Clinical trial NCT01265927 (phase 1, status: completed)
Conditions: breast neoplasms
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: grn163l in combination with trastuzumab
SMILES: [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
Eligibility criteria:

        Inclusion Criteria:

          1. Males or females 18 years or older at the time of consent.

          2. ECOG performance status of 0-2 within 21 days of study registration.

          3. Histologically or cytologically confirmed adenocarcinoma of the breast with locally
             recurrent or metastatic disease. NOTE: locally recurrent disease must not be amenable
             to surgery or radiation with curative intent.

          4. Measurable or evaluable disease according to RECIST v1.1 within 35 days prior to study
             registration.

          5. Disease must be amenable to biopsy (image-guided or via direct visualization of
             superficial lesions) with minimal risk to the patient. NOTE: Patients with disease
             limited to the lung and/or pleura are excluded.

          6. Disease must be HER2+ as defined by IHC 3+ or FISH ratio > 2.0.

          7. Resistant to trastuzumab as defined as (1) progression within 12 months of completing
             adjuvant/neoadjuvant trastuzumab or (2) progression on trastuzumab administered for
             metastatic disease.

          8. Prior treatment with lapatinib or investigational HER2 targeted therapies is allowed
             but not required. There are no limits on the number of regimens or other prior
             anti-HER2 therapies patients have received.

          9. LVEF ≥ Lower Limit of Normal based on MUGA or ECHO within 35 days prior to study
             registration

         10. Females of childbearing potential and males must be willing to use an effective method
             of contraception from the time consent is signed until 6 months after treatment
             discontinuation. Methods of contraception include hormonal birth control (oral
             contraceptives, patch, injection, vaginal ring or implant), two barrier methods of
             birth control, abstinence and/or other methods as determined by the treating
             physician.

         11. Females of childbearing potential must have a negative pregnancy test within 14 days
             prior to registration for protocol therapy.

             NOTE: Females are considered of child bearing potential unless they are surgically
             sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral
             oophorectomy) or they are postmenopausal (> 12 months since last menses).

             Laboratory values must be obtained within 21 days of study registration:

         12. Absolute neutrophil count (ANC) ≥ 1.5 K/mm3

         13. Platelets ≥ 100 K/mm3

         14. Hemoglobin (Hgb) ≥ 9.0 g/dL (may be transfused)

         15. Serum creatinine < 3.0 mg/dL

         16. Total Bilirubin ≤ 1.5 x ULN

         17. AST/SGOT ≤ 2.5 x ULN. If liver metastases is present, AST ≤ 5 x ULN

         18. ALT, SGPT ≤ 2.5 x ULN. If liver metastases is present, ALT ≤ 5 x ULN

             Exclusion Criteria:

         19. No Investigational therapy within 4 weeks of study registration

         20. No hormonal therapy within 2 weeks of study registration

         21. No cytotoxic chemotherapy within 2 weeks of study registration.

         22. No prior treatment with GRN163L

         23. No prior history of severe reaction to trastuzumab, as determined by the treating
             physician.

         24. No history of clinically significant cardiac dysfunction, including:

             Current uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg), or
             unstable angina History of symptomatic CHF (Grade >3 by NCI CTCAE or Class >II by NYHA
             criteria [see Appendix IV]) or serious cardiac arrhythmia requiring treatment within
             12 months of study registration, with the exceptions of atrial fibrillation and
             paroxysmal supraventricular tachycardia History of myocardial infarction within 6
             months of study registration

         25. No history of cerebrovascular accident within 12 months of study registration

         26. No active CNS metastases. Patients with previously treated CNS metastases who do not
             require chronic steroids or anticonvulsants are eligible.

         27. Prior radiation therapy must not have involved > 25% of bone marrow due to potential
             myelosuppression with GRN163L. See bone marrow chart in Appendix III

             NOTE: Radiation therapy within 2 weeks of study registration is not allowed.

         28. Females must not be breastfeeding.

         29. No clinically significant active infection, as determined by the treating physician