Recurrent Cervical Cancer, Stage IIIA Cervical Cancer, Stage IIIB Cervical Cancer, Stage IVA Cervical Cancer, Stage IVB Cervical Cancer
Conditions
Brief summary
This phase II trial studies how well eribulin mesylate works in treating patients with advanced or recurrent cervical cancer. Drugs used in chemotherapy, such as eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing
Detailed description
PRIMARY OBJECTIVES: I. To evaluate the activity of eribulin (eribulin mesylate) in the management of advanced or recurrent cervical cancer (progression-free survival \[PFS\]. SECONDARY OBJECTIVES: I. To describe the toxicity profile of eribulin in patients with advanced or recurrent cervical cancer. II. To estimate the survival of patients with advanced or recurrent cervical cancer treated with eribulin. III. To evaluate potential correlative studies as predictive or prognostic makers in this patient population (glucose-regulated protein 78 \[GRP78\] levels in tissue and blood, tumor protein p53 \[p53\] expression, apoptosis with terminal deoxynucleotidyl transferase dUTP nick end labeling \[TUNEL\] assay, apoptosis-related proteins B-cell lymphoma 2 \[Bcl-2\] and Bcl2-associated X protein \[Bax\] using immunohistochemistry \[IHC\], proliferation with Ki-67 IHC, and expression levels of microtubule-associated variables, including tau protein, total alpha- and beta-tubulin, and classes II-IV beta-tubulin isotopes with IHC. OUTLINE: Patients receive eribulin mesylate 1.4 mg/m2 intravenously (IV) bolus over 2-5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years.
Interventions
DRUGeribulin mesylate
Given IV
Sponsors
National Cancer Institute (NCI)
University of Southern California
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis of invasive cervical cancer * Measurable disease * 0-1 prior chemotherapy regimens for recurrent or advanced disease; platinum based chemotherapy administered as a radiation sensitizer agent is allowed and does not count as prior therapy * Absolute granulocyte count (AGC) \>= 1,500 * Platelet \>= 100,000 * Serum creatinine \< 2.0 mg/dl * Bilirubin =\< 1.5 times the upper limit of the normal range (ULN) * Alkaline phosphatase =\< 3 x ULN (in the case of liver metastases, =\< 5 x ULN) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN (in the case of liver metastases, =\< 5 x ULN) * Peripheral neuropathy grade 0-2 * Recovery of all chemotherapy or radiation-related toxicities to grade =\< 1, except for alopecia and peripheral neuropathy * Performance status 0-2 * Signed informed consent
Exclusion criteria
* Prior treatment with eribulin * Chemotherapy, radiation, or biological or targeted therapy within 3 weeks * Hormonal therapy within 1 week * Any investigational drug within 4 weeks * Known brain metastases, unless previously treated and asymptomatic for 3 months and not progressive in size or number for 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | From the first day of treatment to the first observation of disease progression or death due to any cause, assessed at 6 months | Progression-free survival measures the length of time a patient with cancer does not experience disease progression or death. It is defined as the time from first day of treatment to the first observation of disease progression or death due to any cause. If a patient has not progressed or died, progression-free survival is censored at the time of last follow-up. |
| Number of Participants With Serious Adverse Events (SAEs) | At study drug administration until 30 days following the last dose. Assessed up to 2 years. | Safety evaluation according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.3 was used to grade all SAEs. Grade 3+ hematologic and non-hematologic toxicities are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response (BOR) | Every 6 weeks from start of treatment until occurrence of progressive disease, assessed up to 4 years. | BOR is defined as the best response recorded from the start of treatment until disease progression/recurrence, evaluated according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 for target lesions and assessed by MRI: Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = at least a 30% decrease in the sum of the diameters of the target lesions compared to the baseline; Stable Disease = Neither enough shrinkage for PR nor enough growth for PD; Progressive Disease = at least a 20% increase in the sum of the diameters of the target lesions from the smallest measurement recorded, with an absolute increase of at least 5 mm, or the appearance of one or more new lesions. |
| Overall Survival (OS) | From first day of treatment to time of death due to any cause, assessed up to 2 years | Overall survival is defined as the time from first day of treatment to time of death due to any cause. If a patient is still alive, survival time is censored at the time of last follow-up. |
Countries
United States
Participant flow
Recruitment details
The study was opened to accrual in August 2012 and closed in April 2018. All patients were seen and treated at USC Norris Comprehensive Cancer Center and/or at Los Angeles County + University of Southern California Medical Center.
