90 days after start of therapy. |
| Estimated Progression-Free Survival (PFS) | Up to 6 years | Progression-free survival (PFS) is defined of the length of time from the start date of treatment to the earliest documented occurrence of disease progression according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) criteria. In the absence of an event constituting failure, follow up time will be censored at the date of last disease assessment. |
| Estimated Overall Survival (OS) | Up to 6 years | Overall survival (OS) is defined as the length of time from the start of treatment that study participants diagnosed with the disease are still alive. OS will be measured from the start date of treatment to the date of death or last contact (censored observations). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Erbitux, Taxotere, LD Fractionated RT Erbitux, Taxotere and Low Dose Fractionated Radiation Therapy (LDFRT):
* Erbitux: 400 mg/m2 as a loading dose one week prior to radiation and taxotere, and then at 250 mg/m2 given weekly on Day 1 of treatment week following Taxotere.
* Taxotere: 20 mg/m2 IV once a week on Day 1 during treatment weeks 2 to 7.
* Low-dose fractionated Radiation (LDFRT): 0.5 Gy per fraction twice-a-day (BID) at least 6 to 8 hours apart on Days 2 and 3 of treatment weeks 2 to 7 for a total dose of 12 Gy. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Erbitux, Taxotere, LD Fractionated RT |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Chemotherapy | 3 Participants |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 4 Participants |
| Site of Head and Neck Carcinoma Floor of Mouth | 1 Participants |
| Site of Head and Neck Carcinoma Larynx | 2 Participants |
| Site of Head and Neck Carcinoma Tonsil | 1 Participants |
| Surgery | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 4 |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 1 / 4 |
Outcome results
Primary
Overall Response Rate (ORR) of Participants
ORR is defined as the rate of study participants achieving complete response (CR) or partial response (PR) to protocol therapy according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) criteria.
Time frame: Up to 6 months from End of Treatment, about 9 months
Population: Data for 4 of 5 participants analyzed due to 1 subject withdrawing prior to receiving protocol therapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erbitux, Taxotere, LD Fractionated RT | Overall Response Rate (ORR) of Participants | Overall Response (CR+PR), 1 month | 50 percentage of participants |
| Erbitux, Taxotere, LD Fractionated RT | Overall Response Rate (ORR) of Participants | Overall Response (CR+PR), 6 months | 0 percentage of participants |
| Erbitux, Taxotere, LD Fractionated RT | Overall Response Rate (ORR) of Participants | Complete Response (CR), 1 month | 0 percentage of participants |
| Erbitux, Taxotere, LD Fractionated RT | Overall Response Rate (ORR) of Participants | Complete Response (CR), 6 months | 0 percentage of participants |
| Erbitux, Taxotere, LD Fractionated RT | Overall Response Rate (ORR) of Participants | Partial Response (PR), 1 month | 50 percentage of participants |
| Erbitux, Taxotere, LD Fractionated RT | Overall Response Rate (ORR) of Participants | Partial Response (PR), 6 months | 0 percentage of participants |
| Erbitux, Taxotere, LD Fractionated RT | Overall Response Rate (ORR) of Participants | Stable Disease (SD), 1 month | 25 percentage of participants |
| Erbitux, Taxotere, LD Fractionated RT | Overall Response Rate (ORR) of Participants | Stable Disease (SD), 6 months | 0 percentage of participants |
| Erbitux, Taxotere, LD Fractionated RT | Overall Response Rate (ORR) of Participants | Progressive Disease (PD), 1 month | 25 percentage of participants |
| Erbitux, Taxotere, LD Fractionated RT | Overall Response Rate (ORR) of Participants | Progressive Disease (PD), 6 months | 100 percentage of participants |
Secondary
Estimated Overall Survival (OS)
Overall survival (OS) is defined as the length of time from the start of treatment that study participants diagnosed with the disease are still alive. OS will be measured from the start date of treatment to the date of death or last contact (censored observations).
Time frame: Up to 6 years
Population: At the time of study termination in June 2016, 1 patient had already died, 1 patient had refused follow-up, 1 patient was lost to follow-up and 1 patient was alive with disease. Overall survival data were not analyzed due to an insufficient number of evaluable participants accrued and early study termination for lack of efficacy.
Secondary
Estimated Progression-Free Survival (PFS)
Progression-free survival (PFS) is defined of the length of time from the start date of treatment to the earliest documented occurrence of disease progression according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) criteria. In the absence of an event constituting failure, follow up time will be censored at the date of last disease assessment.
Time frame: Up to 6 years
Population: At the time of study termination in June 2016, 1 patient had already died, 1 patient had refused follow-up, 1 patient was lost to follow-up and 1 patient was alive with disease. Progression-free survival data were not analyzed due to an insufficient number of evaluable participants accrued and early study termination for lack of efficacy.
Secondary
Number of Study Participants Experiencing Treatment-Related Toxicity
Assess the safety profile (acute and late toxicities) of the proposed treatment. Number of study participants experiencing treatment-related acute and late toxicity: * Acute toxicity is defined as toxicity occurring within 90 days of start of therapy. * Late/Long-term toxicity defined as toxicity occurring more than 90 days after start of therapy.
Time frame: Up to 6 years
Population: Data for 4 of 5 participants analyzed due to 1 subject withdrawing prior to receiving protocol therapy.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Erbitux, Taxotere, LD Fractionated RT | Number of Study Participants Experiencing Treatment-Related Toxicity | Acute Toxicities | 4 Participants |
| Erbitux, Taxotere, LD Fractionated RT | Number of Study Participants Experiencing Treatment-Related Toxicity | Late Toxicities | 0 Participants |