Fulvestrant in Treating Patients With Recurrent, Persistent, or Metastatic Endometrial Cancer

• Sponsor: Gynecologic Oncology Group (Other)
• Overall Status: Unknown status
• CT.gov ID: NCT00006903
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 67
• Arm: 1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Uterine Corpus Carcinoma; Stage III Uterine Corpus Cancer AJCC v7; Stage IV Uterine Corpus Cancer AJCC v7	Drug: Fulvestrant	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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.

2. Compare the relationship between response rate and intensity of receptor expression in patients treated with this drug.

3. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 67 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Faslodex ? in Recurrent/Metastatic Endometrial Carcinoma
• Actual Study Start Date: Aug 30, 2004
• Actual Primary Completion Date: Mar 17, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (fulvestrant) 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.	Drug: Fulvestrant; Given intramuscularly; Other Names: Faslodex Faslodex(ICI 182,780) ICI 182,780 ICI 182780 ZD9238

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Gynecologic Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Allan L Covens, NRG Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gynecologic Oncology Group
• ClinicalTrials.gov Identifier: NCT00006903
• Other Study ID Numbers: GOG-0188; NCI-2009-00581; CDR0000068339; GOG-0188; GOG-0188; U10CA180868; U10CA027469
• First Posted: Jan 27, 2003
• Last Update Posted: Mar 20, 2019
• Last Verified: Mar 1, 2019

• Additional relevant MeSH terms: Carcinoma; Recurrence; Fulvestrant

Study Results

Participant Flow

Arm/Group Title	Ineligible	Estrogen Receptor Negative	Estrogen Receptor Positive
Arm/Group Description	Not eligible	Estrogen Receptor Negative, Faslodex® 250mg intramuscularly per month, minimum treatment period two cycles until disease progression or adverse effects prohibit further therapy	Estrogen Receptor Postive, Faslodex® 250mg intramuscularly per month, minimum treatment period two cycles until disease progression or adverse effects prohibit further therapy
Period Title: Overall Study
STARTED	10	24	33
COMPLETED	0	20	27
NOT COMPLETED	10	4	6

Baseline Characteristics

Arm/Group Title	Estrogen Receptor Negative	Estrogen Receptor Positive	Total
Arm/Group Description	Estrogen Receptor Negative, Faslodex® 250mg intramuscularly per month, minimum treatment period two cycles until disease progression or adverse effects prohibit further therapy	Estrogen Receptor Postive, Faslodex® 250mg intramuscularly per month, minimum treatment period two cycles until disease progression or adverse effects prohibit further therapy	Total of all reporting groups
Overall Participants	23	30	53
Age, Customized (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.9 (10.2)	65.9 (10.4)	64.6 (10.4)
Sex: Female, Male (Count of Participants)
Female	23 100%	30 100%	53 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Clinical Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Evaluated Every 8 Weeks
Description	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.

Outcome Measure Data

Analysis Population Description

Total number eligible and treated participants within groups defined by estrogen receptor status in metastatic tumor.

Arm/Group Title	Estrogen Receptor Negative	Estrogen Receptor Positive
Arm/Group Description	Estrogen Receptor Negative, Faslodex® 250mg intramuscularly per month, minimum treatment period two cycles until disease progression or adverse effects prohibit further therapy	Estrogen Receptor Postive, Faslodex® 250mg intramuscularly per month, minimum treatment period two cycles until disease progression or adverse effects prohibit further therapy
Measure Participants	23	30
Complete Response	0 0%	1 3.3%
Partial Response	0 0%	4 13.3%
Stable Disease	4 17.4%	9 30%
Disease Progression	18 78.3%	16 53.3%
Indeterminate	1 4.3%	0 0%

2. Primary Outcome

Title	Clinical Response by RECIST Criteria of Estrogen Receptor Expression
Description	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.

Outcome Measure Data

Analysis Population Description

Total number eligible and treated participants within groups defined by estrogen receptor status

Arm/Group Title	Estrogen Receptor Negative	Estrogen Receptor Positive
Arm/Group Description	Estrogen Receptor Negative, Faslodex® 250mg intramuscularly per month, minimum treatment period two cycles until disease progression or adverse effects prohibit further therapy	Estrogen Receptor Postive, Faslodex® 250mg intramuscularly per month, minimum treatment period two cycles until disease progression or adverse effects prohibit further therapy
Measure Participants	22	31
Complete Response	0 0%	1 3.3%
Partial Response	0 0%	4 13.3%
Stable Disease	4 17.4%	9 30%
Increasing Disease	17 73.9%	17 56.7%
Not Evaluated	1 4.3%	0 0%

3. Secondary Outcome

Title	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.
Description	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

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients.

