Details

Details

Title A Phase II, Open-Label, Multi-Center Study of ANG1005 in Breast Cancer Patients with Recurrent Brain Metastases

IRB ANG1114

CC 14-1095

Hospital Main Campus

Phase Phase 2

Disease Brain, Breast

Drug ANG1005

Description

Description

Primary Objectives
  • To determine the intracranial objective response rate (iORR) as evaluated by independent radiology facility (IRF)
Secondary Objectives
  • To determine the iORR as evaluated by Investigator
  • To determine the duration of intracranial objective response as evaluated by IRF and Investigator
  • To determine the median intracranial progression free survival (PFS) as evaluated by IRF and Investigator
  • To determine the intracranial PFS rates at 3, 6 and 12 months by IRF and Investigator
  • To determine the intracranial clinical benefit rates (CBR; CR+PR+SD) at 3 and 6 months by IRF and Investigator
  • To determine the 6-month overall survival rate
  • To determine the extracranial ORR and duration of response
  • Intracranial ORR by 2-dimensional (2-D) modified Response Assessment in Neuro-Oncology (RANO) criteria by IRF
  • To determine the safety and tolerability, including neurocognitive function
  • To determine the plasma pharmacokinetic profile of ANG1005
  • To assess for any potential immunogenicity of ANG1005
Exploratory Objectives
  • To determine the median overall survival
  • To determine the overall (intracranial and extracranial) PFS
  • To determine overall ORR
  • To explore potential diagnostic markers from tumor specimens
Inclusion Criteria

Inclusion Criteria

  1. Adult patients (≥ 18 years) who provide written informed consent.
  2. Histologically or cytologically-documented breast cancer (HER2, ER and PgR status must be known).
  3. Recurrent brain metastases from breast cancer.
  4. At least one radiologically-confirmed and measurable metastatic brain lesion (≥ 1.0 cm in the longest diameter is preferred but ≥ 0.5 cm in the longest diameter would be acceptable) by Gd-MRI of the brain within 14 days prior to first dose of ANG1005.
    • Non-SRS-treated brain lesion(s) are preferred as target lesion(s)
    • Lesion(s) which have been treated with SRS may be considered as target lesion(s) if there is unequivocal evidence of progression following SRS in the opinion of the investigator.
  5. Neurologically stable, defined as receiving stable doses of corticosteroids and anticonvulsants (not EIAEDs) for ≥ 1 week prior to first treatment at Cycle 1, Day 1.
  6. Karnofsky Performance Status (KPS) score ≥ 70 at screening and Cycle 1, Day 1.
  7. Adequate laboratory test results for organ systems, as follows:
    1. Hematology within 3 days prior to first dose of ANG1005 (Cycle 1, Day 1)
      • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
      • Hgb ≥ 9.0 g/dL
      • Platelets ≥ 100 x 109/L
    2. Serum Chemistry within 7 days prior to the first dose of ANG1005 (Cycle 1, Day 1)
      • Total bilirubin < 1.6 mg/dl or < the upper limit of normal (ULN). Serum direct bilirubin ≤ ULN for patients with documented Gilbert's syndrome.
      • Aspartate aminotransferase (AST; SGOT) and alanine aminotransferase (ALT; SGPT) < 2.5 x ULN. AST, ALT < 5 x ULN for patients with documented liver metastases
      • Alkaline phosphatase < 2.5 x ULN. For patients with documented liver or bone metastases < 5 x ULN
      • Serum creatinine < 1.5 mg/dL or creatinine clearance ≥ 45 mL/min
  8. Expected survival of at least 3 months
  9. Male and female patients who are not surgically sterile or post-menopausal must agree to use reliable methods of birth control for the duration of the study and for 90 days after the last administration of study treatment. Male partners of female patients should use condoms for the duration of the study, and for 90 days after the last administration of study treatment.
Exclusion Criteria

Exclusion Criteria

  1. Prior to the first day of dosing: radiotherapy (i.e., WBRT or SRS) within 3 months except palliative radiation to ≤20% of bone marrow. Surgery within 4 weeks.
  2. Prior/Concomitant therapy, prior to Cycle 1, Day 1 and throughout the study:
    • Investigational agents or chemotherapy within 1 week (if 5 half-lives ≤ 1 week), and within 4 weeks or 5 half-lives, whichever is shorter (if 5 half-lives > 1 week), or as per clinical judgment to allow for adverse event recovery.
    • Nitrosoureas within 6 weeks.
    • Non-nitrosurea-based cytotoxic chemotherapy within 2 weeks.
    • Biologic therapy and/or immunotherapy within 4 weeks, except for trastuzumab.
    • Hormone therapy within 5 half-lives, except for 1) ovarian suppression therapy and 2) maintenance systemic hormonal therapy which appears to be controlling systemic disease.
    • Current treatment with lapatinib. Previous treatment with lapatinib within 1 week prior to first day of dosing.
    • Exposure to P450 CYP 3A4 or 2C8 enzyme inducing antiepileptic drugs within 2 weeks prior to Cycle 1, Day 1.
    • Current use of St. John's wort or grapefruit/grapefruit juice within 1 week prior to Cycle 1, Day 1.
  3. Prior treatment with ANG1005/GRN1005.
  4. Evidence of symptomatic intracranial hemorrhage, as assessed by the Investigator.
  5. Pregnancy or lactation.
  6. Peripheral neuropathy ≥ Grade 2 (CTCAE v4.03).
  7. Inadequate bone marrow reserve (absolute neutrophil count < 1.5 x 109/L, platelet count < 100 x 109/L, and/or requiring regular blood transfusions to maintain hemoglobin > 9g/dL) prior to Cycle 1, Day 1.
  8. Any evidence of severe or uncontrolled diseases (e.g., unstable or uncompensated respiratory, cardiac (including arrhythmias), hepatic and/or renal diseases), as assessed by the Investigator.
  9. Patients with the presence of an infection including abscess or fistulae, or known infection with hepatitis B or C or HIV.
  10. History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of clinically significant interstitial lung disease on chest CT scan.
  11. Severe conduction disturbance including clinically significant QTc prolongation > 450 ms (unless pacemaker in place) or QTc prolongation ≥ 500 ms, regardless of clinical significance.
  12. CNS disease requiring immediate neurosurgery intervention (e.g., resection, shunt placement, etc.).
  13. Known severe hypersensitivity or allergy to paclitaxel or any of its components.