Head and Neck Cancer
Conditions
Keywords
metastatic squamous neck cancer with occult primary squamous cell carcinoma, recurrent metastatic squamous neck cancer with occult primary, recurrent squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the larynx, recurrent squamous cell carcinoma of the lip and oral cavity, recurrent squamous cell carcinoma of the oropharynx, recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity, stage IV squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity, untreated metastatic squamous neck cancer with occult primary, salivary gland squamous cell carcinoma
Brief summary
RATIONALE: Drugs used in chemotherapy, such as E7389, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase II trial is studying how well E7389 works in treating patients with metastatic or recurrent head and neck cancer.
Detailed description
OBJECTIVES: * Evaluate the response probability (confirmed, complete, and partial responses) in patients with metastatic or recurrent squamous cell carcinoma of the head and neck treated with E7389. * Estimate progression-free and overall survival probability in these patients. * Evaluate the qualitative and quantitative toxicities of this treatment regimen. OUTLINE: This is a multicenter study. Patients receive E7389 IV on days 1 and 8. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression. After completion of study treatment, patients are followed periodically for up to 3 years. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Interventions
DRUGeribulin mesylate
1.4 mg/m2 by IV bolus on Days 1 and 8 of an every 21-day cycle.
Sponsors
National Cancer Institute (NCI)
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) * Disease is either metastatic at diagnosis or has persisted, metastasized, or recurred after definitive surgery and/or radiotherapy * Not amenable to surgical resection for salvage therapy * No newly diagnosed nonmetastatic disease * No salivary or nasopharyngeal primary disease * Patients who have failed primary surgery alone, and who have disease that is salvageable by radiation or chemoradiation, are not eligible * Measurable disease * Measurable disease within a previous radiotherapy port must demonstrate clearly progressive disease * No active or prior CNS metastasis PATIENT CHARACTERISTICS: * Zubrod performance status 0-1 * Absolute granulocyte count ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Bilirubin ≤ 2 times upper limit of normal (ULN) * SGOT and SGPT ≤ 2 times ULN * Creatinine ≤ 2 times ULN * Not pregnant or nursing * Fertile patients must use effective contraception * No known HIV positivity * No prior malignancies except for the following: * Adequately treated basal cell or squamous cell skin cancer * In situ cervical cancer * Adequately treated stage I or II cancer currently in complete remission * Any other cancer for which the patient has been disease free for ≥ 5 years PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior chemotherapy for recurrent or newly diagnosed metastatic disease * At least 6 months since prior induction or adjuvant chemotherapy for patients who relapsed after receiving this therapy * No more than 1 prior induction or adjuvant regimen (may have included a taxane) * More than 2 weeks since prior biologic therapy (i.e., epidermal growth factor inhibitors and vascular endothelial growth factor inhibitors) * More than 28 days since prior radiotherapy and recovered * More than 28 days since prior surgery and recovered * No other concurrent therapy (i.e., radiotherapy, chemotherapy, immunotherapy, biologic therapy, or gene therapy) for SCCHN * No concurrent combination antiretroviral therapy for HIV-positive patients * No concurrent prophylactic colony-stimulating factors during course 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Probability (Confirmed Complete and Partial Responses) | Every 6 weeks until progression of disease up to a maximum of 3 years after registration | Response was defined per RECIST. Complete response (CR) was defined as complete disappearance of all baseline measurable and non-measurable disease with no new lesions. Partial response (PR) was defined as at least 30% decrease under baseline of the sum of longest diameters of all target measurable lesions with no unequivocal progression of non-measurable disease and no new lesions. A CR or PR must be confirmed by a second determination at least 4 weeks apart. All disease must have been assessed using the same technique as baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | Every 6 weeks until progression of disease up to a maximum of 3 years after registration. | Progression-free survival was defined as the time from date of registration to the date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free were censored at date of last contact. |
| Overall Survival | Every 3 months for first year, then every six months thereafter up to a maximum of 3 years from registration. | Overall survival was defined as the time from the date of registration to the date of death due to any cause. Patients last known to be alive are censored at date of last contact. |
| Participants With a Given Type of AE | Every 3 weeks while on protocol therapy, up to 3 years. | The NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0 was utilized. |
Countries
United States
Participant flow
Recruitment details
From June 2006 to December, 2007 a total of 42 patients were enrolled from SWOG institutions
Pre-assignment details
2 patients are not eligible before assignment.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (E7389 IV) Patients receive E7389 IV on days 1 and 8 of an every 21-day cycle. | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Death | 2 |
| Overall Study | Lack of Efficacy | 32 |
| Overall Study | not protocol specified | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment (E7389 IV) |
|---|---|
| Age, Continuous | 61 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 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 | 1 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 36 / 40 |
| serious Total, serious adverse events | 5 / 40 |
Outcome results
Primary
Response Probability (Confirmed Complete and Partial Responses)
Response was defined per RECIST. Complete response (CR) was defined as complete disappearance of all baseline measurable and non-measurable disease with no new lesions. Partial response (PR) was defined as at least 30% decrease under baseline of the sum of longest diameters of all target measurable lesions with no unequivocal progression of non-measurable disease and no new lesions. A CR or PR must be confirmed by a second determination at least 4 weeks apart. All disease must have been assessed using the same technique as baseline.
