- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02312622
Phase 2 Etirinotecan Pegol in Refractory Brain Metastases & Advanced Lung Cancer / Metastatic Breast Cancer
A Phase 2 Study of Etirinotecan Pegol (NKTR-102) in Patients With Refractory Brain Metastases and Advanced Lung Cancer or Metastatic Breast Cancer (MBC)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Primary Objective:
For cohort A and Cohort C, to determine the central nervous system (CNS) disease control rate (number of patients with stable disease or partial response or complete response / total number of treated patients) at 12 weeks following treatment with etirinotecan pegol in patients with advanced non-small cell lung cancer (NSCLC) or with metastatic brain cancer (mBC) with refractory brain metastases
Secondary Objectives:
Cohorts A and C:
- To measure the overall disease control rate and response rate for patients receiving study therapy
- To measure the systemic (non-CNS) disease control rate and response rate for patients receiving study therapy
- To observe the progression free survival of the study population
- To observe the overall survival of the study population
Cohort B:
• To observe CNS and systemic disease control in small cell lung cancer (SCLC)
Cohorts A, B and C:
• To determine the safety profile of etirinotecan pegol
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
California
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Stanford, California, United States, 94305
- Stanford University, School of Medicine
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- At least 18 years of age.
- Life expectancy of 3 months or longer.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Advanced or refractory cancer, consisting of
- Metastatic breast cancer (mBC) for which single-agent cytotoxic chemotherapy is indicated. OR
Histologically-proven metastatic lung cancer:
- Non-small cell lung cancer (NSCLC) as Stage IV disease or recurrent metastatic disease [per lung cancer tumor, node and metastasis (TNM) classification system, 7th ed] (Cohort A) OR
- Small cell lung cancer (SCLC) as extensive stage or recurrent metastatic disease (cohort B), including tumors with mixed small cell and non-small cell elements.
Prior chemotherapy (at least one of the following):
- At least one line of prior systemic chemotherapy
- At least one line of prior targeted treatment for metastatic disease Adjuvant systemic chemotherapy within prior 6 months Prior treatment for metastatic breast cancer (mBC) must have included taxane-based regimen
Prior chemotherapy, including other investigational therapy, has been completed prior to initiation of study treatment, according to the following:
- ≥ 2 weeks if immediately preceding treatment was chemotherapy/targeted therapy administered on a daily or weekly schedule
- ≥ 3 weeks if immediately preceding treatment was chemotherapy/targeted therapy administered every 2 weeks
- ≥ 4 weeks if immediately preceding treatment was chemotherapy/targeted therapy administered every 3 weeks Previously received at least one CNS directed treatment (such as surgery or radiation) OR not be eligible for CNS stereotactic radiosurgery Measurable CNS disease, either previously untreated (not counting systemic therapy), or progressed following previous radiation treatment. Lesions that have progressed after prior radiosurgery should not be selected as measurable disease if they are suspected of being radionecrosis.
The following measurement criteria are required, as visualized by contrast-enhanced MRI with slice thickness of ≤ 1.5 mm, unless absence of contrast or thicker slices is specifically authorized by Protocol Director. Measurements do not include tumor edema.
- At least one CNS tumor measuring ≥ 10 mm in longest diameter, OR
- At least one CNS tumor measuring 5-9 mm in longest diameter, plus one or two additional CNS tumors measuring ≥ 3 mm in longest diameter, for which the sum of the longest diameters is ≥ 10 mm. Additional tumors are not exclusionary.
Adequate organ function as evidenced by:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10e9/L without G-CSF (filgrastim, pegfilgrastim, or equivalent) support within 7 days
- Hemoglobin (Hgb) ≥ 9.0 g/dL (90 g/L) without blood transfusion within 7 days
- Platelet count ≥ 100 x 10e9/L without platelet transfusion within 7 days
- Bilirubin ≤ 1.5 X upper limit of normal (ULN), except for patients with documented history of Gilbert's disease who may have DIRECT bilirubin ≤ 1.5 X ULN
- Alanine aminotransferase (ALT) ≤ 2.5 X ULN, except ≤ 5 X ULN for patients with liver metastases
- Aspartate aminotransferase (AST) ≤ 2.5 X ULN, except ≤ 5 X ULN for patients with liver metastases
- Serum creatinine ≤ 1.5 X ULN; or calculated creatinine clearance ≥ 50 mL/min (using Cockcroft-Gault formula), or measured creatinine clearance ≥ 50 mL/min.
Exclusion Criteria:
- Previous treatment with a camptothecin derivative (eg, irinotecan, topotecan, and investigational agents including but not limited to exatecan, rubitecan, gimatecan, karenitecin, SN38 investigational agents, EZN 2208, SN 2310, and AR 67) is not allowed
- Patients may not have a known history of leptomeningeal disease, as diagnosed by positive CSF cytology, unless prospective permission for enrollment is granted from the sponsor and the PI
- Patients may not have had major surgery or radiotherapy (therapeutic and/or palliative) within 14 days prior to initiation of study treatment, including CNS-directed radiation therapy. Minor procedures, such as tumor biopsy, thoracentesis, or intravenous catheter placement are allowed with no waiting period
Patients may not have the following co morbid disease or concurrent illness:
- Chronic or acute gastrointestinal (GI) disorders resulting in diarrhea of any severity grade; patients may not use chronic anti-diarrheal supportive care (more than 3 days/week) to control diarrhea in the 28 days prior to first dose of investigational drug. (exception: anti-diarrheal medications used to control symptoms from a medication that will be discontinued prior to study are allowed with a 7 day washout before study therapy, for example loperamide for erlotinib-associated diarrhea)
- Known cirrhosis, defined as Child Pugh class A or higher liver disease
- Other active malignancy, except for non melanoma skin cancer and carcinoma in situ (of the cervix or bladder)
- Any other severe/uncontrolled inter current illness or significant co morbid conditions that in the opinion of the investigator would impair study participation or cooperation
- Patients may not have a known allergy or hypersensitivity to any of the components of the investigational therapy, including polyethylene glycol (PEG) or topoisomerase inhibitors
Patients may not be receiving the following medications at the time of first dose of investigational drug:
- Pharmacotherapy for known hepatitis B or C, tuberculosis, or human immunodeficiency virus (HIV)
- Any of the following enzyme inducing anti epileptic medications (EIAEDs): phenytoin, carbamazepine, oxcarbazepine, phenobarbital
- Other chemotherapy, hormonal therapy, immunotherapy, other investigational agents, or biologic agents for the treatment of cancer except for bisphosphonates or denosumab
- Pregnant or nursing patients will be excluded from the study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort A - Pegylated Irinotecan to treat NSCLC
Patients with non-small cell lung carinoma (NSCLC) will receive pegylated irinotecan intravenously (IV) over 90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.
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Administered intravenously (IV) at 145 mg/m² as monotherapy once every 21 days (1 cycle)
Other Names:
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Experimental: Cohort B - Pegylated Irinotecan to treat SCLC
Patients with small cell lung carinoma (SCLC) will receive pegylated irinotecan intravenously (IV) over 90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.
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Administered intravenously (IV) at 145 mg/m² as monotherapy once every 21 days (1 cycle)
Other Names:
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Experimental: Cohort C - Pegylated Irinotecan to treat mBC
Patients with metastatic breast cancer (MBC) to brain will receive pegylated irinotecan intravenously (IV) over 90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.
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Administered intravenously (IV) at 145 mg/m² as monotherapy once every 21 days (1 cycle)
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Central Nervous System (CNS) Disease Control Rate (Cohort A and C)
Time Frame: At 12 weeks
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Central nervous system (CNS) disease control (DC) is defined as a complete response (CR); partial response (PR); or stable disease (SD). The outcome is reported as the number and percentage of participants who achieve DC, a number without dispersion. Response criteria are as follows. Note that any lesion less than 10 mm in longest diameter (LD) is considered unchanged unless there is a ≥ 3 mm change in the sum of the LDs.
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At 12 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Disease Control Rate (Cohort A and C)
Time Frame: At 12 weeks
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Overall disease control (DC) rate is defined as the sum in a cohort of the numbers of participants achieving complete response (CR); partial response (PR); or stable disease (SD), divided by the number of patients in that cohort. For this outcome, "overall" means all body systems, not just the central nervous system (CNS). The outcome is reported as DC rate, a number without dispersion. Response criteria are as follows. Note that any lesion <10 mm in longest diameter (LD) is considered unchanged unless there is a ≥3 mm change in the sum of the LDs.
