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

Sponsor

Angiochem Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT01480583

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

42.5

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Brain Metastases	Drug: GRN1005 Drug: Trastuzumab Drug: 18F-FLT	Phase 2

Detailed Description

Please see Brief Summary section.

Study Design

Study Type:

Interventional

Actual Enrollment :

85 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Oct 1, 2011

Actual Primary Completion Date :

Jun 1, 2015

Actual Study Completion Date :

Oct 1, 2015

Arms and Interventions

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: Trastuzumab 2 mg/kg IV every week or 6 mg/kg IV every 3 weeks per investigator choice Other Names: Herceptin Drug: 18F-FLT 5 mCi of 18F-FLT IV during Screening and during Cycle 1 Other Names: 18F-fluorothymidine

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: Trastuzumab

2 mg/kg IV every week or 6 mg/kg IV every 3 weeks per investigator choice

Other Names:

Herceptin

Drug: 18F-FLT

5 mCi of 18F-FLT IV during Screening and during Cycle 1

Other Names:

18F-fluorothymidine

Outcome Measures

Primary Outcome Measures

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

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Age ≥ 18 years
Histologically or cytologically-documented breast cancer (HER2 status and ER/PgR status must be known)
Brain metastasis from breast cancer with or without prior WBRT
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)
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
KPS ≥ 70%
Completed WBRT for intra-cranial lesions ≥ 28 days prior to first dose

Key Exclusion Criteria:

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