Phase IIa Open Label, Randomized Clinical Trial to Study Vintafolide and Paclitaxel in Subjects with Advanced Triple Negative Breast Cancer Using SPECT/CT scan with Etarfolatide (EC20) for Subject Selectio

Active, not recruiting

• Conditions: Triple Negative Breast Cancer (advanced breast cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective); MedDRA version: 16.0Level: LLTClassification code 10072737Term: Advanced breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-005170-65-ES
• Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-07-12
• Last Update Posted: 7 October 2014

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: Female
• Target Recruitment: 102

Inclusion Criteria

1.Be a female subject with histologically or cytologically confirmed estrogen receptor negative, progesterone receptor negative, HER-2 negative (<3+ by IHC or fluorescence in situ hybridization [FISH] ratio <2.0 or per local standards) advanced breast cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
a.Estrogen receptor negative as determined by local
institutional laboratory criteria for estrogen receptor negativity. At a minimum, ER negative must be defined as <1 percent tumor cells positive by immunohistochemistry, irrespective of intensity [33].
b.Progesterone receptor negative as determined by local institutional laboratory criteria for progesterone receptor negativity. At a minimum, PR negative must be defined as <1 percent tumor cells positive by immunohistochemistry, irrespective of intensity [33].
2.Have developed progressive disease following at least one (and not more than four) prior chemotherapeutic regimens for breast cancer, which was administered for treatment of locally advanced, locally recurrent and/or metastatic disease.
a.At least one regimen must have included a taxane (e.g., paclitaxel, docetaxel) in any combination or order. (Patients with a history of prior taxane allergy or hypersensitivity are not eligible ? see exclusion criterion 7).
b.Prior taxane may have been administered during adjuvant and/or neoadjuvant therapy.
3.Have at least a single (RECIST 1.1 defined) measurable target lesion on a radiological evaluation that is conducted no more than 4 weeks prior to beginning of study therapy (vintafolide or vintafolide + paclitaxel or paclitaxel).
a.Measureable extranodal lesions are defined as those that can be accurately measured in at least one dimension, with longest diameter ? 10 mm by CT scan. Nodal lesions must be ? 15 mm on the short axis. Refer to the IIOM for further specifications.
b.Measurable lesions should not have received prior radiation therapy.
4.Have all tumor target lesions characterized as Folate Receptor positive using etarfolatide screening as assessed by a centralized radiology review.
a.Liver lesions are considered folate receptor positive.
5.Submit archival tumor tissue sample for analysis.
6.Not have received chemotherapy for 4 weeks prior to the initiation of study treatment and must have recovered to ? CTCAE grade 1 toxicities related to prior chemotherapies. Note: Subjects who have residual drug-induced neuropathy of ? Grade 2 will be eligible if it has been stable, and not worsening, for at least 30 days (see exclusion criterion #8).
7.Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
8.Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 30 days after the last dose of study medication (See Section 5.7.2.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >1 year.
9.Be ? 18 years of age on day of signing informed consent.
10.Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
11.Have vo

Exclusion Criteria

1.Has had chemotherapy, radiotherapy, or biological therapy (including monoclonal antibodies) within 4 weeks prior to drug administration or who has not recovered (?Grade 1 or baseline) from adverse experiences due to agents administered more than 4 weeks earlier.
2.Is currently participating or has participated in a study with an investigational compound or device within 28 days of initial dosing on this study.
3.Has received more than 4 prior cytotoxic regimens for metastatic disease. Adjuvant treatments provided to the subject would not count towards this criterion.
4.Has a primary central nervous system (CNS) tumor.
5.Has active CNS metastases and/or carcinomatous meningitis. However, subjects with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis; and (2) off steroids or on a stable dose of steroids for at least 2 weeks.
6.Has had prior therapy with vinorelbine (Navelbine®) or vinca-containing compounds.
7.Has known hypersensitivity to paclitaxel, docetaxel, other taxane therapies, drugs formulated with polyoxyethylated castor oil (Cremphor EL), vinblastine, other vinca-derived therapies, or their components or analogs.
8.Has pre-existing neuropathy > Grade 2.
a.Subjects who have residual drug-induced neuropathy of 2 will be eligible if it has been stable, and not worsening, for at least 30 days.
b.Data from an ongoing study with vintafolide and docetaxel suggest that neuropathy is not prohibitive with a vintafolide-taxane combination. Nonetheless, a theoretical concern exists because both classes of drugs are associated with neuropathy. If excessive neuropathy becomes evident with further clinical experience, patients with baseline grade 2 neuropathy may be excluded. The Sponsor will notify sites in writing if such action is necessary.
9.Has a recent (i.e., ? 6 weeks) history of abdominal surgery or peritonitis.
10.Has a bowel occlusion or sub-occlusion.
11.Has had prior abdominal or pelvic radiation therapy, or radiation therapy to > 10% of the bone marrow at any time in the past, or prior radiation therapy within the last three years to the breast / sternum, dermal lesions, head, or neck.
12.Requires anti-folate therapy for the management of co-morbid conditions (e.g., rheumatoid arthritis).
13.Has known psychiatric or substance abuse disorders that, in the opinion of the investigator, would interfere with cooperation with the requirements of the trial.
14.Is, at the time of signing the informed consent, a known regular user (including ?recreational use?) of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse.
15.Is expecting to reproduce within the projected duration of the study, and women who are pregnant or breastfeeding.
16.Is known to be Human Immunodeficiency Virus (HIV)-positive.
17.Has known active Hepatitis B or C.
18.Has symptomatic ascites or pleural effusion. However, a subject who is clinically stable following treatment for these conditions is eligible for the study.
19.Has had a prior stem cell or bone marrow transplant.
20.Has a history or current evidence of any condition, therapy, or lab abnormality that, in the opinion of the investigator, might confound the results of the study, interfere with the subject?s participation for the full duration of the study, or is not in the best interest of the

Study & Design

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