Time frame: Every 6 weeks until progression of disease up to a maximum of 3 years after registration
Population: Only eligible patients were included in the analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (E7389 IV) | Response Probability (Confirmed Complete and Partial Responses) | Complete Response | 0 participants |
| Treatment (E7389 IV) | Response Probability (Confirmed Complete and Partial Responses) | Partial Response | 2 participants |
| Treatment (E7389 IV) | Response Probability (Confirmed Complete and Partial Responses) | No Response | 38 participants |
Comparison: Null hypothesis: response probability \< 5%; alternative hypothesis: response probability \> 20%. A two-stage design was used. If no responses among the first 20 patients, the study would be terminated with the conclusion that E7389 is inactive. However, if at least one response was seen then an additional 20 patients would be accrued. Five or more responses out of 40 would be considered evidence that E7389 warranted further study. This design had a significance level of 5% and a power of 92%.95% CI: [0.01, 0.17]two-stage binomial
Secondary
Overall Survival
Overall survival was defined as the time from the date of registration to the date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Time frame: Every 3 months for first year, then every six months thereafter up to a maximum of 3 years from registration.
Population: Only eligible patients were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (E7389 IV) | Overall Survival | 7 months |
Secondary
Participants With a Given Type of AE
The NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0 was utilized.
Time frame: Every 3 weeks while on protocol therapy, up to 3 years.
Population: All eligible patients who started protocol treatment are included in analysis of toxicity
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (E7389 IV) | Participants With a Given Type of AE | Hemoglobin | 1 participants |
| Treatment (E7389 IV) | Participants With a Given Type of AE | Dehydration | 1 participants |
| Treatment (E7389 IV) | Participants With a Given Type of AE | Diarrhea | 2 participants |
| Treatment (E7389 IV) | Participants With a Given Type of AE | Dry mouth/salivary gland (xerostomia) | 1 participants |
| Treatment (E7389 IV) | Participants With a Given Type of AE | Dyspnea (shortness of breath) | 2 participants |
| Treatment (E7389 IV) | Participants With a Given Type of AE | Fatigue (asthenia, lethargy, malaise) | 2 participants |
| Treatment (E7389 IV) | Participants With a Given Type of AE | Glucose, serum-high (hyperglycemia) | 1 participants |
| Treatment (E7389 IV) | Participants With a Given Type of AE | Hemorrhage - Bronchopulmonary NOS | 1 participants |
| Treatment (E7389 IV) | Participants With a Given Type of AE | Infection w/ Grade 3/4 ANC - Skin (cellulitis) | 1 participants |
| Treatment (E7389 IV) | Participants With a Given Type of AE | Infection w unk ANC - gums (gingivitis) | 1 participants |
| Treatment (E7389 IV) | Participants With a Given Type of AE | Leukocytes (total WBC) | 5 participants |
| Treatment (E7389 IV) | Participants With a Given Type of AE | Lymphopenia | 6 participants |
| Treatment (E7389 IV) | Participants With a Given Type of AE | Mucositis - gums (gingivitis) | 1 participants |
| Treatment (E7389 IV) | Participants With a Given Type of AE | Neuropathy: sensory | 1 participants |
| Treatment (E7389 IV) | Participants With a Given Type of AE | Neutrophils/granulocytes (ANC/AGC) | 4 participants |
| Treatment (E7389 IV) | Participants With a Given Type of AE | Pneumonitis/pulmonary infiltrates | 1 participants |
| Treatment (E7389 IV) | Participants With a Given Type of AE | Potassium, serum-low (hypokalemia) | 1 participants |
| Treatment (E7389 IV) | Participants With a Given Type of AE | Sodium, serum-low (hyponatremia) | 2 participants |
Secondary
Progression-Free Survival
Progression-free survival was defined as the time from date of registration to the date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free were censored at date of last contact.
Time frame: Every 6 weeks until progression of disease up to a maximum of 3 years after registration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (E7389 IV) | Progression-Free Survival | 3 months |