Pre-assignment details
The study has no pre-assignment criteria.
Participants by arm
| Arm | Count |
|---|---|
| Eribulin Mesylate Eribulin mesylate 1.4 mg/m2 IV bolus over 2-5 minutes on days 1 and 8 every 21 days in the absence of disease progression or unacceptable toxicity.
eribulin mesylate: Given IV | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Eribulin Mesylate |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants |
| Disease Status Advanced | 11 Participants |
| Disease Status Recurrent | 21 Participants |
| Disease Type Adenocarcinoma | 8 Participants |
| Disease Type Adenosquamous Carcinoma | 1 Participants |
| Disease Type Small Cell Carcinoma | 1 Participants |
| Disease Type Squamous Cell Carcinoma | 22 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Patient Received Prior Chemotherapy No | 3 Participants |
| Patient Received Prior Chemotherapy Yes | 29 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 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 | 5 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Received Prior Paclitaxel (PTX) No | 18 Participants |
| Received Prior Paclitaxel (PTX) Yes | 14 Participants |
| Received Prior Radiation Therapy No | 4 Participants |
| Received Prior Radiation Therapy Yes | 28 Participants |
| Received Prior Regimens Carboplatin + Paclitaxel | 2 Participants |
| Received Prior Regimens Cisplatin + Gemcitabine | 12 Participants |
| Received Prior Regimens Cisplatin + Paclitaxel + Bevacizumab | 12 Participants |
| Received Prior Regimens Cisplatin with/without Premetrexed or Capecitabine only | 3 Participants |
| Received Prior Regimens No Prior Regimen | 3 Participants |
| Region of Enrollment United States | 32 participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 32 |
| other Total, other adverse events | 32 / 32 |
| serious Total, serious adverse events | 25 / 32 |
Outcome results
Primary
Number of Participants With Serious Adverse Events (SAEs)
Safety evaluation according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.3 was used to grade all SAEs. Grade 3+ hematologic and non-hematologic toxicities are reported.
Time frame: At study drug administration until 30 days following the last dose. Assessed up to 2 years.
Population: All patients who were enrolled and treated with at least 1 dose of the study drug were assessed for safety.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eribulin Mesylate | Number of Participants With Serious Adverse Events (SAEs) | 25 Participants |
Primary
Progression-free Survival
Progression-free survival measures the length of time a patient with cancer does not experience disease progression or death. It is defined as the time from first day of treatment to the first observation of disease progression or death due to any cause. If a patient has not progressed or died, progression-free survival is censored at the time of last follow-up.
Time frame: From the first day of treatment to the first observation of disease progression or death due to any cause, assessed at 6 months
Population: All participants are included
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eribulin Mesylate | Progression-free Survival | 2.5 Months |
Secondary
Best Overall Response (BOR)
BOR is defined as the best response recorded from the start of treatment until disease progression/recurrence, evaluated according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 for target lesions and assessed by MRI: Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = at least a 30% decrease in the sum of the diameters of the target lesions compared to the baseline; Stable Disease = Neither enough shrinkage for PR nor enough growth for PD; Progressive Disease = at least a 20% increase in the sum of the diameters of the target lesions from the smallest measurement recorded, with an absolute increase of at least 5 mm, or the appearance of one or more new lesions.
Time frame: Every 6 weeks from start of treatment until occurrence of progressive disease, assessed up to 4 years.
Population: All patients who received at least 1 cycle of treatment are included. 2 patients were excluded due to not being evaluated.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Eribulin Mesylate | Best Overall Response (BOR) | Complete Response | 1 Participants |
| Eribulin Mesylate | Best Overall Response (BOR) | Partial Response | 5 Participants |
| Eribulin Mesylate | Best Overall Response (BOR) | Stable Disease | 13 Participants |
| Eribulin Mesylate | Best Overall Response (BOR) | Progressive Disease | 11 Participants |
Secondary
Overall Survival (OS)
Overall survival is defined as the time from first day of treatment to time of death due to any cause. If a patient is still alive, survival time is censored at the time of last follow-up.
Time frame: From first day of treatment to time of death due to any cause, assessed up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eribulin Mesylate | Overall Survival (OS) | 6.5 Months |