GRN1005 in Non-Small Cell Lung Cancer (NSCLC) Patients With Brain Metastases (GRABM-L) (GRABM-L)

A Phase II, Multi-center, Open-label Study Evaluating the Efficacy and Safety of GRN1005 in Non-Small Cell Lung 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 non-small cell lung cancer (NSCLC).

Study Overview

• Status: Terminated
• Conditions: Non-small Cell Lung Cancer (NSCLC) With Brain Metastases
• Intervention / Treatment: Drug: GRN1005

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill Univ.
• United States
  • California
    • La Jolla, California, United States, 92093
      • Univ. of California San Diego
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Univ. Coloardo at Denver
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Univ.
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Univ. of Pittsburgh Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology

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. Adult patients (≥ 18 years)
2. Histologically or cytologically-documented NSCLC (EGFR mutation status must be known)

3. Brain metastases from NSCLC, which:

   have radiologically-progressed after WBRT or are present without prior WBRT

4. At least one radiologically-confirmed and measurable lesion (≥ 1.0 cm in the longest diameter) within14 days prior to the first dose of GRN1005 (Cycle 1, Day 1), as follows: an intra-cranial disease lesion (≥ 1.0 cm in the longest diameter) confirmed by Gd-MRI, or an extra-cranial disease lesion (≥ 1.0 cm in the longest diameter) confirmed by MRI or CT scan with contrast Prior stereotactic radiosurgery (SRS) is allowed; however, metastatic brain lesions previously treated with SRS are not allowed as target or as non-target lesions.
5. Patients must be neurologically stable, defined as being 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 of GRN1005 (Cycle 1, Day 1).
6. Karnofsky Performance Score (KPS) ≥ 80%
7. Completed WBRT for intra-cranial lesions ≥ 28 days prior to first dose of GRN1005 (with the exception of local radiation therapy for palliation to extra-cranial sites, i.e., bone). All clinically significant toxicities must have resolved to ≤ NCI CTCAE v4.0 Grade 1.0.

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 intra-cranial hemorrhage
4. Known leptomeningeal disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GRN1005 alone	Drug: GRN1005; 650 mg/m2 IV every 3 weeks; Other Names: ANG1005

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall (Intra-cranial and Extra-cranial) Objective Response Rate in Non-small Cell Lung Cancer (NSCLC) Patients With Brain Metastasis	Tumor response was assessed by Gd-MRI for intracranial lesions and CT/MRI with contrast of chest, abdomen, pelvis for extracranial lesions using modified OVERALL RECIST v1.1 as follows: Complete Response (CR), disappearance of all target and non-target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions and non-target lesions stable or decreased; Stable Disease (SD), < 30% decrease but <20% increase in target lesions and non-target lesions stable or decreased; Progressive disease (PD), >= 20% (>= 5 mm) increase in the sum of diameters of the target lesions, taking as reference the smallest sum on study, non-target lesions increased or appearance of a new lesion; Overall Response (OR) = CR + PR.	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	Upon enrollment through end of study period (1 year after last patient is enrolled)
Duration of Overall Objective Response	Upon enrollment through end of study period (1 year after last patient is enrolled)
Duration of Overall Progression Free Survival	Upon enrollment through end of study period (1 year after last patient is enrolled)
Six Month Overall Survival	Upon enrollment through end of study period (1 year after last patient is enrolled)

Collaborators and Investigators

• Sponsor: Angiochem Inc

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: December 20, 2011
• First Submitted That Met QC Criteria: December 20, 2011
• First Posted (Estimate): December 22, 2011

Study Record Updates

• Last Update Posted (Actual): January 22, 2019
• Last Update Submitted That Met QC Criteria: January 8, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: NSCLC; Non-Small Cell Lung Cancer; Brain Tumor; Paclitaxel; Taxol; Brain Metastases; Targeted Therapy; Blood Brain Barrier; ANG1005; GRN1005; LRP-1; Peptide-Drug Conjugate (PDC)
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: CP1005B017