Head and Neck Cancer
Conditions
Keywords
Quality of Life
Brief summary
Docetaxel and cetuximab are FDA-approved for the treatment of squamous cell carcinoma of the head and neck (SCCHN). Cisplatin and carboplatin, while not FDA-approved for SCCHN, have been used as standard of care in SCCHN patients in combination with other drugs. This study evaluates if weekly cisplatin and docetaxel, in combination with cetuximab, is effective in palliative treatment of patients with SCCHN. These drugs will be given intravenously weekly, repeated 3 of every 4 weeks until evidence of disease progression or unacceptable adverse events.
Detailed description
Primary Objective:To establish the response rate using RECIST 1 criteria to weekly TPC in patients with metastatic or relapsed squamous cell carcinoma of the head and neck Secondary Objective: To establish the safety profile, progression free and overall survival of weekly TPC in this patient population.
Interventions
DRUGDocetaxel
30 mg/m² by intravenous (IV) administration
DRUGCisplatin
30 mg/m² by intravenous (IV) administration
DRUGCetuximab
400 mg/m² by intravenous (IV) administration, thereafter 250 IV
DRUGCarboplatin
Area under the free carboplatin plasma concentration versus time curve (AUC)=2 by intravenous (IV) administration
Sponsors
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Squamous cell carcinoma (SCC) of head and neck (SCCHN), including all pharynx, larynx, oral cavity, skin and para-nasal sinus sites. Patients with SCC of unknown primary presenting in the neck clinically compatible with head and neck mucosal primary sites are eligible. * If prior chemoradiation, radiation, and/or surgery in the potentially curative setting, \> 3 months has elapsed since the end of the potentially curative treatment ended * If history of other malignancies treated curatively \> 1 year prior to enrollment, no evidence of relapse at the time of enrollment * If brain metastasis, central nervous system (CNS) imaging documents no evidence of CNS progression at least 30 days following definitive CNS treatment (resection or radiation) * ≥ 16 years old * Eastern cooperative oncology group (ECOG) Performance Status \< 3 * Laboratory value requirements at enrollment: * Absolute neutrophil count \> 1500/mm³ * Platelet count \> 100,000/mm³ * Hemoglobin \> 8 g/dL * Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) \< 2.5 x upper limit of normal (ULN) unless liver metastases documented. If so, AST and ALT \< 5 x ULN required. * Total bilirubin \< 1.5 x ULN, EXCEPT if Gilbert's syndrome is present. If so, total bilirubin \< 2.5 x ULN * Serum Creatinine \< 1.5 mg/dL OR an estimated creatinine clearance from 24 hour urine collection \> 50 mL/min * Peripheral neuropathy \< grade 2 * Hearing loss in best ear \< grade 2 per Chang criteria if audiogram performed. Formal audiology is not required in patients with no clinical evidence of hearing loss at baseline. * Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
* Prior palliative chemotherapy * Active infections including HIV (EXCEPTION: HIV-positive patients on HAART with undetectable blood HIV levels, or with history or serological evidence of exposure to Hepatitis B without active infection are eligible) * Prior grade 3 allergic or infusion reactions to docetaxel, cisplatin or cetuximab (EXCEPTION: a history of infusion reactions that were well-tolerated, at physician's discretion) * Pregnant and/or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | 8 weeks | Clinical response for each participant will be assessed after 8 weeks of treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Overall response rate (ORR) was assessed as the sum of the number of participants that experience a complete response (CR) or partial response (PR). The outcome is defined and reported as the number of subjects that responded, a number without dispersion. Other response statuses are included. RECIST v1.1 criteria is defined as follows. * 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 * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | 24 months | Progression-free survival (PFS), defined as the duration of time from start of treatment to time of progression or death, was assessed through 24 months, according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. The outcome is reported as the median time that participants remained free of progression, with 95% confidence interval (CI). * 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 * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria |
| Overall Survival (OS) | 24 months | Overall survival (OS) was assessed through 24 months. The outcome is reported as the median time that participants remained alive, with 95% CI. |
| Grade 3, 4, and 5 Related Adverse Events (Toxicities) | 2 years | Related adverse events are considered toxicities. The outcome was assessed as adverse events and serious adverse events (SAEs per 21CFR§312.32) at least Grade 3, and are reported as the number of toxicities by grade (3, 4 or 5), a number without dispersion. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cisplatin + Docetaxel + Cetuximab Patients will be treated weekly with cisplatin, docetaxel, and cetuximab.
Docetaxel: 30 mg/m² by intravenous (IV) administration
Cisplatin: 30 mg/m² by intravenous (IV) administration
Cetuximab: 400 mg/m² by intravenous (IV) administration, thereafter 250 IV
Carboplatin: Area under the free carboplatin plasma concentration versus time curve (AUC)=2 by intravenous (IV) administration | 27 |
| Total | 27 |
Baseline characteristics
| Characteristic | Cisplatin + Docetaxel + Cetuximab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Age, Continuous | 57.1 years STANDARD_DEVIATION 14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment United States | 27 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 13 / 27 |
| other Total, other adverse events | 27 / 27 |
| serious Total, serious adverse events | 27 / 27 |
Outcome results
Primary
Overall Response Rate (ORR)
Clinical response for each participant will be assessed after 8 weeks of treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Overall response rate (ORR) was assessed as the sum of the number of participants that experience a complete response (CR) or partial response (PR). The outcome is defined and reported as the number of subjects that responded, a number without dispersion. Other response statuses are included. RECIST v1.1 criteria is defined as follows. * 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 * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria
Time frame: 8 weeks
Population: Response data were not available for all participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cisplatin + Docetaxel + Cetuximab | Overall Response Rate (ORR) | Complete Response (CR) | 1 participants |
| Cisplatin + Docetaxel + Cetuximab | Overall Response Rate (ORR) | Partial Response (PR) | 14 participants |
| Cisplatin + Docetaxel + Cetuximab | Overall Response Rate (ORR) | Overall Response (OR) | 15 participants |
| Cisplatin + Docetaxel + Cetuximab | Overall Response Rate (ORR) | Stable disease (SD) | 5 participants |
| Cisplatin + Docetaxel + Cetuximab | Overall Response Rate (ORR) | Progressive disease (PD) | 6 participants |
Secondary
Grade 3, 4, and 5 Related Adverse Events (Toxicities)
Related adverse events are considered toxicities. The outcome was assessed as adverse events and serious adverse events (SAEs per 21CFR§312.32) at least Grade 3, and are reported as the number of toxicities by grade (3, 4 or 5), a number without dispersion.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cisplatin + Docetaxel + Cetuximab | Grade 3, 4, and 5 Related Adverse Events (Toxicities) | 24 Related Adverse Events |
Secondary
Overall Survival (OS)
Overall survival (OS) was assessed through 24 months. The outcome is reported as the median time that participants remained alive, with 95% CI.
Time frame: 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cisplatin + Docetaxel + Cetuximab | Overall Survival (OS) | 14.7 months |
Secondary
Progression-free Survival (PFS)
Progression-free survival (PFS), defined as the duration of time from start of treatment to time of progression or death, was assessed through 24 months, according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. The outcome is reported as the median time that participants remained free of progression, with 95% confidence interval (CI). * 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 * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria
Time frame: 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cisplatin + Docetaxel + Cetuximab | Progression-free Survival (PFS) | 4.8 months |