Cancer
Conditions
Keywords
head, neck
Brief summary
The purpose of this study is to determine if the addition of a unique targeted agent called Cetuximab (also known as C225 and Erbitux) can increase the effectiveness of standard treatment with chemotherapy and radiation.
Detailed description
This research study involves the use of a combination of two chemotherapies, cisplatin and docetaxel, which have been known to shrink head and neck cancers and are a commonly used treatment for this type of cancer. This combination will then be followed by radiation and more chemotherapy. The purpose of this study is to see whether this combination of chemotherapy and radiation, with the addition of Cetuximab, can improve control of disease and collect information on what side effects this combination therapy may have. In addition, biologic factors (markers) will be studied that may help to predict and treat head and neck cancer patients in the future.
Interventions
DRUGDocetaxel
Docetaxel 75 mg/m\^2 IV over 1 hour, day 1
DRUGCisplatin
Cisplatin 75 mg/m\^2 IV over 1-2 hours, day 1, 1 hour following completion of cetuximab infusion.
DRUGCetuximab
Cetuximab dose will be 250 mg/m\^2 IV over 60 minutes weekly on ALL subsequent administrations (days 8 and 15 of cycle 1 and days 1,8,15 of cycles 2 and 3).
PROCEDURERadiation Therapy
Photon energies of 1.25 to 6 MV and/or appropriate electron energies for boosting the nodes are allowed. Photon energies\>6 MV may be utilized when appropriate to boost target localized centrally.
Sponsors
Bristol-Myers Squibb
University of Pittsburgh
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Stage III-IVB head and neck cancer, all sites, including unknown primary tumors (bulky stage II (T2N0) lesions of the base of tongue or hypopharynx and patients with stage II nasopharyngeal cancer are also eligible) Prior to study entry the resectability and alternative treatment options 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. Unequivocal demonstration of distant metastasis (M1) confers ineligibility 2. Histologically or cytologically confirmed diagnosis of squamous cell or poorly differentiated carcinomas, or WHO types I-III of the nasopharynx 3. Unidimensionally-measurable disease is required (RECIST) 4. 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 5. 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) 6. ECOG PS 0 or 1; 7. Organ & marrow function per protocol criteria and 8. Age of \>=18 years
Exclusion criteria
1. 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 2. Uncontrolled intercurrent illness or significant history of uncontrolled cardiac disease 3. Receiving any other investigational agents 4. No history of prior malignancy, with the exception of curatively treated squamous cell or basal carcinoma of the skin or in situ cervical cancer, or malignancy that has been treated with a curative intent with a 5-year disease-free survival 5. Significant baseline sensory or motor neurologic deficits (\> grade I neuropathy); 6. HIV-positive patients and 7. Prior severe infusion reaction to a monoclonal antibody.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 36 months | Objective response rate is defined as the percentage of participants with a best response of complete response or partial response. Disease assessments were based on Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 36 months | Objective response rate is defined as the percentage of participants with a best response of complete response or partial response. Disease assessments were based on Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0. |
| Progression-free Survival (PFS) | Up to 36 months | PFS is an estimated percentage of participants without disease progression at two years (or three years) after the start of study treatment. Progression was defined using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.0. The two-year and three-year PFS ended up being the same in this study. |
| 3-year Overall Survival (OS) | Up to 36 months | Three-year OS is an estimated percentage of participants still living at three years after the start of study treatment. |
| Quality of Life (QOL) | Pre-treatment, Post-induction, 3 months after XPE and 12 months after XPE | Effect of treatment on acute and late QOL and functional status using Functional Assessment of Cancer Therapy-General (FACT-G) with FACT-Head and Neck (FACT-HN) subscale. The instructions to the participant were: Below is a list of statements that other people with your illness have said are important. By circling one number per line, please indicate how true each statement has been for you during the past 7 days. The choices for each statement ranged from 0 (not at all) to 4 (very much). The FACT-G and FACT-Head and Neck total scores were computed by summing 27 and 39 questions respectively, for four subscales: physical well-being, social well-being, emotional well-being, and functional well-being. Questions for both assessments are phrased so that higher numbers/values indicate a better health state. |
| 2-year Overall Survival (OS) | Up to 24 months | Two-year OS is an estimated percentage of participants still living at two years after the start of study treatment. |
Other
| Measure | Time frame | Description |
|---|---|---|
| EGFR-related Serum Markers | Up to 36 months | Evaluation of changes in serum markers (EGFR-related) before and after therapy in the above patient population, and expression of pAKT, pMAPK, and other EGFR pathway-related markers as well angiogenesis biomarkers. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Head and Neck Cancer Patients Patients with locally advanced HNC, including squamous and undifferentiated histologies, treated with docetaxel 75 mg/m\^2 day 1, cisplatin 75 mg/m\^2 day 1, and cetuximab 250 mg/m\^2 days 1, 8, and 15 (after an initial loading dose of 400 mg/m\^2), termed TPE, repeated every 21 days for three cycles, followed by radiotherapy with concurrent cisplatin 30 mg/m\^2 and cetuximab weekly (XPE), and maintenance cetuximab for 6 months. | 39 |
| Total | 39 |
Baseline characteristics
| Characteristic | Head and Neck Cancer Patients |
|---|---|
| Age, Continuous | 55 years |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 39 / 39 |
| serious Total, serious adverse events | 32 / 39 |
Outcome results
Primary
Objective Response Rate (ORR)
Objective response rate is defined as the percentage of participants with a best response of complete response or partial response. Disease assessments were based on Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0.
