Clinical trial NCT01497665: GRN1005 in Non-Small Cell Lung Cancer (NSCLC) Patients With Brain Metastases (GRABM-L)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer (NSCLC) With Brain Metastases
Keywords: GRN1005
ANG1005
LRP-1
Targeted Therapy
Brain Tumor
Blood Brain Barrier
Peptide-Drug Conjugate (PDC)
Brain Metastases
Paclitaxel
Taxol
NSCLC
Non-Small Cell Lung Cancer
Lead sponsor: Angiochem Inc
Sponsor class: INDUSTRY
First posted: 2011-12-22
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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 non-small cell lung cancer (NSCLC).


Eligibility criteria: 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

Primary outcomes:
measure: Overall (Intra-cranial and Extra-cranial) Objective Response Rate in Non-small Cell Lung Cancer (NSCLC) 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
timeFrame: Upon enrollment through end of study period (1 year after last patient is enrolled)
measure: Duration of Overall Objective Response
timeFrame: Upon enrollment through end of study period (1 year after last patient is enrolled)
measure: Duration of Overall Progression Free Survival
timeFrame: Upon enrollment through end of study period (1 year after last patient is enrolled)
measure: Six Month Overall Survival
timeFrame: Upon enrollment through end of study period (1 year after last patient is enrolled)
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Univ. of California San Diego
state: California
city: Aurora
country: United States
facility: Univ. Coloardo at Denver
state: Colorado
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern Univ.
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Pittsburgh
country: United States
facility: Univ. of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Montreal
country: Canada
facility: McGill Univ.
state: Quebec
Study officials:
affiliation: Angiochem Inc
name: Betty Lawrence
role: STUDY_DIRECTOR
affiliation: Dana-Farber Cancer Institute
name: Patrick Wen, MD
role: PRINCIPAL_INVESTIGATOR
References: