Safety and Efficacy Study of Vintafolide and Vintafolide Plus Paclitaxel Compared to Paclitaxel Alone in Participants With Triple Negative Breast Cancer (TNBC) (MK-8109-004)

NCT01953536 | Withdrawn Phase 2

• 2 other identifiers: 8109-0042012-005170-65
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to assess the efficacy and safety of vintafolide alone compared to vintafolide plus paclitaxel and paclitaxel alone in participants with with 100% positive folate receptor (FR) triple negative breast cancer (TNBC). The primary hypothesis of this study is the vintafolide alone and/or vintafolide + paclitaxel will improve progression free survival (PFS) in participants with FR (100%) TNBC compared to paclitaxel alone.

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Up to 60 months

Secondary Outcomes (3)

• Objective Response Rate (Complete Response [CR] + Partial Response [PR])

  Up to 60 months

• Clinical Benefit Rate (CR + PR + Stable Disease [SD] for >=6 months)

  Up to 60 months

• Overall Survival (OS)

  Up to 60 months

Study Arms (3)

Vintafolide

EXPERIMENTAL

Participants receive intravenous (IV) vintafolide 2.5 mg on Days 1, 3, 5, 15, 17, and 19 of a 28-day cycle.

Drug: Vintafolide 2.5 mg; Drug: Etarfolatide; Drug: Folic acid

Vintafolide + Paclitaxel

EXPERIMENTAL

Participants receive IV vintafolide 2.5 mg on Days 1, 3, 5, 15, 17, and 19 of one 28-day cycle and receive IV paclitaxel on Days 1, 8, 15, and 22 of a 28-day cycle.

Drug: Vintafolide 2.5 mg; Drug: Paclitaxel 80 mg/m^2; Drug: Etarfolatide; Drug: Folic acid; Drug: Premedication for Paclitaxel

Paclitaxel

ACTIVE COMPARATOR

Participants receive IV paclitaxel on Days 1, 8, 15, and 22 of a 28-day cycle.

Drug: Paclitaxel 80 mg/m^2; Drug: Etarfolatide; Drug: Folic acid; Drug: Premedication for Paclitaxel

Interventions

Vintafolide 2.5 mg DRUG

During treatment, participants receive IV vintafolide 2.5 mg.

Vintafolide; Vintafolide + Paclitaxel

Paclitaxel 80 mg/m^2 DRUG

During treatment, participants receive IV paclitaxel 80 mg/m\^2.

Paclitaxel; Vintafolide + Paclitaxel

Etarfolatide DRUG

During screening and prior to screening CT scan, participants receive an IV injection of 0.1 mg etarfolatide radiolabeled with 20 to 25 milliCuries of technetium-99m.

Paclitaxel; Vintafolide; Vintafolide + Paclitaxel

Folic acid DRUG

During screening and prior to etarfolatide injection and screening CT scan, participants receive an IV injection of 0.5 mg folic acid.

Paclitaxel; Vintafolide; Vintafolide + Paclitaxel

Premedication for Paclitaxel DRUG

During treatment, participants receive dexamethasone 20 mg orally 12 to 6 hours prior to paclitaxel; OR promethazine 25 mg or 50 mg IV 30 to 60 minutes prior to paclitaxel; OR cimetidine 300 mg IV or ranitidine 50 mg IV 30 to 60 minutes prior to paclitaxel.

Paclitaxel; Vintafolide + Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female with histologically or cytologically confirmed estrogen receptor negative, progesterone receptor negative, human epidermal growth factor receptor 2 (HER-2) negative advanced breast cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
• Has developed progressive disease following at least 1 (and not more than 4) prior chemotherapeutic regimens for breast cancer, which was administered for treatment of locally advanced, locally recurrent and/or metastatic disease. \[At least 1 regimen must have included a taxane (e.g., paclitaxel, docetaxel) in any combination or order.\]
• Has at least a single measurable target lesion on a radiological evaluation that is conducted no more than 4 weeks prior to beginning of study drug. (Measurable lesions should not have received prior radiation therapy.)
• Has not received chemotherapy for 4 weeks prior to the initiation of study drug and must have recovered to ≤Common Terminology Criteria for Adverse Events (CTCAE) grade 1 toxicities related to prior chemotherapies.
• Female participants of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study drug.
• Female participants 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 drug.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has no history of a prior malignancy with the exception of cervical intraepithelial neoplasia; basal cell carcinoma of the skin or has undergone potentially curative therapy with no evidence of that disease for 5 years.
• Has adequate organ function.

You may not qualify if:

• Has had chemotherapy, radiotherapy, or biological therapy (including monoclonal antibodies) within 4 weeks prior to study drug administration or has not recovered (≤Grade 1 or baseline) from adverse experiences due to agents administered more than 4 weeks earlier.
• Is currently participating or has participated in a study with an investigational compound or device within 28 days of initial dosing on this study.
• Has received more than 4 prior cytotoxic regimens for metastatic disease. Adjuvant treatments would not count towards this criterion.
• Has a primary central nervous system (CNS) tumor.
• Has active CNS metastases and/or carcinomatous meningitis.
• Has had prior therapy with vinorelbine (Navelbine®) or vinca-containing compounds.
• Has known hypersensitivity to paclitaxel, docetaxel, other taxane therapies, drugs formulated with polyoxyethylated castor oil (Cremophor EL®), vinblastine, other vinca derived therapies, or their components or analogs.
• Has pre-existing neuropathy \>Grade 2.
• Has a recent (i.e., ≤6 weeks) history of abdominal surgery or peritonitis.
• Has a bowel occlusion or sub-occlusion.
• 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 3 years to the breast/sternum, dermal lesions, head, or neck.
• Requires anti-folate therapy.
• Has known psychiatric or substance abuse disorders.
• Is 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.
• Is expecting to reproduce within the projected duration of the study, and women who are pregnant or breastfeeding.

Sponsors & Collaborators

• Endocyte: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

EC145; Paclitaxel; technetium 99m etarfolatide; Folic Acid; Premedication

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2013
• First Posted: October 1, 2013
• Study Start: April 1, 2014
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: December 19, 2014

Record last verified: 2014-12