Clinical trial NCT01480583: GRN1005 Alone or in Combination With Trastuzumab in Breast Cancer Patients With Brain Metastases
Official title: A Phase II, Multi-center, Open-label Study Evaluating GRN1005 Alone or in Combination With Trastuzumab in Breast Cancer Patients With Brain Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Brain Metastases
Keywords: GRN1005
ANG1005
Peptide-Drug Conjugate (PDC)
LRP-1
Targeted Therapy
Breast Cancer
Brain Metastases
Brain Tumor
Blood Brain Barrier
Trastuzumab
Herceptin
Paclitaxel
Taxol
Breast cancer with brain metastases
Lead sponsor: Angiochem Inc
Sponsor class: INDUSTRY
First posted: 2011-11-29
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy, safety, and tolerability of GRN1005 in patients with brain metastases from breast cancer. For patients with HER2 positive metastatic breast cancer, GRN1005 will be assessed in combination with Trastuzumab (Herceptin®) as per standard-of-care practice.

In addition, this study will evaluate the ability of 18F-FLT to determine if the amount of change in the uptake in the brain metastases from breast cancer after GRN1005 treatment, correlates with intra-cranial response (for patients enrolled at NCI).

Detailed description: Please see Brief Summary section.

Eligibility criteria: Key Inclusion Criteria:

1. Age ≥ 18 years
2. Histologically or cytologically-documented breast cancer (HER2 status and ER/PgR status must be known)
3. Brain metastasis from breast cancer with or without prior WBRT
4. At least one radiologically-confirmed and measurable metastatic brain lesion (≥ 1.0 cm in the longest diameter) by Gd-MRI of the brain \< 14 days prior to first dose (Metastatic brain lesions previously treated with SRS may not be target or non-target lesions)
5. Patients must be neurologically stable: On stable doses of corticosteroids and anticonvulsants (not EIAEDs, including phenytoin, phenobarbitol, carbamazepine, fosphenytoin, primidone, oxcarbazepine) for ≥ 5 days prior to obtaining the baseline Gd-MRI of the brain and ≥ 5 days prior to first dose
6. KPS ≥ 70%
7. Completed WBRT for intra-cranial lesions ≥ 28 days prior to first dose

Key Exclusion Criteria:

1. NCI CTCAE v4.0 Grade ≥ 2 neuropathy
2. CNS disease requiring immediate neurosurgical intervention (e.g., resection, shunt placement, etc.)
3. Known leptomeningeal disease

Primary outcomes:
measure: Intra-cranial objective response rate in breast cancer patients with brain metastasis
timeFrame: Upon enrollment through end of study period (1 year after last patient is enrolled)
Secondary outcomes:
measure: Number of patients with adverse events as a measure of safety and tolerability of GRN1005 alone or in combination with Trastuzumab
timeFrame: Upon enrollment through end of study period (1 year after last patient is enrolled)
measure: Intra-cranial objective response duration
timeFrame: Upon enrollment through end of study period (1 year after last patient is enrolled)
measure: 3-month intra-cranial progression-free survival
timeFrame: Upon enrollment through end of study period (1 year after last patient is enrolled)
measure: Six month overall survival (OS)
timeFrame: Upon enrollment through end of study period (1 year after last patient is enrolled)
Other outcomes:
Locations:
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Rockville
country: United States
facility: NCI
state: Maryland
Study officials:
affiliation: Angiochem Inc
name: Betty Lawrence
role: STUDY_DIRECTOR
affiliation: Dana-Farber Cancer Institute
name: Nancy Lin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute (NCI)
name: Susan Bates, MD
role: PRINCIPAL_INVESTIGATOR
References: