Head and Neck Cancer
Conditions
Keywords
Head and Neck Cancer, Cetuximab, Erbitux, Paclitaxel, Extreme, Metastatic, Recurrent
Brief summary
Treatment of recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) after progression to first line EXTREME-type treatment in patients undergoing maintenance treatment with cetuximab.
Interventions
DRUGPaclitaxel
Paclitaxel 80 mg/m2 may be infused, intravenously, every week.
Cetuximab 250 mg/m2 and Paclitaxel 80 mg/m2, both may be infused intravenously, every week. Cetuximab will be administered prior to paclitaxel.
Sponsors
Merck Sharp & Dohme LLC
Pivotal S.L.
Grupo Español de Tratamiento de Tumores de Cabeza y Cuello
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Signed the informed consent 2. Age ≥ 18 and \< 75 y 3. ECOG (Eastern Cooperative Oncology Group)performance status: 0-1 4. Life expectancy of at least 12 weeks 5. Histological or cytological confirmation of head & neck squamous cell carcinoma with localization in larynx, oropharynx, oral cavity or hypopharynx. 6. Having received at least 2 cycles of EXTREME-type chemotherapy (cisplatin or carboplatin + fluoropyrimidines + cetuximab) and being in maintenance phase with cetuximab because of having reached CR (Complete response), PR (Partial response) or SD (Stable disease) to said treatment 7. At least one measureable lesion by CT scan or MRI 8. Adequate bone marrow, liver and kidney function, according to: * Hb (Hemoglobin) ≥ 9.0 g/dl * Platelets 100,000/mm3 * ANC (Absolute Neutrophil Count) ≥ 1,500/mm3 * Total bilirubin ≤ 2 times the UNL * SGPT/ALT and SGOT/AST ≤ 3 x UNL (Upper normal limit) * Alkaline phosphatase ≤ 2.5 x UNL * Serum creatinine ≤ 1.5 times the ULN or creatinine clearance \> 50 ml/min 9. Adequate nutritional status: weight loss \< 20% in relationship to usual weight or albumin ≥ 35 g/l, in the last 12 w 10. Seric calcium adjusted to albumine lower or equal to 1,25 UNL. 11. Toxicity, due to previous treatment received, resolved to grade 1, before enrolment in the study 12. Women of childbearing potential should have a (-)ve pregnancy test in serum or urine,7 d before randomization. Postmenopausal women should have remained amenorrheic for at least 12 m. Furthermore, all men as well as women who participate in this study should use effective contraceptive methods beginning with the signing of the informed consent form and up to at least 6 m after the completion of the study or of the last dose, whichever occurs first
Exclusion criteria
1. Treatment for recurrent and/or metastatic disease other than the EXTREME- type first line (cisplatin or carboplatin + fluoropyrimidines + cetuximab) 2. Non-measurable lesion as only evidence of disease 3. Nasopharyngeal carcinoma 4. Clinical or radiographic evidence of brain metastases 5. Having history of or presenting clinically significant cardiovascular disease, such as, but not limited to, congestive heart failure, ≥ grade II of the NYHA, severe cardiac arrhythmias that require medication, or ≥ grade II peripheral vascular disease. Furthermore, those patients who have suffered myocardial infarction or unstable angina in the year prior to the onset of the study treatment or a recent onset angina in the last 3 m will also be excluded 6. History of or current presence of grade \>1 peripheral neuropathy 7. History of active neurological disease 8. History of uncontrolled convulsive episode 9. Current ≥ 2 grade infection 10. Known infection by HIV or chronic infection by HBV or HBC or presence of uncontrolled and severe intercurrent infections or other severe and uncontrolled concomitant diseases 11. History of uncontrolled diabetes, uncontrolled HBP or hepatic condition. 12. History of pulmonary fibrosis, acute pulmonary damage or interstitial pneumonia 13. Any antineoplastic treatment within the 4 w prior to the randomization period 14. History of another neoplastic disease during the last 5 y, with the exception of cured in situ basal cell ca.skin carcinoma, in situ ca.bladder, in situ ca.cervix and in situ ca.prostate 15. Known allergy or suspicion of allergy or hypersensitivity to any component of cetuximab or paclitaxel 16. Previous treatment with monoclonal antibodies or other signal transduction inhibitors or EGFR-targeted treatment (Except for previous treatment with cetuximab) 17. Known drug abuse (exception Alcoholism) 18. Any important and uncontrolled medical, psychological, psychiatric, geographic or social problem that may interfere in the participation of the subject in the study and that does not allow for adequate follow-up and compliance with the protocol and evaluation of the study results 19. Women who are pregnant or in breast-feeding period 20. Use of any investigational new drug within the 4 w prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Through study completion. The study was prematurely closed at 19 months due to lack of accrual. The primary endopoint was not analyzed. | The primary endpoint was to select the most effective treatment arm based on the progression-free survival (PFS) reached in each treatment arm. This was defined as the time elapsed from inclusion in the study until the date when disease progression or death (for any cause) was documented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Through study completion. The study was prematurely closed at 19 months due to lack of accrual. The secondary endopoint was not analyzed. | Calculate overall survival (OS) in both arms |
| Percentage of Objective Response | Through study completion. The study was prematurely closed at 19 months due to lack of accrual. Neither the primary nor the secondary endopoints were analyzed. | Calculate the percentage of objective responses (OR), following the new RECIST criteria, obtained in both arms |
| Participants With Adverse Events | The duration of the study (Nineteen months) and until the last patient included completed one year of follow up / died or was lost to FU. Adverse events were registered from study entry until 60 days after receiving the last dose of study drug. | To perform a descriptive analysis of the adverse events observed in the patients included in the study. Further analysis could not be performed due to early closure of this study due to lack of accrual. Adverse events were registered from study entry until 60 days after receiving the last dose of study drug. |
| Treatment Compliance | 3 years | Evaluate treatment compliance rate in both treatment arms, in order to analyze it, the dose intensity would be calculated as the quantity of each of the administered study drugs per unit of time (mg/m2/week) regardless of the treatment arm. To analyze the relative dose intensity, the dose of each administered drug will be divided per a unit of time and the planned quantity of each drug according to the doses described in the protocol. |
Participant flow
Recruitment details
The study was carried out in 10 academic medical centers in Spain. First patient in was on 16-February-2011 and the study was closed (last patient in) on 02-October-2012.
Participants by arm
| Arm | Count |
|---|---|
| Paclitaxel Paclitaxel 80 mg/m2 may be infused, intravenously, every week.
Paclitaxel: Paclitaxel 80 mg/m2 may be infused, intravenously, every week. | 9 |
| Cetuximab + Paclitaxel Cetuximab 250 mg/m2 and Paclitaxel 80 mg/m2, both may be infused intravenously, every week. Cetuximab will be administered prior to paclitaxel.
Cetuximab + Paclitaxel: Cetuximab 250 mg/m2 and Paclitaxel 80 mg/m2, both may be infused intravenously, every week. Cetuximab will be administered prior to paclitaxel. | 8 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Paclitaxel | Cetuximab + Paclitaxel | Total |
|---|---|---|---|
| Age, Continuous | 63.16 years STANDARD_DEVIATION 7.25 | 58.48 years STANDARD_DEVIATION 8.76 | 60.96 years STANDARD_DEVIATION 8.11 |
| Region of Enrollment Spain | 9 Participants | 8 Participants | 17 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 9 | 4 / 8 |
| other Total, other adverse events | 9 / 9 | 8 / 8 |
| serious Total, serious adverse events | 4 / 9 | 4 / 8 |
Outcome results
Primary
Progression Free Survival (PFS)
The primary endpoint was to select the most effective treatment arm based on the progression-free survival (PFS) reached in each treatment arm. This was defined as the time elapsed from inclusion in the study until the date when disease progression or death (for any cause) was documented.
Time frame: Through study completion. The study was prematurely closed at 19 months due to lack of accrual. The primary endopoint was not analyzed.
Population: Only 17 patients out of a planned protocol number of 80 were recruited to the study, owing to premature closure of the study. Two of those patients did not meet some of the inclusion and/or exclusion criteria. Database lock: 3 June 2013. There were insufficient numbers of patients to be able to analyse the efficacy endpoints.~The possible discrepancies that were pending resolution have been closed as Premature closure of the study. Deviation DN13/024.~.
Secondary
Overall Survival
Calculate overall survival (OS) in both arms
Time frame: Through study completion. The study was prematurely closed at 19 months due to lack of accrual. The secondary endopoint was not analyzed.
Population: Only 17 patients out of a planned protocol number of 80 were recruited to the study, owing to premature closure of the study (Database lock: 3 June 2013). There were insufficient numbers of patients to be able to analyse the secondary endpoints.~The possible discrepancies that were pending resolution have been closed as Premature closure of the study. Deviation DN13/024.
Secondary
Participants With Adverse Events
To perform a descriptive analysis of the adverse events observed in the patients included in the study. Further analysis could not be performed due to early closure of this study due to lack of accrual. Adverse events were registered from study entry until 60 days after receiving the last dose of study drug.
Time frame: The duration of the study (Nineteen months) and until the last patient included completed one year of follow up / died or was lost to FU. Adverse events were registered from study entry until 60 days after receiving the last dose of study drug.
Population: This safety analysis includes all 17 patients (Database lock: 3 June 2013). There were insufficient numbers of patients to be able to analyse the efficacy endpoints.~The possible discrepancies that were pending resolution have been closed as Premature closure of the study. Deviation DN13/024.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paclitaxel | Participants With Adverse Events | 9 participants |
| Cetuximab + Paclitaxel | Participants With Adverse Events | 8 participants |
Secondary
Percentage of Objective Response
Calculate the percentage of objective responses (OR), following the new RECIST criteria, obtained in both arms
Time frame: Through study completion. The study was prematurely closed at 19 months due to lack of accrual. Neither the primary nor the secondary endopoints were analyzed.
Population: Only 17 patients out of a planned protocol number of 80 were recruited to the study, owing to premature closure of the study. Two of those patients did not meet some of the inclusion and/or exclusion criteria. Database lock: 3 June 2013. There were insufficient numbers of patients to be able to analyse the primary and secondary endpoints of the study
Secondary
Treatment Compliance
Evaluate treatment compliance rate in both treatment arms, in order to analyze it, the dose intensity would be calculated as the quantity of each of the administered study drugs per unit of time (mg/m2/week) regardless of the treatment arm. To analyze the relative dose intensity, the dose of each administered drug will be divided per a unit of time and the planned quantity of each drug according to the doses described in the protocol.
Time frame: 3 years
Population: Only 17 patients out of a planned protocol number of 80 were recruited to the study, owing to premature closure of the study (Database lock: 3 June 2013). There were insufficient numbers of patients to be able to analyse the primary and secondary endpoints.~The possible discrepancies that were pending resolution have been closed as Premature closure of the study. Deviation DN13/024.