Salivary Cancer
Conditions
Brief summary
This study will test any good and bad effects of the study drug called enzalutamide. Enzalutamide could shrink the cancer but it could also cause side effects. Researchers hope to learn if the study drug will shrink the cancer by at least 30% compared to its present size, in at least 1 out of 5 patients. Enzalutamide is not FDA approved to treat salivary gland cancer, but it has already been FDA-approved to treat other cancers.
Detailed description
This single arm Phase II trial will assess the best overall response associated with enzalutamide in patients with AR-positive salivary cancers. Given that this will be one of the first prospective studies ever conducted for AR-positive salivary cancers, and there are currently no standard therapies known to be effective for this disease, the investigators will adopt a best overall response (BOR) of 5% as the null hypothesis and BOR of 20 % as the alternative hypothesis. In addition to response, this study will also evaluate the progression-free survival (PFS), overall survival (OS), adverse events, and will also try to identify molecular predictors of response by examining genomic and transcriptional elements of androgen receptor biology. The primary and secondary objectives of the study: Primary objective To evaluate the rate of best overall response associated with enzalutamide in patients with AR-positive salivary cancers Secondary objectives 1. To evaluate the progression-free survival (PFS) of AR-positive salivary cancer patients treated with enzalutamide 2. To evaluate the overall survival (OS) of AR-positive salivary cancer patients treated with enzalutamide 3. To evaluate the safety/tolerability of enzalutamide for patients with AR-positive salivary cancer Patients are followed up to 3 years after study enrollment.
Interventions
oral
Sponsors
Study design
Eligibility
Inclusion criteria
1. Documentation of Disease - Histologic Documentation: Histologically proven diagnosis of salivary cancer by central pathology review. Receptor status: AR expression detected by immunohistochemistry by central review. 2. Disease status - Measurable disease as defined in the protocol. Locally advanced/unresectable (as determined by local surgeon) OR metastatic disease. 3. Prior Treatment * Any number of prior lines of therapy * No treatment with biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy, or radiation ≤ 28 days before study registration. No treatment with nitrosourea or mitomycin ≤ 42 days before study registration * No prior therapy with enzalutamide (previous chemotherapy and/or other AR-targeted approaches is allowed). 4. Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. A female of childbearing potent is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (ie, has had menses at any time in the preceding 12 consecutive months). For women of childbearing potential only, a negative pregnancy test done ≤ 5 days prior to registration is required. 5. Age ≥ 18 years 6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 7. No History of the following: * prior brain metastases * leptomeningeal disease * seizures * class 3 or 4 congestive heart failure * uncontrolled hypertension (systolic BP \> 170 mmHg or diastolic BP \> 105 mmHg) * major surgery ≤ 4 weeks of registration 8. Required Initial Laboratory Values: * Absolute Neutrophil Count (ANC) ≥ 1,500/mm3 * Platelet Count ≥ 100,000/mm3 * Creatinine ≤ 1.5 x ULN Upper Limit of Normal (ULN) OR * Calculated Creatinine Clearance ≥ 30 mL/min * Total Bilirubin ≤ 1.5 x ULN * AST/ALT ≤ 3.0 x ULN 9. Concomitant medications- Chronic concomitant treatment with strong CYP2C8 inhibitors is not allowed. Patients must discontinue the drug ≥ 14 days prior to registration. Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug ≥ 14 days prior to registration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response Rate | Up to 32 weeks | The best overall response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Up to 32 months post study enrollment | Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
| Number of Patients Experiencing at Least One Grade 3+ Adverse Event Using CTCAE Version 4.0 | 30 days post-treatment, up to 32 months | The number of patients experiencing at least one grade 3+ adverse event using CTCAE version 4.0 is summarized below. |
Countries
United States
Contacts
Memorial Sloan Kettering Cancer Center
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Enzalutamide Patients receive 160 mg enzalutamide orally once daily (1 cycle=28 days). Patients will remain on therapy until progression of disease or development of unacceptable toxicities or patient or physician withdrawal. Patients will undergo radiographic imaging every 2 months while on study treatment in order to determine response. | 46 |
| Total | 46 |
Baseline characteristics
| Characteristic | Enzalutamide |
|---|---|
| Age, Continuous | 67.1 years STANDARD_DEVIATION 10.8 |
| ECOG Performance Status 0 | 25 Participants |
| ECOG Performance Status 1 | 21 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 39 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 27 / 46 |
| other Total, other adverse events | 44 / 46 |
| serious Total, serious adverse events | 15 / 46 |
Outcome results
Best Overall Response Rate
The best overall response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients.
Time frame: Up to 32 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enzalutamide | Best Overall Response Rate | 4.3 percentage of patients |
Number of Patients Experiencing at Least One Grade 3+ Adverse Event Using CTCAE Version 4.0
The number of patients experiencing at least one grade 3+ adverse event using CTCAE version 4.0 is summarized below.
Time frame: 30 days post-treatment, up to 32 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Enzalutamide | Number of Patients Experiencing at Least One Grade 3+ Adverse Event Using CTCAE Version 4.0 | 22 Participants |
Progression-free Survival
Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: Up to 32 months post study enrollment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enzalutamide | Progression-free Survival | 5.6 months |