Ovarian Cancer
Conditions
Keywords
recurrent ovarian epithelial cancer
Brief summary
RATIONALE: Estrogen can cause the growth of ovarian epithelial cancer cells. Hormone therapy using fulvestrant may fight ovarian cancer by blocking the use of estrogen by the tumor cells. PURPOSE: This phase II trial is studying how well fulvestrant works in treating patients with recurrent ovarian epithelial cancer.
Detailed description
OBJECTIVES: Primary * To determine the 90-day clinical benefit (defined as the sum of complete responses, partial responses, and stable disease) in patients with recurrent ovarian epithelial cancer treated with single agent fulvestrant. Secondary * To establish the time to termination of treatment (due to all causes including progression and intolerance) for patients treated with this drug. * To describe the toxicities observed in patients treated with this drug. * To evaluate the quality of life of patients treated with this drug. * To determine the effect that prolonged estrogen receptor antagonism has on markers of bone mineral turnover. OUTLINE: Patients receive fulvestrant intramuscularly on days 1 and 15 of course 1 and then on day 1 of all subsequent courses. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients in continued response at the end of 1 year may continue treatment at the discretion of the treating physician. Urinary N-telopeptide and serum skeletal-specific alkaline phosphatase are assessed at baseline and at 1, 3, and 6 months during study to determine the influence of estrogen blockade on bone mineral turnover. Quality of life is assessed at baseline and every 3 months during treatment, and at the end of treatment using The Functional Assessment of Cancer Therapy - Ovarian (FACT-O) cancer questionnaire. After completion of study treatment, patients are followed at approximately 30 days.
Interventions
DRUGFulvestrant
Fulvestrant, 500 milligrams (mg) intramuscularly (IM) on Day 1, 250 mg IM on Day 15, and 250 mg IM on Day 29 and every 28 days thereafter until either intolerance or disease progression.
Sponsors
Masonic Cancer Center, University of Minnesota
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 ovarian epithelial carcinoma * Recurrent or persistent disease * Must have received greater than or equal to (≥) 2 prior cytotoxic chemotherapy regimens, including ≥ 1 platinum-containing regimen * Disease not amenable to curative treatment with surgery and/or radiotherapy * Must have measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) and/or a serum cancer antigen 125 (CA-125) level that is rising and meets 1 of the following criteria: * Serum CA-125 level greater than (\>) upper limit of normal (typically 35 μ/mL) on two evaluations at least 2 weeks apart * Serum CA-125 level less than (\<) 35 μ/mL but has risen progressively \> 200% over successive specimens ≥ 2 weeks apart * Estrogen receptor-positive tumor * Gynecologic Oncology Group (GOG) performance status 0-3 * Platelet count ≥ 50 x 10\^9/Liter * Serum creatinine less than or equal to (≤) 2.5 mg/deciliter * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * Serum glutamic oxaloacetic transaminase (SGOT) ≤ 3 times upper limit of normal (ULN) * alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases) * Alkaline phosphatase ≤ 3 times ULN * Prothrombin time-International Normalized Ratio (INR) ≤ 1.6 * Not pregnant or nursing * Negative pregnancy test * Must be sterile or fertile patients must use effective contraception (i.e., double method including ≥ 1 barrier, injectable, implantable, condoms plus spermicide) * Prior malignancy allowed provided the patient has been disease-free for ≥ 5 years * Patients with previously diagnosed basal cell skin cancer are eligible immediately after completing therapy * No history of bleeding (i.e., disseminated intravascular coagulation or clotting factor deficiency) * No documented sensitivity to active or inactive excipients of fulvestrant (i.e., castor oil or mannitol) * Recovered from the effects of prior surgery, radiotherapy, and/or chemoradiotherapy * At least 3 weeks since prior chemotherapy * At least 3 weeks since prior complete radiotherapy regimen alone or chemoradiotherapy * An incomplete radiotherapy regimen (\< 500 Gray) is allowed within the 3-week time frame
Exclusion criteria
