Head and Neck Cancer
Conditions
Keywords
Recurrent, stage IV, squamous cell carcinoma, hypopharynx, larynx, lip, oral cavity, nasopharynx, oropharynx, paranasal, nasal cavity, metastatic, neck cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as gemcitabine and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving gemcitabine together with paclitaxel may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving gemcitabine together with paclitaxel works in treating patients with persistent, recurrent, or metastatic head and neck cancer.
Detailed description
OBJECTIVES: * Determine overall and progression-free survival probability in patients with persistent, recurrent, or metastatic squamous cell carcinoma of the head and neck treated with gemcitabine and paclitaxel. * Determine the confirmed and unconfirmed response (partial and complete) probability in patients with measurable disease treated with this regimen. * Determine the toxicity of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive gemcitabine IV over 30 minutes and paclitaxel IV over 1 hour on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) receive 4 additional courses beyond CR. Patients are followed every 8 weeks until disease progression, every 6 month for 2 years, and then annually for 1 year. PROJECTED ACCRUAL: A total of 65 patients will be accrued for this study within 10-13 months.
Interventions
DRUGgemcitabine
3,000 mg/m2 IV over 30 minutes on days 1 and 15 (q28 days).
DRUGpaclitaxel
150 mg/m2 IV over 1 hour on days 1 and 15 (q 28 day cycle), administered after gemcitabine
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
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
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed squamous cell carcinoma of the head and neck (SCCHN) * Recurrent, persistent, or newly diagnosed metastatic disease * Measurable or non-measurable disease * No active or prior CNS metastasis PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Zubrod 0-1 Life expectancy * Not specified Hematopoietic * Not specified Hepatic * Not specified Renal * Not specified Other * No serious organ dysfunction * No serious comorbid conditions that would preclude study treatment * No history of hypersensitivity reaction to products containing polysorbate 80 * No active infection requiring systemic antibiotic therapy * No symptomatic sensory neuropathy ≥ grade 2 * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * Not pregnant or nursing * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent biologic or immunotherapy for SCCHN * No concurrent gene therapy for SCCHN Chemotherapy * No prior chemotherapy for recurrent or newly diagnosed metastatic disease * At least 6 months since prior induction or adjuvant chemotherapy * No more than 1 prior induction or adjuvant regimen * No prior gemcitabine or taxanes as part of induction, adjuvant, or neoadjuvant chemotherapy * No other concurrent chemotherapy for SCCHN Endocrine therapy * Not specified Radiotherapy * At least 28 days since prior radiotherapy and recovered * No concurrent radiotherapy for SCCHN Surgery * Not specified Other * No other concurrent therapy for SCCHN
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 0 - 3 years | Measured from time of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 0 - 3 years | Measured from date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact. |
| Response | 9 weeks - 3 years | Complete Response (CR) is complete disappearance of all measurable and non-measurable disease. No new lesions. No disease related symptoms. Normalization of markers and other normal lab values. Partial Response (PR) is greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. Confirmation of CR or PR means a repeat scan at least 4 weeks apart documented before progression or symptomatic deterioration. |
| Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Patients were assessed for adverse events after the first cycle of treatment and then every three months while on treatment. | Adverse Events (AEs) are reported by the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gemcitabine and Paclitaxel Patients received Gemcitabine 3,000 mg/m2 (IV on days 1 and 15 over 30 minutes) and Paclitaxel 150 mg/m2 (IV on days 1 and 15 over one hour). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) receive 4 additional courses beyond CR. Eligible patients who received any treatment were included in baseline measures. | 63 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 10 |
| Overall Study | Death | 2 |
| Overall Study | Ineligible | 3 |
| Overall Study | Never received treatment | 1 |
| Overall Study | Not protocol specified | 5 |
| Overall Study | Progression/relapse | 42 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Gemcitabine and Paclitaxel |
|---|---|
| Age Continuous | 63.1 years |
| Disease Status Newly Diagnosed | 5 participants |
| Disease Status Not Reported | 1 participants |
| Disease Status Persistent | 7 participants |
| Disease Status Recurrent | 50 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants |
| Performance Status 0 | 24 participants |
| Performance Status 1 | 39 participants |
| Primary Site Hypopharynx | 2 participants |
| Primary Site Larynx | 16 participants |
| Primary Site Lip/Oral Cavity | 20 participants |
| Primary Site Nasopharynx | 4 participants |
| Primary Site Oropharynx | 13 participants |
| Primary Site Other/Unknown | 5 participants |
| Primary Site Paranasal Sinuses | 3 participants |
| Primary Site Salivary glands | 0 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 50 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 54 / 63 |
| serious Total, serious adverse events | 0 / 63 |
Outcome results
Primary
Overall Survival
Measured from time of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Time frame: 0 - 3 years
Population: All eligible patients who started treatment were included in this measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemcitabine and Paclitaxel | Overall Survival | 8 months |
Secondary
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug
Adverse Events (AEs) are reported by the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
Time frame: Patients were assessed for adverse events after the first cycle of treatment and then every three months while on treatment.
Population: Eligible patients who received any treatment were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening) or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Allergic reaction/hypersensitivity | 1 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Anorexia | 1 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Dehydration | 1 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Diarrhea | 2 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Dyspnea (shortness of breath) | 2 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Fatigue (asthenia, lethargy, malaise) | 8 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Febrile neutropenia | 3 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Glucose, serum-high (hyperglycemia) | 1 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Hemoglobin | 2 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Hemorrhage, pulmonary/upper respiratory - Nose | 1 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Hypotension | 1 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Inf (clin/microbio) w/Gr 3-4 neuts - Lung | 1 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Inf w/normal ANC or Gr 1-2 neutrophils - Catheter | 1 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Inf w/normal ANC or Gr 1-2 neutrophils - Lung | 1 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Leukocytes (total WBC) | 2 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Lymphopenia | 3 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Memory impairment | 1 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Mucositis/stomatitis (functional/symp) - Oral cav | 1 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Muscle weakness, not d/t neuropathy - body/general | 1 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Neuropathy: motor | 1 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Neuropathy: sensory | 3 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Neutrophils/granulocytes (ANC/AGC) | 7 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Pain - Bone | 1 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Pain-Other (Specify) | 1 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Platelets | 2 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Pneumonitis/pulmonary infiltrates | 1 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Rash/desquamation | 1 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Rash: acne/acneiform | 1 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Sodium, serum-low (hyponatremia) | 3 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Thrombosis/thrombus/embolism | 1 Participants with a given type of AE |
| Gemcitabine and Paclitaxel | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Vomiting | 1 Participants with a given type of AE |
Secondary
Progression-free Survival
Measured from date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact.
Time frame: 0 - 3 years
Population: All eligible patients who started treatment were included in this measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemcitabine and Paclitaxel | Progression-free Survival | 4 months |
Secondary
Response
Complete Response (CR) is complete disappearance of all measurable and non-measurable disease. No new lesions. No disease related symptoms. Normalization of markers and other normal lab values. Partial Response (PR) is greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. Confirmation of CR or PR means a repeat scan at least 4 weeks apart documented before progression or symptomatic deterioration.
Time frame: 9 weeks - 3 years
Population: All eligible patients with measurable disease who started treatment were included in response measures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gemcitabine and Paclitaxel | Response | Complete Response | 1 participants |
| Gemcitabine and Paclitaxel | Response | Partial Response | 6 participants |
| Gemcitabine and Paclitaxel | Response | Unconfirmed Complete Response | 1 participants |
| Gemcitabine and Paclitaxel | Response | Unconfirmed Partial Response | 8 participants |
| Gemcitabine and Paclitaxel | Response | Stable/No Response | 11 participants |
| Gemcitabine and Paclitaxel | Response | Increasing Disease | 21 participants |
| Gemcitabine and Paclitaxel | Response | Assessment Inadequate | 9 participants |