Evaluation of the Efficacy and Safety of Nal-IRI for Progressing Brain Metastases in Breast Cancer Patients (Phenomenal)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03328884|
Recruitment Status : Recruiting
First Posted : November 1, 2017
Last Update Posted : April 18, 2019
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer Metastatic||Drug: Irinotecan Hydrochloride||Phase 2|
This is an international, prospective, open-label, multicenter, single arm, two-stage Simon Design phase II clinical trial, with the primary objective of assessing the efficacy of nal-IRI single agent in a cohort of HER2-negative metastatic breast cancer (MBC) patients with CNS involvement.
Eligible patients will have histologically proven diagnosis of adenocarcinoma of the breast, they must have progressed to at least one prior chemotherapy regimen in the metastatic setting and must have been progressed in CNS to previous local treatment (Surgery and/or WBRT and/or SRS) showing at least one measurable lesion in the CNS (symptomatic meningeal carcinomatosis is not permitted). Eligible patients must have been previously received at least treatment with taxanes (either in the neo/adjuvant or in the metastatic scenario). Patients could not be eligible if they are candidates for a local treatment with a radical intention.
Patients will be accrued in a two-stage design. Considering a drop-out rate of 10%, the accrual goal will be a total of 63 patients in both stages (first stage will include 23 evaluable patients and the second stage will include 33 more evaluable patients).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||63 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||This is an international, prospective, open-label, multicenter, single arm, two-stage Simon Design phase II clinical trial|
|Masking:||None (Open Label)|
|Official Title:||Multicenter Open-label, Phase II Trial, to Evaluate the Efficacy and Safety of Nal-IRI for Progressing Brain Metastases in Patients With HER2-negative Breast Cancer (The Phenomenal Study)|
|Actual Study Start Date :||May 2, 2017|
|Estimated Primary Completion Date :||October 15, 2022|
|Estimated Study Completion Date :||February 20, 2023|
This is a single arm study. After signing the informed consent form, patients will start treatment with nal-IRI. nal-IRI will be administered at a fixed dose of 60 mg/m2 on D1 of a 14-day cycle in monotherapy.
Drug: Irinotecan Hydrochloride
nal-IRI (nanoliposomal irinotecan, also known as MM-398 and PEP02) is irinotecan hydrochloride, (also known as CPT-11) a topoisomerase 1 inhibitor, encapsulated in a liposome drug delivery system.
nal-IRI will be administered with a fixed dose of 60 mg/m2 on D1 of a 14-day cycle in monotherapy.
- CNS Overall Response Rate (ORR) [ Time Frame: From Baseline up to 80 weeks after patient entry ]The efficacy of nal-IRI will be measured in terms of CNS ORR, defined as per RANO-BM criteria. According to these criteria Complete Response (CR) will be defined as the disappearance of all CNS target lesions sustained for at least 4 weeks; no new lesions, no corticosteroids; stable or improved clinically. Partial Response (PR) will be defined as a decrease of at least 30% in the sum longest diameter (LD) of CNS target lesions, taking as reference the baseline sum LD, sustained for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically.
- CNS disease stabilization on week 12 [ Time Frame: From Baseline up to 12 weeks after patient entry ]CNS clinical benefit rate (CBR) at week 12 will be defined as the percentage of patients who experience a CR, PR or Stable Disease (SD) for at least 12 weeks assessed by the modified Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v.1.1) criteria.
- ORR, according to a volumetric parameter, and to the RECIST v.1.1 criteria [ Time Frame: From Baseline up to 80 weeks after patient entry ]ORR according to a volumetric parameter. For this objective, PR will be defined as > 65% volumetric reduction of CNS lesion(s) and to the RECIST v.1.1 criteria. The volumetric parameter will be centrally reviewed.
- CBR [ Time Frame: 3 years ]The percentage of patients who experience a CR, PR or SD for at least 24 weeks and assessed by the RECIST v.1.1 criteria.
- Safety profile of nal-IRI in this population by Common Terminology Criteria for Adverse Events version 4 (CTCAE v.4) criteria [ Time Frame: 3 years ]This study will consider the National Cancer Institute (NCI) CTCAE v.4 criteria grade 3 and 4 adverse events (AEs) and serious AEs (SAEs) in order to assess the safety and tolerability objectives.
- Progression-Free Survival (PFS) [ Time Frame: 3 years ]PFS will be defined as the time from the first dose of treatment to death or disease progression as assessed by the Investigator per RECIST v1.1 criteria.
- Overall Survival (OS) [ Time Frame: 3 years ]OS will be defined as the time from the first dose of treatment to death for any cause.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03328884
|Contact: Cristina Masferrerfirstname.lastname@example.org|
|Contact: Alicia Garciaemail@example.com|
|Barcelona, Spain, 08023|
|Contact +34932214135 firstname.lastname@example.org|
|Principal Investigator:||Javier Cortes||Hospital Universitario Ramon y Cajal|