Non-small Cell Lung Cancer (NSCLC) With Brain Metastases
Conditions
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
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).
Interventions
DRUGGRN1005
650 mg/m2 IV every 3 weeks
Sponsors
Angiochem Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall (Intra-cranial and Extra-cranial) Objective Response Rate in Non-small Cell Lung Cancer (NSCLC) Patients With Brain Metastasis | upon enrollment through end of study period (1 year after last patient is enrolled) | 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. |
Secondary
| Measure | Time frame |
|---|---|
| Six Month Overall Survival | Upon enrollment through end of study period (1 year after last patient is enrolled) |
| 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) |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GRN1005 Alone GRN1005 alone
GRN1005: 650 mg/m2 IV every 3 weeks | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | GRN1005 Alone |
|---|---|
| Age, Continuous | 57.2 years STANDARD_DEVIATION 5.91 |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 16 |
| serious Total, serious adverse events | 9 / 16 |
Outcome results
Primary
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.
Time frame: upon enrollment through end of study period (1 year after last patient is enrolled)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GRN1005 Alone | Overall (Intra-cranial and Extra-cranial) Objective Response Rate in Non-small Cell Lung Cancer (NSCLC) Patients With Brain Metastasis | PR | 2 participants |
| GRN1005 Alone | Overall (Intra-cranial and Extra-cranial) Objective Response Rate in Non-small Cell Lung Cancer (NSCLC) Patients With Brain Metastasis | SD | 3 participants |
| GRN1005 Alone | Overall (Intra-cranial and Extra-cranial) Objective Response Rate in Non-small Cell Lung Cancer (NSCLC) Patients With Brain Metastasis | PD | 5 participants |
Secondary
Duration of Overall Objective Response
Time frame: Upon enrollment through end of study period (1 year after last patient is enrolled)
Population: Once the study was terminated, no further data on response was collected and there was insufficient number of participants with data collected for this outcome measure.
Secondary
Duration of Overall Progression Free Survival
Time frame: Upon enrollment through end of study period (1 year after last patient is enrolled)
Population: Once the study was terminated, no further efficacy data was collected and there was insufficient number of participants with data collected for this outcome measure.
Secondary
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Time frame: Upon enrollment through end of study period (1 year after last patient is enrolled)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GRN1005 Alone | Number of Patients With Adverse Events as a Measure of Safety and Tolerability | 16 participants |
Secondary
Six Month Overall Survival
Time frame: Upon enrollment through end of study period (1 year after last patient is enrolled)
Population: Once the study was terminated, no further survival data was collected and there was insufficient number of participants with data collected for this outcome measure.