GRN1005 for Brain Metastases From Breast or Lung Cancer

NCT01679743 | Withdrawn Phase 2

• 2 other identifiers: 12019912-C-0199
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: \- Brain metastases are cancer cells that have spread to the brain from primary cancers in other organs. These tumors can be removed surgically. However, researchers are trying to find better ways to treat brain metastases. A new drug, GRN1005, has been designed to cross into the brain and deliver the cancer treatment drug paclitaxel to treat tumors. Researchers want to see how well GRN1005 works on brain metastases from breast or lung cancer. Objectives: \- To test the safety and effectiveness of GRN1005 in treating brain metastases from breast or lung cancer. Eligibility: \- Individuals at least 18 years of age who have breast or lung cancer that has spread to the brain. Design:

• Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Tumor tissue samples may also be collected. Imaging studies will also be performed.
• Participants who have breast cancer will be divided into two groups. Those whose cancer contains the HER2 protein will be treated with the drug Herceptin as well as GRN1005. Those without HER2 will have only GRN1005.
• Participants who have lung cancer will also have only GRN1005.
• All participants will have two doses of GRN1005, each 3 weeks apart. On the day the second dose of GRN1005 is given, participants will undergo surgery to remove the brain tumors.
• Treatment will be monitored with frequent blood tests and imaging studies.

Conditions

Breast Cancer; Lung Neoplasms; Breast Neoplasms; Lung Cancer

Keywords

Metastatic Breast Cancer; Metastatic Lung Cancer; Monoclonal Antibody; 18FLT; Surgery

Outcome Measures

Primary Outcomes (1)

• Effect of GRN therapy on PET uptake after treatment cycle 1

  2 years

Study Arms (2)

A

EXPERIMENTAL

Breast Cancer Cohort

Drug: Trastuzumab; Drug: GRN 1005

B

EXPERIMENTAL

Non-Small Cell Lung Cancer Cohort

Drug: GRN 1005

Interventions

Trastuzumab DRUG

Trastuzumab will be administered after GRN1005 in patients with HER2+ metastatic breast cancer.

A

GRN 1005 DRUG

GRN1005 will be administered at a dose of 550 mg/m2 as an IV infusion at a rate of 8.0 - 8.5 mL/minute on Day 1 of 21-day cycle ( 3 days) and a second dose will be given on the day of surgery (day 21) 3-6 h prior to surgery.

A; B

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (greater than or equal to 18 years)
• Histologically or cytologically-documented breast cancer (HER2 status must be known) or NSCLC
• Presence of resectable brain metastases with or without prior radiotherapy. Patients must be greater than 28 days from WBRT or SRS
• Presence of resectable brain metastases, as assessed by neurosurgical evaluation. A brain tumor will be considered to be resectable for the purposes of the study if it is located in the cerebrum or the cerebellum. Tumors that are located in deep brain structures, including the medulla, pons, midbrain, thalamus, and basal ganglia will be considered non-resectable. The tumor must be solitary or, if not, accompanied by another tumor on the same side of the brain that is also considered to be resectable by the same criteria.
• At least one radiologically-confirmed and measurable metastatic brain lesion (greater than or equal to 1.0 centimeters in the longest diameter) by Gd-MRI of the brain less than 14 days prior to first dose of GRN1005 (Cycle 1, Day 1). The spatial resolution of the Philips Gemini TOF PET/CT is 4millimeters \[FWHM, (full width half maximum)\]. One cm is greater than 2 times this FWHM and it is anticipated that greater than 70% of the actual activity in the lesion will be visualized (i.e. recovered). It is expected that all lesions greater than or equal to 1 centimeters will have sufficient FLT uptake. If no lesions on the baseline image are visualized on FLT PET/CT, then post therapy FLT imaging will not be performed. These patients will be replaced.
• Patients must be neurologically stable, defined as being on stable doses of corticosteroids and anticonvulsants (not enzyme-inducing antiepileptic drugs (EIAEDs), including phenytoin, phenobarbitol, carbamazepine, fosphenytoin, primidone, oxcarbazepine) for greater than or equal to 5 days prior to obtaining the baseline Gd-MRI of the brain and greater than or equal to 5 days prior to first dose of GRN1005
• Karnofsky Performance Score (KPS) greater than or equal to 80% (which is equivalent to Eastern Cooperative Oncology Group \[ECOG\] Performance Status of 0 or 1)
• Life expectancy greater than 3 months
• Completed cytotoxic chemotherapy greater than or equal to 21 days (for an every 3-week regimen) or greater than or equal to 14 days (for an every 2-week or weekly regimen) prior to first dose of GRN1005 (Cycle 1, Day 1); all clinically significant toxicities (excluding alopecia) must have resolved to less than or equal to CTCAE v4.0 Grade 1.
• Completed treatment with non-cytotoxic systemic drugs (e.g., targeted drugs) greater than or equal to 14 days for small molecules and greater than or equal to 28 days for monoclonal antibodies (e.g., bevacizumab, with the exception of trastuzumab and bisphosphonates) prior to first dose of GRN1005 (Cycle 1, Day 1). All clinically significant toxicities (excluding alopecia) must have resolved to less than or equal to CTCAE v4.0 Grade 1.
• Adequate laboratory test results for organ systems less than equal 14 days prior to first dose of GRN1005, as follows:
• Absolute neutrophil count (ANC) greater than or equal to 1.5 times 10(9)/L
• Hgb greater than or equal to 9.0 grams per deciliter
• Platelets greater than or equal to 100 times 10(9)/L
• Total bilirubin less than 1.6 milligrams per deciliter or less than the upper limit of normal (ULN). Serum bilirubin less than 2 times ULN for patients with Gilbert s syndrome

