[hutchibk]

http://www.clinicaltrials.gov/ct2/sh...%2F2010&rank=1


Investigational Site Highland, California, United States, 92346
Investigational Site Stockton, California, United States, 95204
Investigational Site Denver, Colorado, United States, 80220
Investigational Site Davie, Florida, United States, 33328
Investigational Site Chicago, Illinois, United States, 60612
Investigational Site Lafayette, Indiana, United States, 47905
Investigational Site Cedar Rapids, Iowa, United States, 52403
Investigational Site Louisville, Kentucky, United States, 40245
Investigational Site Detroit, Michigan, United States, 48201
Investigational Site St. Louis, Missouri, United States, 63141
Investigational Site Charleston, South Carolina, United States, 29403
Investigational Site Nashville, Tennessee, United States, 37203
Investigational Site San Antonio, Texas, United States, 78229
Investigational Site Fairfax, Virginia, United States, 22031

Criteria
Inclusion Criteria:

• Histologically or cytologically documented breast cancer
• Locally advanced or metastatic breast cancer
• HER2-positive breast cancer documented as FISH-positive, IHC 3 + or CISH-positive by local laboratory assessment
• Prior treatment with an anthracycline and a taxane given in the neoadjuvant, adjuvant, or metastatic setting, or as treatment for unresectable locally advanced disease
• Prior treatment with capecitabine or infusional 5-fluorouracil and at least two HER2-targeted agents, including trastuzumab and lapatinib, in the metastatic and/or unresectable locally advanced setting
• Patients must have had disease progression during their most recent treatment regimen
• Adequate hematologic and end organ function
• Agreement to use an effective form of birth control throughout the study
• Life expectancy ≥ 90 days as assessed by the investigator

Exclusion Criteria:

• Less than 14 days from the first study treatment since the last anti-cancer therapy, including chemotherapy, biologic, experimental, immune, hormonal or endocrine therapy
• Prior T-DM1 therapy
• History of exposure to cumulative doses of select anthracyclines
• History of intolerance or hypersensitivity to trastuzumab, murine proteins, or any of the excipients, that resulted in trastuzumab being permanently discontinued
• Brain metastases that are untreated or progressive or currently require any type of therapy, including radiation, surgery, and/or steroids to control symptoms from brain metastases within 30 days before the first study treatment
• Peripheral neuropathy of Grade ≥ 3 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0, at the time of the first study treatment
• History of clinically significant cardiac dysfunction
• Current known active infection with HIV, hepatitis B virus, or hepatitis C virus
• Current severe, uncontrolled systemic disease
• Major surgical procedure or significant traumatic injury within 28 days prior to first study treatment
• Pregnancy or lactation

I personally believe this lies mostly in the hands/blame of the FDA for applying extremely binding overall survival criteria (which they also insanely qualified by stating "regardless of HER2 status", WTF?) for approval that they don't/haven't necessarily require(d) for drugs for other cancers as well as for other breast cancer drugs...

I imagine that Genentech/Roche and the makers of Maytanzine 1) simply can't afford to offer it in compassionate use for an indeterminate amount of time to a full complement of locations 2) aren't able to manufacture enough of it to offer in compassionate use as well as all the trials for an indeterminate amount of time... due to the FDA rejection of the BLA in July. I believe they intended to open it up to compassionate use to bridge the period of time it would take for the FDA to approve it and license it, which they expected to be a 6 mo to 1 yr process at the longest. They do not want to close the EAP, but they need to keep it limited and small in scope because they don't expect to be allowed to go back for approval for 18 months or more at this point.