Recurrent Uterine Corpus Carcinoma, Stage III Uterine Corpus Cancer AJCC v7, Stage IV Uterine Corpus Cancer AJCC v7
Conditions
Brief summary
This phase II trial is studying fulvestrant to see how well it works in treating patients with recurrent, persistent, or metastatic endometrial cancer. Estrogen can stimulate the growth of cancer cells. Hormone therapy using fulvestrant may fight cancer by blocking the uptake of estrogen by the tumor cells.
Detailed description
PRIMARY OBJECTIVES: I. Compare the probability of clinical response in estrogen receptor (ER)-positive vs ER-negative patients with recurrent, persistent, or metastatic endometrial cancer treated with fulvestrant. II. Compare the relationship between response rate and intensity of receptor expression in patients treated with this drug. III. Determine the frequency and intensity of toxicity of this drug in these patients. OUTLINE: Patients receive fulvestrant intramuscularly on day 1. Treatment repeats every 28 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Interventions
DRUGFulvestrant
Given intramuscularly
Sponsors
National Cancer Institute (NCI)
Gynecologic Oncology Group
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
Criteria: * Histologically confirmed recurrent, persistent, or metastatic endometrial cancer that is not curable with surgery or radiotherapy * Estrogen receptor (ER) and progesterone receptor status known by immunohistochemistry * ER positive or negative allowed * Measurable disease: * At least 1 target lesion not within a previously irradiated field OR irradiated target lesion with clear disease progression * At least 20 mm by conventional techniques, including palpation, x-ray, CT scan, MRI, OR at least 10 mm by spiral CT scan * Performance status: * GOG 0-1 * Hematopoietic: * Absolute neutrophil count \>= 1,500/mm\^3 * Platelet count \>= 100,000/mm\^3 * No prior bleeding diathesis (disseminated intravascular coagulation, clotting factor deficiency, or requirement for anticoagulants) * Hepatic: * Bilirubin =\< 1.5 times upper limit of normal (ULN) * SGOT =\< 3 times ULN * Alkaline phosphatase =\< 3 times ULN * Renal: * Creatinine =\< 2 mg/dL * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No hypersensitivity to castor oil * No other concurrent malignancy except nonmelanoma skin cancer * No other prior malignancy within past 5 years * No prior chemotherapy for persistent, recurrent, or metastatic endometrial cancer * No more than 1 prior chemotherapy regimen for newly diagnosed endometrial cancer that has subsequently recurred * At least 3 weeks since prior hormonal therapy and recovered * At least 3 weeks since prior radiotherapy and recovered * At least 3 weeks since prior surgery and recovered
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Evaluated Every 8 Weeks | Response was measured every other cycle (every 8 weeks) until disease progression is documented or adverse events preclude further treatment. | Primary outcome measured according to RECIST v1.0 Best Response: Complete Response (CR) is disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart Disease Progression is at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. Partial Response (PR) is at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of nontarget lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required Stable Disease is any condition not meeting the above criteria. Indeterminate is defined as having no repeat tumor assessments following initiation of study therapy for reasons unrelated to symptoms or signs of disease. |
| Clinical Response by RECIST Criteria of Estrogen Receptor Expression | Every other cycle (every 8 weeks) until disease progression is documented or adverse events preclude further treatment, assessed up to 100 months. | Per response evaluation criteria in Solid Tumors Criteria (RECIST 1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR) \>=30% decrease in the sum of the longest diameter of target lesions. Overall Response = CR+PR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | During study treatment and up to 30 days after stopping study | Adverse events at least possibly related to Fulvestrant using Common Terminology Criteria version 3.0 that were grade 3 or higher with the exception of the reported Grade 5. Grade 5 adverse events were reported regardless of attribution to study treatment. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Estrogen Receptor Negative Estrogen Receptor Negative, Faslodex® 250mg intramuscularly per month, minimum treatment period two cycles until disease progression or adverse effects prohibit further therapy | 23 |