You may not qualify if:

• NCI CTCAE v4.0 Grade greater than or equal to 2 neuropathy
• CNS disease requiring immediate neurosurgical intervention (e.g., resection, shunt placement, etc.)
• Known leptomeningeal disease
• Known severe hypersensitivity or allergy to paclitaxel or any of its components
• Treatment with P450 CYP 3A4 or 2C8 enzyme-inducing anticonvulsant drugs less than or equal to 14 days prior to first dose of GRN1005 (Cycle 1, Day 1)
• Patients with the presence of an infection including abscess or fistulae, or infection with hepatitis B or C or HIV
• Any evidence of severe or uncontrolled systemic disease, such as clinically significant cardiovascular (including arrhythmias), pulmonary, hepatic, renal, or metabolic disease; wound-healing disorders; ulcers; or bone fractures
• History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of clinically significant interstitial lung disease on chest CT scan
• Severe conduction disturbance including clinically significant QTc prolongation defined as a QTc greater than 450 milliseconds in women and QTc greater than 440 milliseconds in men (unless pacemaker in place).
• Women or men of reproductive potential not consenting to use double-barrier contraceptive methods (e.g., diaphragm plus condom) or abstinence during the study, from screening until 3 months after the last GRN1005 administration, and if applicable, for 6 months after the last trastuzumab administration
• Women who are pregnant or breast-feeding
• Prior GRN1005 treatment
• Allergy to gadolinium used in MRI

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Related Publications (3)

• Platta CS, Khuntia D, Mehta MP, Suh JH. Current treatment strategies for brain metastasis and complications from therapeutic techniques: a review of current literature. Am J Clin Oncol. 2010 Aug;33(4):398-407. doi: 10.1097/COC.0b013e318194f744.

  PMID: 19675447 BACKGROUND

• Steeg PS, Camphausen KA, Smith QR. Brain metastases as preventive and therapeutic targets. Nat Rev Cancer. 2011 May;11(5):352-63. doi: 10.1038/nrc3053. Epub 2011 Apr 7.

  PMID: 21472002 BACKGROUND

• Lagerwaard FJ, Levendag PC, Nowak PJ, Eijkenboom WM, Hanssens PE, Schmitz PI. Identification of prognostic factors in patients with brain metastases: a review of 1292 patients. Int J Radiat Oncol Biol Phys. 1999 Mar 1;43(4):795-803. doi: 10.1016/s0360-3016(98)00442-8.

  PMID: 10098435 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Lung Neoplasms

Interventions

Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract 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

• Susan E Bates, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 1, 2012
• First Posted: September 6, 2012
• Study Start: August 29, 2012
• Primary Completion: August 11, 2014
• Study Completion: August 11, 2014
• Last Updated: November 15, 2019

Record last verified: 2014-08-11