Arm/Group Title	Grade 3 (CTCAE v 3.0)	Grade 4 (CTCAE v 3.0)	Grade 5
Arm/Group Description	Number of patients who experienced a grade 3 event using Common Terminology Criteria version 3.0	Number of patients who experienced a grade 4 event using Common Terminology Criteria version 3.0	Number of patients who experienced a grade 5 event using Common Terminology Criteria version 3.0
Measure Participants	47	47	47
Anemia	1 4.3%	1 3.3%	0 0%
Fatigue	1 4.3%	0 0%	0 0%
Gastrointestinal	1 4.3%	0 0%	0 0%
Nausea	3 13%	0 0%	0 0%
Vomiting	1 4.3%	0 0%	0 0%
Diarrhea	1 4.3%	0 0%	0 0%
Anorexia	2 8.7%	0 0%	0 0%
Metabolic	2 8.7%	0 0%	0 0%
Neurologic	2 8.7%	0 0%	0 0%
Depression	1 4.3%	0 0%	0 0%
Pain	1 4.3%	0 0%	0 0%
Dyspnea	1 4.3%	0 0%	0 0%
Thrombosis/embolism, regardless of attribution	0 0%	3 10%	1 1.9%

Adverse Events

Time Frame	Study treatment, and up to 30 days after stopping study treatment.
Adverse Event Reporting Description	The frequencies of maximum grade of serious adverse event or, for other adverse events, treatment-related adverse events by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Other Adverse Events reported are Grade 2 or higher.
Arm/Group Title	Faslodex
Arm/Group Description	Faslodex® 250mg intramuscularly per month, minimum treatment period two cycles until disease progression or adverse effects prohibit further therapy. Includes both Estrogen Receptor Positive and Estrogen Receptor Negative participants.
All Cause Mortality
	Faslodex
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Faslodex
	Affected / at Risk (%)	# Events
Total	11/53 (20.8%)
Gastrointestinal disorders
Nausea	2/53 (3.8%)
Vomiting	1/53 (1.9%)
Constipation	1/53 (1.9%)
Distention	1/53 (1.9%)
Obstruction, gi - small bowel nos	1/53 (1.9%)
General disorders
Death no ctcae term - disease progression	1/53 (1.9%)
Death no ctcae term - death nos	1/53 (1.9%)
Pain: abdominal pain nos	1/53 (1.9%)
Pain: pelvis	1/53 (1.9%)
Infections and infestations
Infection - other	1/53 (1.9%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/53 (3.8%)
Vascular disorders
Hemorrhage, gi - stomach	1/53 (1.9%)
Hemorrhage/pulmonary - respiratory tract	1/53 (1.9%)
Thrombosis/thrombus/embolism	3/53 (5.7%)
Other (Not Including Serious) Adverse Events
	Faslodex
	Affected / at Risk (%)	# Events
Total	28/53 (52.8%)
Blood and lymphatic system disorders
Anemia	9/53 (17%)
Neutropenia	1/53 (1.9%)
Ear and labyrinth disorders
Auditory	1/53 (1.9%)
Endocrine disorders
Hot Flashes/Flushes	6/53 (11.3%)
Eye disorders
Ocular/Visual	1/53 (1.9%)
Gastrointestinal disorders
Gastrointestinal	6/53 (11.3%)
Nausea	6/53 (11.3%)
Vomiting	3/53 (5.7%)
Diarrhea	1/53 (1.9%)
Anorexia	8/53 (15.1%)
General disorders
Constitutional	3/53 (5.7%)
Fatigue	13/53 (24.5%)
Pain	8/53 (15.1%)
Infections and infestations
Infection/Fever	1/53 (1.9%)
Metabolism and nutrition disorders
Metabolic	4/53 (7.5%)
Musculoskeletal and connective tissue disorders
Musculoskeletal	1/53 (1.9%)
Nervous system disorders
Neurologic	3/53 (5.7%)
Depression	6/53 (11.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	4/53 (7.5%)
Skin and subcutaneous tissue disorders
Injection Site Reaction	1/53 (1.9%)
Vascular disorders
Thrombosis/embolism	4/53 (7.5%)

Limitations/Caveats

Accrual was discontinued after completion of the first stage of accrual due to lack of study drug activity.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.