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At 12 weeks
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Overall Response Rate (Cohort A and C)
Time Frame: At 12 weeks
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Overall response by subject (OR) is defined as the lower assessment between the central nervous system response and the systemic response. Response is defined as either complete response (CR) or partial response (PR). The outcome is reported as the number and percentage of participants who achieve OR, a number without dispersion. Response criteria are as follows. Note that any lesion < 10 mm in longest diameter (LD) is considered unchanged unless there is a ≥ 3 mm change in the sum of the LDs.
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At 12 weeks
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Systemic (Non-CNS) Disease Control Rate (Cohort A and C)
Time Frame: At 12 weeks
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Systemic (ie, non-central nervous system) disease control (DC) rate by cohort is defined as the number of patients with complete response (CR) + partial response (PR) + stable disease (SD), divided by the total number of patients. The outcome will be reported as DC rate, a number without dispersion. Response criteria are as follows. Note that any lesion < 10 mm in longest diameter (LD) is considered unchanged unless there is a ≥ 3 mm change in the sum of the LDs.
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At 12 weeks
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Systemic (Non-CNS) Response Rate (Cohort A and C)
Time Frame: At 12 weeks
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Systemic (ie, non-central nervous system) response rate by cohort is defined as the number of participants achieving a complete response (CR) or partial response (PR), divided by the number of participants. The outcome will be reported as a number without dispersion. Response criteria are as follows. Note that any lesion < 10 mm in longest diameter (LD) is considered unchanged unless there is a ≥ 3 mm change in the sum of the LDs.
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At 12 weeks
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Progression-free Survival (PFS) (Cohort A and C)
Time Frame: Date of first dose of pegylated irinotecan NKTR 102 to date of disease progression, assessed up to 2 years
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Progression-free survival (PFS) is defined as the time from the date of start of treatment until disease progression or death.
The outcome is reported by cohort as PFS in months, with full range.
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Date of first dose of pegylated irinotecan NKTR 102 to date of disease progression, assessed up to 2 years
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Overall Survival (Cohort A and C)
Time Frame: 4 years
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Overall survival (OS) is defined as the period remaining alive after the start of treatment.
The outcome is reported as the median with full range.
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4 years
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Central Nervous System (CNS) Disease Control (Cohort B)
Time Frame: At 12 weeks
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Central nervous system (CNS) disease control (DC) is defined as a complete response (CR); partial response (PR); or stable disease (SD). The outcome is reported as the number and percentage of participants who achieve DC, a number without dispersion. Response criteria are as follows. Note that any lesion less than 10 mm in longest diameter (LD) is considered unchanged unless there is a ≥ 3 mm change in the sum of the LDs.
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At 12 weeks
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Systemic Disease Control (Cohort B)
Time Frame: At 12 weeks
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Systemic (ie, non-central nervous system) disease control (DC) rate by cohort is defined as the number of patients with complete response (CR) + partial response (PR) + stable disease (SD), divided by the total number of patients. The outcome will be reported as DC rate, a number without dispersion. Response criteria are as follows. Note that any lesion < 10 mm in longest diameter (LD) is considered unchanged unless there is a ≥ 3 mm change in the sum of the LDs.
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At 12 weeks
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Related Adverse Events (Toxicity)
Time Frame: Up to 2 years
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Toxicity, defined as related adverse events, is reported as the total number of events experienced by the participants in each cohort, a number without dispersion.
Related is defined as meaning possibly, probably, or definitely related to the study drug.
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Up to 2 years
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Joel Neal, Stanford University Hospitals and Clinics
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Skin Diseases
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Disease Attributes
- Breast Diseases
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Breast Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Recurrence
- Small Cell Lung Carcinoma
- Brain Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Topoisomerase I Inhibitors
- Irinotecan
- Etirinotecan pegol
Other Study ID Numbers
- IRB-30982 (Other Identifier: Stanford University IRB)
- NCI-2014-02101 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- LUN0067 (Other Identifier: OnCore)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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