* Concurrent hormone replacement therapy * Prior long-term anticoagulation therapy other than anti-platelet therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patients' Overall 90-Day Clinical Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) | Day 90 | Best response recorded from the start of treatment until Day 90. Defined by the sum of the Complete Responses (CR), Partial Responses (PR) and Stable Disease (SD) in patients treated with fulvestrant. CR=disappearance of all lesions, PR=\>or =30% decrease in sum of all target lesions, Progressive Disease (PD) =\>or=20% increase in sum of all target or any new lesions, SD=not CR, PR or PD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patients' Overall 90-Day Clinical Response as Measured by Modified Response Evaluation Criteria in Solid Tumors (Rustin) | Day 90 | Defined by the sum of Complete Responses (CR), Partial Responses (PR) and Stable Disease (SD) in patients treated with fulvestrant. CR=normalization of serum CA-125 level from 2 initially elevated samples, PR=\>or=50% decrease in serum CA-125 level from 2 initially elevated samples, Progressive Disease (PD)=CA-125 two times the upper limit of normal on 2 occasions (if previously normalized) OR CA-125 two times nadir (lowest value) on 2 occasions if elevated at initiation of treatment, SD=not CR, PR or PD. |
| Median Number of Days to Treatment Termination | Up to 373 Days | Time is determined from first dose to termination due to all causes. |
| Mean Scores - Quality of Life Assessment | Baseline, 3 Months Post Treatment, 6 Months Post Treatment | Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O)Version 1/23/07 - This is a relative quality of life assessment; 100 = Best, 0 = Worst. It was developed and validated with cancer patients and includes physical well being, social well being, emotional well being and relationship with doctor subscales and can be summed into one total quality of life score. It is a standardized scale which collects data (scores 1-4) from 47 questions. Answers are transformed into a number between 0-100. Mean was calculated by adding up the values of the scores and dividing by the number of scores. |
| Serum Skeletal-Specific Alkaline Phosphatase Concentration | Baseline, 1 Month, 3 Months, 6 Months | Median Bone mineral results - assessed by serum skeletal-specific alkaline phosphatase laboratory results collected from patients in study. |
| Urine N-telopeptide Concentration | Baseline, 1 Month, 3 Months, 6 Months | Median bone mineral results - assessed by serial urine N-telopeptide laboratory results collected from patients. |
Countries
United States
Participant flow
Pre-assignment details
3 additional patients were enrolled, but were never treated.
Participants by arm
| Arm | Count |
|---|---|
| Fulvestrant Treatment Patients who met Inclusion Criteria and received at least 1 dose of study drug (Fulvestrant 500 mg Day 1; 250 mg Day 1, 29 and every 28 days thereafter) | 26 |
| Total | 26 |
Baseline characteristics
| Characteristic | Fulvestrant Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 26 |
| serious Total, serious adverse events | 10 / 26 |
Outcome results
Primary
Patients' Overall 90-Day Clinical Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST)
Best response recorded from the start of treatment until Day 90. Defined by the sum of the Complete Responses (CR), Partial Responses (PR) and Stable Disease (SD) in patients treated with fulvestrant. CR=disappearance of all lesions, PR=\>or =30% decrease in sum of all target lesions, Progressive Disease (PD) =\>or=20% increase in sum of all target or any new lesions, SD=not CR, PR or PD.
Time frame: Day 90
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fulvestrant Treatment | Patients' Overall 90-Day Clinical Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) | Progressive Disease (>=20% increase/new lesions) | 18 Participants |
| Fulvestrant Treatment | Patients' Overall 90-Day Clinical Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) | Stable Disease | 8 Participants |
Secondary
Mean Scores - Quality of Life Assessment
Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O)Version 1/23/07 - This is a relative quality of life assessment; 100 = Best, 0 = Worst. It was developed and validated with cancer patients and includes physical well being, social well being, emotional well being and relationship with doctor subscales and can be summed into one total quality of life score. It is a standardized scale which collects data (scores 1-4) from 47 questions. Answers are transformed into a number between 0-100. Mean was calculated by adding up the values of the scores and dividing by the number of scores.
