GRN1005 Alone or in Combination With Trastuzumab in Breast Cancer Patients With Brain Metastases

NCT01480583 | Completed Phase 2

• 1 other identifier: CP1005B016
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 2

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).

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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)

Study Arms (2)

GRN1005

EXPERIMENTAL

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; Drug: 18F-FLT

GRN1005 with trastuzumab

EXPERIMENTAL

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; Drug: Trastuzumab; Drug: 18F-FLT

Interventions

GRN1005 DRUG

550 mg/m2 IV every 3 weeks

Also known as: ANG1005

GRN1005; GRN1005 with trastuzumab

Trastuzumab DRUG

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

Also known as: Herceptin

GRN1005 with trastuzumab

18F-FLT DRUG

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

Also known as: 18F-fluorothymidine

GRN1005; GRN1005 with trastuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Angiochem Inc: lead

Study Sites (2)

Ingalls Memorial Hospital

Harvey, Illinois, 60426, United States

Location

NCI

Rockville, Maryland, 20892, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms

Interventions

paclitaxel-Angiopep-2 conjugate; Trastuzumab; alovudine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Betty Lawrence

  Angiochem Inc

  STUDY DIRECTOR

• Nancy Lin, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

• Susan Bates, MD

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2011
• First Posted: November 29, 2011
• Study Start: October 1, 2011
• Primary Completion: June 1, 2015
• Study Completion: October 1, 2015
• Last Updated: July 13, 2016

Record last verified: 2016-07

Locations

US (2)