Time frame: Up to 36 months
Population: Treated with docetaxel 75 mg/m\^2 day 1, cisplatin 75 mg/m\^2 day 1, and cetuximab 250 mg/m\^2 days 1, 8, and 15 (after an initial loading dose of 400 mg/m\^2), termed TPE, repeated every 21 days for three cycles.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Head and Neck Cancer Patients | Objective Response Rate (ORR) | 86 percentage of participants |
Secondary
2-year Overall Survival (OS)
Two-year OS is an estimated percentage of participants still living at two years after the start of study treatment.
Time frame: Up to 24 months
Population: All participants that started were evaluable for this outcome measure, except for the one patient removed from study due to hypersensitivity reaction on cycle 1, day 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Head and Neck Cancer Patients | 2-year Overall Survival (OS) | 84 percentage of participants |
Secondary
3-year Overall Survival (OS)
Three-year OS is an estimated percentage of participants still living at three years after the start of study treatment.
Time frame: Up to 36 months
Population: All participants that started were evaluable for this outcome measure, except for the one patient removed from study due to hypersensitivity reaction on cycle 1, day 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Head and Neck Cancer Patients | 3-year Overall Survival (OS) | 74 percentage of participants |
Secondary
Objective Response Rate (ORR)
Objective response rate is defined as the percentage of participants with a best response of complete response or partial response. Disease assessments were based on Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0.
Time frame: Up to 36 months
Population: Docetaxel 75 mg/m\^2 day 1, cisplatin 75 mg/m\^2 day 1, and cetuximab 250 mg/m\^2 days 1, 8, and 15 (after an initial loading dose of 400 mg/m\^2), termed TPE, repeated every 21 days for three cycles, followed by radiotherapy with concurrent cisplatin 30 mg/m\^2 and cetuximab weekly (XPE).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Head and Neck Cancer Patients | Objective Response Rate (ORR) | 100 percentage of participants |
Secondary
Progression-free Survival (PFS)
PFS is an estimated percentage of participants without disease progression at two years (or three years) after the start of study treatment. Progression was defined using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.0. The two-year and three-year PFS ended up being the same in this study.
Time frame: Up to 36 months
Population: All participants that started were evaluable for this outcome measure, except for the one patient removed from study due to hypersensitivity reaction on cycle 1, day 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Head and Neck Cancer Patients | Progression-free Survival (PFS) | two-year PFS | 70 percentage of participants |
| Head and Neck Cancer Patients | Progression-free Survival (PFS) | three-year PFS | 70 percentage of participants |
Secondary
Quality of Life (QOL)
Effect of treatment on acute and late QOL and functional status using Functional Assessment of Cancer Therapy-General (FACT-G) with FACT-Head and Neck (FACT-HN) subscale. The instructions to the participant were: Below is a list of statements that other people with your illness have said are important. By circling one number per line, please indicate how true each statement has been for you during the past 7 days. The choices for each statement ranged from 0 (not at all) to 4 (very much). The FACT-G and FACT-Head and Neck total scores were computed by summing 27 and 39 questions respectively, for four subscales: physical well-being, social well-being, emotional well-being, and functional well-being. Questions for both assessments are phrased so that higher numbers/values indicate a better health state.
Time frame: Pre-treatment, Post-induction, 3 months after XPE and 12 months after XPE
Population: Analysis was completed using all responses actually obtained.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Head and Neck Cancer Patients | Quality of Life (QOL) | FACT-G Total Score Pre-treatment | 77.4311 units on a scale | Standard Deviation 16.56741 |
| Head and Neck Cancer Patients | Quality of Life (QOL) | FACT-G Total Score Post-induction | 75.6303 units on a scale | Standard Deviation 15.68977 |
| Head and Neck Cancer Patients | Quality of Life (QOL) | FACT-G Total Score 3 months after XPE | 71.3864 units on a scale | Standard Deviation 17.51042 |
| Head and Neck Cancer Patients | Quality of Life (QOL) | FACT-G Total Score 12 months after XPE | 86.6702 units on a scale | Standard Deviation 18.82226 |
| Head and Neck Cancer Patients | Quality of Life (QOL) | FACT-HN Pre-treatment | 25.7000 units on a scale | Standard Deviation 6.7423 |
| Head and Neck Cancer Patients | Quality of Life (QOL) | FACT-HN Post-induction | 25.1250 units on a scale | Standard Deviation 7.42332 |
| Head and Neck Cancer Patients | Quality of Life (QOL) | FACT-HN 3 months after XPE | 19.4545 units on a scale | Standard Deviation 5.01167 |
| Head and Neck Cancer Patients | Quality of Life (QOL) | FACT-HN 12 months after XPE | 24.5263 units on a scale | Standard Deviation 7.50088 |
Other Pre-specified
EGFR-related Serum Markers
Evaluation of changes in serum markers (EGFR-related) before and after therapy in the above patient population, and expression of pAKT, pMAPK, and other EGFR pathway-related markers as well angiogenesis biomarkers.
Time frame: Up to 36 months