Time frame: Baseline, 3 Months Post Treatment, 6 Months Post Treatment
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Fulvestrant Treatment | Mean Scores - Quality of Life Assessment | Baseline (rounded to nearest whole number) | 87 Scores on a Scale |
| Fulvestrant Treatment | Mean Scores - Quality of Life Assessment | 3 Months (rounded to nearest whole number) | 84 Scores on a Scale |
| Fulvestrant Treatment | Mean Scores - Quality of Life Assessment | 6 Months (rounded to nearest whole number) | 81 Scores on a Scale |
Secondary
Median Number of Days to Treatment Termination
Time is determined from first dose to termination due to all causes.
Time frame: Up to 373 Days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant Treatment | Median Number of Days to Treatment Termination | 62 Days |
Secondary
Patients' Overall 90-Day Clinical Response as Measured by Modified Response Evaluation Criteria in Solid Tumors (Rustin)
Defined by the sum of Complete Responses (CR), Partial Responses (PR) and Stable Disease (SD) in patients treated with fulvestrant. CR=normalization of serum CA-125 level from 2 initially elevated samples, PR=\>or=50% decrease in serum CA-125 level from 2 initially elevated samples, Progressive Disease (PD)=CA-125 two times the upper limit of normal on 2 occasions (if previously normalized) OR CA-125 two times nadir (lowest value) on 2 occasions if elevated at initiation of treatment, SD=not CR, PR or PD.
Time frame: Day 90
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fulvestrant Treatment | Patients' Overall 90-Day Clinical Response as Measured by Modified Response Evaluation Criteria in Solid Tumors (Rustin) | Stable Disease | 13 Participants |
| Fulvestrant Treatment | Patients' Overall 90-Day Clinical Response as Measured by Modified Response Evaluation Criteria in Solid Tumors (Rustin) | Progressive Disease (>= 20% increase/new lesions) | 13 Participants |
Secondary
Serum Skeletal-Specific Alkaline Phosphatase Concentration
Median Bone mineral results - assessed by serum skeletal-specific alkaline phosphatase laboratory results collected from patients in study.
Time frame: Baseline, 1 Month, 3 Months, 6 Months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Fulvestrant Treatment | Serum Skeletal-Specific Alkaline Phosphatase Concentration | Alkaline Phosphase levels - 6 Months | 16.2 Units/Liter |
| Fulvestrant Treatment | Serum Skeletal-Specific Alkaline Phosphatase Concentration | Alkaline Phosphatase levels - Baseline | 14.0 Units/Liter |
| Fulvestrant Treatment | Serum Skeletal-Specific Alkaline Phosphatase Concentration | Alkaline Phosphatase levels - 1 Month | 16.1 Units/Liter |
| Fulvestrant Treatment | Serum Skeletal-Specific Alkaline Phosphatase Concentration | Alkaline Phosphase levels - 3 Months | 18.5 Units/Liter |
Secondary
Urine N-telopeptide Concentration
Median bone mineral results - assessed by serial urine N-telopeptide laboratory results collected from patients.
Time frame: Baseline, 1 Month, 3 Months, 6 Months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Fulvestrant Treatment | Urine N-telopeptide Concentration | Urinary N-telopeptide level - Baseline | 50 Units of Bone Collagen Equivalents/mmol |
| Fulvestrant Treatment | Urine N-telopeptide Concentration | Urinary N-telopeptide level - 1 Month | 49 Units of Bone Collagen Equivalents/mmol |
| Fulvestrant Treatment | Urine N-telopeptide Concentration | Urinary N-telopeptide level - 3 Months | 43 Units of Bone Collagen Equivalents/mmol |
| Fulvestrant Treatment | Urine N-telopeptide Concentration | Urinary N-telopeptide level - 6 Months | 46 Units of Bone Collagen Equivalents/mmol |