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

• Sponsor: Angiochem Inc (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01497665
• Collaborator: (none)
• Enrollment: 16
• Locations: 10
• Arm: 1
• Duration (Months): 15
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0.1

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 non-small cell lung cancer (NSCLC).

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer (NSCLC) With Brain Metastases	Drug: GRN1005	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Nov 1, 2011
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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)]

2. Duration of Overall Objective Response [Upon enrollment through end of study period (1 year after last patient is enrolled)]

3. Duration of Overall Progression Free Survival [Upon enrollment through end of study period (1 year after last patient is enrolled)]

4. Six Month Overall Survival [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: No

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

1. 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.

2. 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).

3. Karnofsky Performance Score (KPS) ≥ 80%

4. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ. of California San Diego	La Jolla	California	United States	92093
2	Univ. Coloardo at Denver	Aurora	Colorado	United States	80045
3	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33612
4	Northwestern Univ.	Chicago	Illinois	United States	60611
5	Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
6	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
7	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
8	Univ. of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15232
9	Tennessee Oncology	Nashville	Tennessee	United States	37203
10	McGill Univ.	Montreal	Quebec	Canada	H2W 1S6

Sponsors and Collaborators

• Angiochem Inc

Investigators

• Study Director: Betty Lawrence, Angiochem Inc
• Principal Investigator: Patrick Wen, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Angiochem Inc
• ClinicalTrials.gov Identifier: NCT01497665
• Other Study ID Numbers: CP1005B017
• First Posted: Dec 22, 2011
• Last Update Posted: Jan 22, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by Angiochem Inc: 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
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Neoplasms, Second Primary; Brain Neoplasms

Study Results

Participant Flow

Arm/Group Title	GRN1005 Alone
Arm/Group Description	GRN1005 alone GRN1005: 650 mg/m2 IV every 3 weeks
Period Title: Overall Study
STARTED	16
Completed Effifcacy Assessment	10
COMPLETED	16
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	GRN1005 Alone
Arm/Group Description	GRN1005 alone GRN1005: 650 mg/m2 IV every 3 weeks
Overall Participants	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.2 (5.91)
Sex: Female, Male (Count of Participants)
Female	10 62.5%
Male	6 37.5%
Region of Enrollment (participants) [Number]
United States	16 100%

Outcome Measures

1. Primary Outcome

Title	Overall (Intra-cranial and Extra-cranial) Objective Response Rate in Non-small Cell Lung Cancer (NSCLC) Patients With Brain Metastasis
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GRN1005 Alone
Arm/Group Description	GRN1005 alone GRN1005: 650 mg/m2 IV every 3 weeks
Measure Participants	10
PR	2 12.5%
SD	3 18.8%
PD	5 31.3%

2. Secondary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GRN1005 Alone
Arm/Group Description	GRN1005 alone GRN1005: 650 mg/m2 IV every 3 weeks
Measure Participants	16
Number [participants]	16 100%

3. Secondary Outcome

Title	Duration of Overall Objective Response
Time Frame	Upon enrollment through end of study period (1 year after last patient is enrolled)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	GRN1005 Alone
Arm/Group Description	GRN1005 alone GRN1005: 650 mg/m2 IV every 3 weeks
Measure Participants	0

4. Secondary Outcome

Title	Duration of Overall Progression Free Survival
Time Frame	Upon enrollment through end of study period (1 year after last patient is enrolled)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	GRN1005 Alone
Arm/Group Description	GRN1005 alone GRN1005: 650 mg/m2 IV every 3 weeks
Measure Participants	0

5. Secondary Outcome

Title	Six Month Overall Survival
Time Frame	Upon enrollment through end of study period (1 year after last patient is enrolled)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	GRN1005 Alone
Arm/Group Description	GRN1005 alone GRN1005: 650 mg/m2 IV every 3 weeks
Measure Participants	0

