GRN1005 Alone or in Combination With Trastuzumab in Breast Cancer Patients With Brain Metastases (GRABM-B)

A Phase II, Multi-center, Open-label Study Evaluating GRN1005 Alone or in Combination With Trastuzumab in Breast Cancer Patients With Brain Metastases

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).

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Brain Metastases
• Intervention / Treatment: Drug: GRN1005; Drug: 18F-FLT; Drug: Trastuzumab

Detailed Description

Please see Brief Summary section.

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hospital
  • Maryland
    • Rockville, Maryland, United States, 20892
      • NCI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GRN1005; GRN1005 alone in HER2- MBC patients with brain mets. 18F-FLT may also be administered to this arm (if patient enrolled at NCI)	Drug: GRN1005; 550 mg/m2 IV every 3 weeks; Other Names: ANG1005; Drug: 18F-FLT; 5 mCi of 18F-FLT IV during Screening and during Cycle 1; Other Names: 18F-fluorothymidine
Experimental: GRN1005 with trastuzumab; GRN1005 in combination with trastuzumab in MBC patients with brain mets 18F-FLT may also be administered to this arm (if patient enrolled at NCI)	Drug: GRN1005; 550 mg/m2 IV every 3 weeks; Other Names: ANG1005; Drug: 18F-FLT; 5 mCi of 18F-FLT IV during Screening and during Cycle 1; Other Names: 18F-fluorothymidine; Drug: Trastuzumab; 2 mg/kg IV every week or 6 mg/kg IV every 3 weeks per investigator choice; Other Names: Herceptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Intra-cranial objective response rate in breast cancer patients with brain metastasis	Upon enrollment through end of study period (1 year after last patient is enrolled)

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with adverse events as a measure of safety and tolerability of GRN1005 alone or in combination with Trastuzumab	Upon enrollment through end of study period (1 year after last patient is enrolled)
Intra-cranial objective response duration	Upon enrollment through end of study period (1 year after last patient is enrolled)
3-month intra-cranial progression-free survival	Upon enrollment through end of study period (1 year after last patient is enrolled)
Six month overall survival (OS)	Upon enrollment through end of study period (1 year after last patient is enrolled)

Collaborators and Investigators

• Sponsor: Angiochem Inc
• Investigators: Principal Investigator: Susan Bates, MD, National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: November 16, 2011
• First Submitted That Met QC Criteria: November 23, 2011
• First Posted (Estimate): November 29, 2011

Study Record Updates

• Last Update Posted (Estimate): July 13, 2016
• Last Update Submitted That Met QC Criteria: July 11, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Breast Cancer; Brain Tumor; Trastuzumab; Paclitaxel; Taxol; Brain Metastases; Herceptin; Targeted Therapy; Blood Brain Barrier; ANG1005; GRN1005; Breast cancer with brain metastases; LRP-1; Peptide-Drug Conjugate (PDC)
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Breast Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Neoplasms, Second Primary; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab; Alovudine
• Other Study ID Numbers: CP1005B016