| Estrogen Receptor Positive Estrogen Receptor Postive, Faslodex® 250mg intramuscularly per month, minimum treatment period two cycles until disease progression or adverse effects prohibit further therapy | 30 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Ineligible | 10 | 1 | 2 |
| Overall Study | Patient never treated | 0 | 0 | 1 |
| Overall Study | Refused further treatment | 0 | 2 | 1 |
| Overall Study | Still receiving treatment | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Estrogen Receptor Negative | Estrogen Receptor Positive | Total |
|---|---|---|---|
| Age, Customized | 62.9 years STANDARD_DEVIATION 10.2 | 65.9 years STANDARD_DEVIATION 10.4 | 64.6 years STANDARD_DEVIATION 10.4 |
| Sex: Female, Male Female | 23 Participants | 30 Participants | 53 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 28 / 53 |
| serious Total, serious adverse events | 11 / 53 |
Outcome results
Primary
Clinical Response by RECIST Criteria of Estrogen Receptor Expression
Per response evaluation criteria in Solid Tumors Criteria (RECIST 1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR) \>=30% decrease in the sum of the longest diameter of target lesions. Overall Response = CR+PR
Time frame: Every other cycle (every 8 weeks) until disease progression is documented or adverse events preclude further treatment, assessed up to 100 months.
Population: Total number eligible and treated participants within groups defined by estrogen receptor status
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Estrogen Receptor Negative | Clinical Response by RECIST Criteria of Estrogen Receptor Expression | Partial Response | 0 Participants |
| Estrogen Receptor Negative | Clinical Response by RECIST Criteria of Estrogen Receptor Expression | Increasing Disease | 17 Participants |
| Estrogen Receptor Negative | Clinical Response by RECIST Criteria of Estrogen Receptor Expression | Stable Disease | 4 Participants |
| Estrogen Receptor Negative | Clinical Response by RECIST Criteria of Estrogen Receptor Expression | Not Evaluated | 1 Participants |
| Estrogen Receptor Negative | Clinical Response by RECIST Criteria of Estrogen Receptor Expression | Complete Response | 0 Participants |
| Estrogen Receptor Positive | Clinical Response by RECIST Criteria of Estrogen Receptor Expression | Not Evaluated | 0 Participants |
| Estrogen Receptor Positive | Clinical Response by RECIST Criteria of Estrogen Receptor Expression | Complete Response | 1 Participants |
| Estrogen Receptor Positive | Clinical Response by RECIST Criteria of Estrogen Receptor Expression | Partial Response | 4 Participants |
| Estrogen Receptor Positive | Clinical Response by RECIST Criteria of Estrogen Receptor Expression | Stable Disease | 9 Participants |
| Estrogen Receptor Positive | Clinical Response by RECIST Criteria of Estrogen Receptor Expression | Increasing Disease | 17 Participants |
Primary
Clinical Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Evaluated Every 8 Weeks
Primary outcome measured according to RECIST v1.0 Best Response: Complete Response (CR) is disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart Disease Progression is at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. Partial Response (PR) is at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of nontarget lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required Stable Disease is any condition not meeting the above criteria. Indeterminate is defined as having no repeat tumor assessments following initiation of study therapy for reasons unrelated to symptoms or signs of disease.
Time frame: Response was measured every other cycle (every 8 weeks) until disease progression is documented or adverse events preclude further treatment.
Population: Total number eligible and treated participants within groups defined by estrogen receptor status in metastatic tumor.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Estrogen Receptor Negative | Clinical Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Evaluated Every 8 Weeks | Disease Progression | 18 participants |
| Estrogen Receptor Negative | Clinical Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Evaluated Every 8 Weeks | Stable Disease | 4 participants |
| Estrogen Receptor Negative | Clinical Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Evaluated Every 8 Weeks | Indeterminate | 1 participants |
| Estrogen Receptor Negative | Clinical Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Evaluated Every 8 Weeks | Complete Response | 0 participants |
| Estrogen Receptor Negative | Clinical Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Evaluated Every 8 Weeks | Partial Response | 0 participants |
| Estrogen Receptor Positive | Clinical Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Evaluated Every 8 Weeks | Indeterminate | 0 participants |
| Estrogen Receptor Positive | Clinical Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Evaluated Every 8 Weeks | Partial Response | 4 participants |
| Estrogen Receptor Positive | Clinical Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Evaluated Every 8 Weeks | Stable Disease | 9 participants |
| Estrogen Receptor Positive | Clinical Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Evaluated Every 8 Weeks | Disease Progression | 16 participants |
| Estrogen Receptor Positive | Clinical Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Evaluated Every 8 Weeks | Complete Response | 1 participants |
Secondary
Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug.
Adverse events at least possibly related to Fulvestrant using Common Terminology Criteria version 3.0 that were grade 3 or higher with the exception of the reported Grade 5. Grade 5 adverse events were reported regardless of attribution to study treatment.
Time frame: During study treatment and up to 30 days after stopping study
Population: Eligible and evaluable patients.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Estrogen Receptor Negative | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Gastrointestinal | 1 Participants |
| Estrogen Receptor Negative | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Dyspnea | 1 Participants |
| Estrogen Receptor Negative | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Metabolic | 2 Participants |
| Estrogen Receptor Negative | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Nausea | 3 Participants |
| Estrogen Receptor Negative | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Anorexia | 2 Participants |
| Estrogen Receptor Negative | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Vomiting | 1 Participants |
| Estrogen Receptor Negative | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Pain | 1 Participants |
| Estrogen Receptor Negative | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Anemia | 1 Participants |
| Estrogen Receptor Negative | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Diarrhea | 1 Participants |
| Estrogen Receptor Negative | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Depression | 1 Participants |
| Estrogen Receptor Negative | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Fatigue | 1 Participants |
| Estrogen Receptor Negative | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Thrombosis/embolism, regardless of attribution | 0 Participants |
| Estrogen Receptor Negative | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Neurologic | 2 Participants |
| Estrogen Receptor Positive | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Thrombosis/embolism, regardless of attribution | 3 Participants |
| Estrogen Receptor Positive | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Diarrhea | 0 Participants |
| Estrogen Receptor Positive | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Anemia | 1 Participants |
| Estrogen Receptor Positive | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Fatigue | 0 Participants |
| Estrogen Receptor Positive | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Gastrointestinal | 0 Participants |
| Estrogen Receptor Positive | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Nausea | 0 Participants |
| Estrogen Receptor Positive | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Anorexia | 0 Participants |
| Estrogen Receptor Positive | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Metabolic | 0 Participants |
| Estrogen Receptor Positive | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Neurologic | 0 Participants |
| Estrogen Receptor Positive | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Depression | 0 Participants |
| Estrogen Receptor Positive | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Pain | 0 Participants |
| Estrogen Receptor Positive | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Dyspnea | 0 Participants |
| Estrogen Receptor Positive | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Vomiting | 0 Participants |
| Grade 5 | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Diarrhea | 0 Participants |
| Grade 5 | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Neurologic | 0 Participants |
| Grade 5 | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Anemia | 0 Participants |
| Grade 5 | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Vomiting | 0 Participants |
| Grade 5 | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Depression | 0 Participants |
| Grade 5 | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Thrombosis/embolism, regardless of attribution | 1 Participants |
| Grade 5 | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Nausea | 0 Participants |
| Grade 5 | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Dyspnea | 0 Participants |
| Grade 5 | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Anorexia | 0 Participants |
| Grade 5 | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Gastrointestinal | 0 Participants |
| Grade 5 | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Pain | 0 Participants |
| Grade 5 | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Metabolic | 0 Participants |
| Grade 5 | Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug. | Fatigue | 0 Participants |