Adverse Events

Time Frame	After informed consent, prior to initiation of GRN1005: only SAEs caused by a protocol-mandated intervention. After initiation of GRN1005: all AEs and SAEs until 30 days following the last administration of study drug.
Adverse Event Reporting Description	All SAEs and all Other (not including serious) AEs are reported regardless of attribution.
Arm/Group Title	GRN1005 Alone
Arm/Group Description	GRN1005 alone GRN1005: 650 mg/m2 IV every 3 weeks
All Cause Mortality
	GRN1005 Alone
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	GRN1005 Alone
	Affected / at Risk (%)	# Events
Total	9/16 (56.3%)
Blood and lymphatic system disorders
Febrile neutropenia	3/16 (18.8%)
Neutropenia	3/16 (18.8%)
Thrombocytopenia	1/16 (6.3%)
Gastrointestinal disorders
Dysphagia	1/16 (6.3%)
Vomiting	1/16 (6.3%)
General disorders
Mucosal inflammation	1/16 (6.3%)
Infections and infestations
Lung infection	1/16 (6.3%)
Pneumonia	1/16 (6.3%)
Injury, poisoning and procedural complications
Fall	1/16 (6.3%)
Investigations
White blood cell count decreased	1/16 (6.3%)
Metabolism and nutrition disorders
Dehydration	1/16 (6.3%)
Nervous system disorders
Convulsion	1/16 (6.3%)
Respiratory, thoracic and mediastinal disorders
Aspiration	1/16 (6.3%)
Respiratory failure	1/16 (6.3%)
Other (Not Including Serious) Adverse Events
	GRN1005 Alone
	Affected / at Risk (%)	# Events
Total	16/16 (100%)
Blood and lymphatic system disorders
Anemia	3/16 (18.8%)
Leukopenia	4/16 (25%)
Neutropenia	7/16 (43.8%)
Thombocytopenia	3/16 (18.8%)
Leukocytosis	1/16 (6.3%)
Ear and labyrinth disorders
Deafness	1/16 (6.3%)
Gastrointestinal disorders
Diarrhea	4/16 (25%)
Dyspepsia	2/16 (12.5%)
Nausea	4/16 (25%)
Vomiting	2/16 (12.5%)
Abdominal pain	2/16 (12.5%)
Constipation	1/16 (6.3%)
Faecal incontinence	1/16 (6.3%)
Lip dry	1/16 (6.3%)
Oral pain	1/16 (6.3%)
General disorders
Asthenia	2/16 (12.5%)
Oedema peripheral	4/16 (25%)
Face edema	2/16 (12.5%)
Fatigue	6/16 (37.5%)
Mucosal inflammation	4/16 (25%)
Pain	2/16 (12.5%)
Pyrexia	1/16 (6.3%)
Gait disturbance	2/16 (12.5%)
Influenza like illness	1/16 (6.3%)
Malaise	1/16 (6.3%)
Immune system disorders
Drug hypersensitivity	1/16 (6.3%)
Infections and infestations
Candidiasis	1/16 (6.3%)
Oral candidiasis	2/16 (12.5%)
Urinary tract infection	3/16 (18.8%)
Mucosal infection	1/16 (6.3%)
Rash pustular	1/16 (6.3%)
Upper respiratory tract infection	1/16 (6.3%)
Injury, poisoning and procedural complications
Fall	2/16 (12.5%)
Contusion	1/16 (6.3%)
Spinal compression fracture	1/16 (6.3%)
Investigations
Lymphocyte count decreased	1/16 (6.3%)
Neutrophil count decreased	1/16 (6.3%)
Platelet count decreased	1/16 (6.3%)
Weight decreased	1/16 (6.3%)
White blood cell count decreased	3/16 (18.8%)
White blood cell count increased	1/16 (6.3%)
Metabolism and nutrition disorders
Decreased appetite	3/16 (18.8%)
Dehydration	4/16 (25%)
Hypoalbuminemia	2/16 (12.5%)
Hypokalemia	2/16 (12.5%)
Hyponatraemia	1/16 (6.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/16 (12.5%)
Pain in extremity	4/16 (25%)
Back pain	3/16 (18.8%)
Flank pain	1/16 (6.3%)
Muscular weakness	1/16 (6.3%)
Myopathy	1/16 (6.3%)
Neck pain	1/16 (6.3%)
Nervous system disorders
Balance disorder	1/16 (6.3%)
Dizziness	4/16 (25%)
Dysgeusia	1/16 (6.3%)
Hemorrhage intracranial	1/16 (6.3%)
Hypoesthesia	2/16 (12.5%)
Neuralgia	1/16 (6.3%)
Neuropathy peripheral	6/16 (37.5%)
Paraesthesia	4/16 (25%)
Peripheral motor neuropathy	1/16 (6.3%)
Peripheral sensory neuropathy	2/16 (12.5%)
Headache	4/16 (25%)
Ataxia	2/16 (12.5%)
Hemiparesis	1/16 (6.3%)
Sensory loss	1/16 (6.3%)
Syncope	1/16 (6.3%)
Tremor	1/16 (6.3%)
Psychiatric disorders
Confusional state	3/16 (18.8%)
Dysphoria	1/16 (6.3%)
Insomnia	2/16 (12.5%)
Delirium	1/16 (6.3%)
Depression	1/16 (6.3%)
Renal and urinary disorders
Nocturia	1/16 (6.3%)
Urinary incontinence	2/16 (12.5%)
Reproductive system and breast disorders
Sexual dysfunction	1/16 (6.3%)
Respiratory, thoracic and mediastinal disorders
Cough	2/16 (12.5%)
Dysphonia	1/16 (6.3%)
Dyspnoea	3/16 (18.8%)
Oropharyngeal pain	2/16 (12.5%)
Pulmonary congestion	1/16 (6.3%)
Dry throat	1/16 (6.3%)
Dyspnoea exertional	1/16 (6.3%)
Haemoptysis	1/16 (6.3%)
Hypoxia	1/16 (6.3%)
Nasal congestion	1/16 (6.3%)
Upper-airway cough syndrome	1/16 (6.3%)
Wheezing	1/16 (6.3%)
Respiratory tract congestion	1/16 (6.3%)
Skin and subcutaneous tissue disorders
Alopecia	3/16 (18.8%)
Dry skin	1/16 (6.3%)
Rash	3/16 (18.8%)
Pruritus	1/16 (6.3%)
Skin ulcer	1/16 (6.3%)
Dermatitis	1/16 (6.3%)
Vascular disorders
Hypotension	2/16 (12.5%)
Hypertension	1/16 (6.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.