Trial of Fulvestrant Plus Enzastaurin versus Fulvestrant Plus Placebo in Resistant Metastatic Breast Cancer

Phase 1

• Conditions: Aromatase Inhibitor-Resistant MetastaticBreast Cancer; MedDRA version: 14.1Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2006-005305-58-ES
• Lead Sponsor: illy S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-03-29
• Last Update Posted: 12 November 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 160

Inclusion Criteria

[1] Female patients with a histological-documented diagnosis of locally advanced or metastatic breast cancer. The primary or metastatic tumor must be ER and/or PtR receptor positive.
[2] Patients are resistant to AI therapy
? AI was administered in the adjuvant setting: patient should have been on treatment for at least 1 year and have had an objective recurrence during this treatment or in the first year after finishing it
? AI was administered in advanced disease:
? If patients have not received previous chemotherapy for MBC, they must have achieved a tumor response or stabilization lasting at least 6 months and have had an objective progression during treatment
? If patients have received previous chemotherapy for MBC, they can have 3 different situations (see Figure S023.2):
? Chemotherapy ? AI (as maintenance of response). They must have received the AI lasting at least 6 months and have had an objective progression during treatment
? Chemotherapy ? AI (at progression).
They must have achieved a tumor response or stabilization lasting at least 6 months and have had an objective progression during treatment ? AI ? Chemotherapy.
They must have achieved a tumor response or stabilization to the AI and have had an objective progression after chemotherapy.
[3] Females with postmenopausal status defined as:
? Age ? 60 years or age ? 45 years and 24 months from the last menstrual period with intact uterus ? (Or) follicle-stimulating hormone level within postmenopausal range
? (Or) prior radiation or surgical castration (such as bilateral salpingooophorectomy)
[4] Previous radiation therapy is allowed, but should have been limited and must not have included whole pelvis radiation. Patients must have recovered from the toxic effects of the treatment prior to study
enrollment (except for alopecia). Lesions that have been irradiated cannot be included as sites of measurable disease unless clear tumor progression, according to RECIST criteria, has been documented in
these lesions since the end of radiation therapy
[5] Measurable or nonmeasurable disease defined by:
? At least 1 unidimensionally measurable lesion meeting RECIST.
Positron emission tomography (PET) scans and ultrasounds may not be used
? At least 1 nonmeasurable lesion whose presence is assessable using standard techniques or a spiral CT scan even though the lesion is smaller than the minimum size required for measurability (PET scans and ultrasounds may not be used). Patients with bone lesion(s) in the absence of measurable disease can be recruited provided they can be evaluated by X-ray, CT or MRI (patients with lesions assessed only by bone scan cannot be included)
[6] Inclusion Criterion [6] has been deleted
[7] Have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) scale (Protocol Attachment S023.4; Oken et al. 1982)
[8] Have adequate organ function including the following:
Adequate bone marrow reserve: white blood cell (WBC) count ?3.0 x 109/L, absolute neutrophil count (ANC) ?1.5 x 109/L, platelet count ?75.0 x 109/L, and hemoglobin ?10.0 g/dL (?6.2 mmol/L)
Hepatic: bilirubin ?1.5 times the upper limit of normal (x ULN); alkaline phosphatase (ALP), aspartate transaminase (AST), and
alanine transaminase (ALT) ?2.5 × ULN or ?5 x ULN with liver metastases Renal: serum creatinine <1.5 x ULN.
[9] Are at least 18 years of age
[10] Have an estimated life expectancy of at least 24 weeks
[11] Exhibit patient compliance and geographic proximity th

Exclusion Criteria

[13] Have received treatment with more than 1 line of hormonal therapy in the metastatic setting
[14] Have had prior treatment with fulvestrant, or enzastaurin
[15] Exclusion Criterion [15] has been deleted
[16] Are receiving concurrent administration of any other antitumor therapy
[17] Have received treatment within the last 4 weeks with a drug that has not received regulatory approval for any indication at the time of study entry
[18] Have received supplemental estrogen or progesterone within 4 weeks prior to study entry
[19] HER2-positive patients determined by FISH (Fluorescence in situ hybridization) positive OR score 3+ IHC nohistochemistry)
[20] Are unable to discontinue use of anticoagulants
[21] Have hypercalcemia: corrected calcium >10% over ULN
[22] Have a second primary malignancy that is clinically detectable at the time of consideration for study enrollment
[23] Have documented central nervous system (CNS) metastases, symptomatic pulmonary lymphangitis, or involvement of more than 1/3 of the liver (that is, patients with rapidly progressive disease, or those whose assessment dictates that hemotherapy would be more appropriate)
[24] Have a serious concomitant systemic disorder (for example, active infection including HIV) incompatible with the study (at the discretion of investigator), previous history of bleeding diathesis, or coagulation
treatment
[25] Have a serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV (Protocol Attachment S023.6; Bruce RA
1956)
[26] Are unwilling or unable to discontinue use of carbamazepine, phenobarbital, or phenytoin at least 14 days prior to study therapy (refer to Section 5.7)
[27] Are unable to swallow tablets
[28] Exclusion Criterion [28] has been deleted
[29] Patients with known hypersensitivity to the drug or any of its components
[30] Patients with osteoporosis, defined as bone mineral density (BMD) T score <2.5 SD (standard deviation) or receiving treatment for osteoporosis. Note: Patients with BMD T score between 1 to 2.5 are
defined as osteopenia, which, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient?s ability to complete the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified