Breast Cancer MetastaticPhase 2PhenomenalNCT03328884
Evaluation of the Efficacy and Safety of Nal-IRI for Progressing Brain Metastases in Breast Cancer Patients
A Phase 2 study testing Irinotecan (CPT-11) liposome in people with Breast Cancer Metastatic, run by MedSIR at 16 sites in Spain.
Trial summary
Multicenter open-label, phase II trial, to evaluate the efficacy and safety of nal-IRI in patients with HER2-negative breast cancer, who have documented Central Nervous System (CNS) progression following Whole Brain Radio Therapy (WBRT), Stereotactic Radiosurgery (SRS) and/or surgery, as determined by the Response… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer Metastatic
- What is being tested?
- Irinotecan (CPT-11) liposome
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 16 sitesSpain
- Study dates
- 2 May 2017to 2 Apr 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female or male patients > 18 years
- Patients must have a diagnosis of metastatic breast cancer.
- Patients should have been pretreated with taxanes at any time prior to the study enrolment if not formally contraindicated.
- At least one prior chemotherapy regimen for advanced disease.
- Evidence of new brain metastases and/or stable or progressive brain metastases following previous WBRT and/or SRS and/or surgery.
- At least one brain lesion needed to be measurable for new and progressive metastases (≥10 mm on T1-weighted, gadolinium-enhanced magnetic resonance imaging). For stable brain metastases at least one extracerebral lesion need to be measurable.
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- HER2 negative breast cancer defined as 0 - 1+ by immunohistochemistry or FISH negative result.
- ECOG performance status <2.
- Life expectancy >12 weeks.
- Patients must have sufficient organ and marrow function as defined below:
- Hematopoietic parameters: i. Absolute neutrophil count ≥ 1,5 x 109/L ii. Platelets ≥ 100 x 109/L iii. Haemoglobin ≥ 9 mg/dL b. Hepatic parameters: i. Total bilirubin ≤ 1.5 mg/dL ii. AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal c. Renal parameters: i. Creatinine ≤ 1.5 X institutional upper limits of normal, OR ii. Creatinine clearance ≥ 60 mL/min/1.73 m2 for pts w/ creatinine levels > institutional normal.
- Participants of childbearing potential must agree to use at least efficient contraception method (even though it is recommendable for them to use a highly effective method) prior to study entry and for the duration of study participation as well as a negative serum pregnancy test within 7 days of study enrolment and at the end of treatment visit.
- Ability to understand and the willingness to sign a written informed consent.
Who cannot join
- Patients must not have previously received nal-IRI or any other form of irinotecan, conventional or liposomal.
- Patients who have received prior anti-cancer treatment with chemotherapy, endocrine therapy, immunotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin-C) prior to starting study treatment.
- Radiation therapy encompassing more than 30% of bone marrow.
- Significant chronic gastrointestinal disorder with diarrhea as a major symptom (i.e Crohn's disease, ulcerative colitis, malabsorption, or grade ≥ 2 diarrhea of any etiology at baseline)
- Have a serious concomitant systemic disorder (e.g. active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator), previous history of bleeding diathesis, or treatment with Sintrom.
- Patients who have symptomatic lymphangitis, dyspnoea at rest or meningeal carcinomatosis. (Patients with asymptomatic involvement may be enrolled in the study.)
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- Patients must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy or other therapy intended for the treatment of breast cancer. For peripheral neuropathy, up to CTCAE (v4.0) Grade 2 is acceptable for patients with pre-existing condition.
- Patients may not be receiving any other investigational or anticancer agents while on the study.
- History of other malignancies, which could affect compliance with the protocol or interpretation of the results. Patients with malignancies diagnosed more than 5 years prior to study day 1, adequately treated carcinoma in situ of the cervix or basal or squamous cell skin are generally eligible.
- Pregnant or lactating women.
- NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure. Or known abnormal ECG with clinically significant abnormal findings.
- Active infection or an unexplained fever >38.5°C (excluding tumoral fever), which in the physician's opinion might compromise the patient's health.
- Patients with other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the study.
- Current use or any use in the last two weeks of strong CYP3A-enzyme inducers/inhibitors and/or strong UGT1A inhibitors
- Known hypersensitivity to any of the components of nanoliposomal irinotecan (nal-IRI) other liposomal irinotecan formulations or irinotecan.
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
Spain16 sites
ICO
Badalona
IOB Institute of Oncology - Quirón Barcelona
Barcelona
Hospital Universitario Virgen de Las Nieves
Granada, 18014
Hospital Universitario Clinico San Cecilio
Granada, 18016
H. Ruber Juan Bravo
Madrid
Hospital Clínico San Carlos
Madrid
Hospital Doce de Octubre
Madrid
Hospital Universitario Ramón y Cajal
Madrid
MD Anderson Madrid
Madrid
Hospital Clínico Virgen de la Victoria
Málaga
Hospital Universitari Son Espases
Palma de Mallorca
Son Llatzer
Palma de Mallorca
Sant Joan de Reus
Reus
Hospital Universitario Virgen del Rocío
Seville
IVO
Valencia
H. Miguel Servet
Zaragoza
About this study
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)
Multicenter open-label, phase II trial, to evaluate the efficacy and safety of nal-IRI in patients with HER2-negative breast cancer, who have documented Central Nervous System (CNS) progression following Whole Brain Radio Therapy (WBRT), Stereotactic Radiosurgery (SRS) and/or surgery, as determined by the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.
Read the detailed description
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).
- Conditions
- Breast Cancer Metastatic
- Being tested
- Irinotecan (CPT-11) liposome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Irinotecan (CPT-11) liposomeDrug
Also called nal-IRI
nal-IRI (nanoliposomal irinotecan, also known as MM-398 and PEP02) is irinotecan free base, (also known as CPT-11) a topoisomerase 1 inhibitor, encapsulated in a liposome drug delivery system.
nal-IRI will be administered 50 mg/m2 on D1 of a 14-day cycle in monotherapy.
| Study group | Role | What they receive |
|---|---|---|
| nal-IRI | Other | This is a single arm study. After signing the informed consent form, patients will start treatment with nal-IRI. nal-IRI will be administered 50 mg/m2 on D1 of a 14-day cycle in monotherapy. Receives: Drug: Irinotecan (CPT-11) liposome |
What is being measured
The primary outcome is the main question the study is designed to answer.
CNS Overall Response Rate (ORR)
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.
Measured: From Baseline up to 80 weeks after patient entry
Secondary outcomes (10)
CNS disease stabilization on week 12
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.
Measured: From Baseline up to 12 weeks after patient entry
ORR, according to a volumetric parameter, and to the RECIST v.1.1 criteria
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.
Measured: From Baseline up to 80 weeks after patient entry
CBR
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.
Measured: 3 years
Safety profile of nal-IRI in this population by Common Terminology Criteria for Adverse Events version 4 (CTCAE v.4) criteria
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.
Measured: 3 years
Progression-Free Survival (PFS)
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.
Measured: 3 years
Overall Survival (OS)
OS will be defined as the time from the first dose of treatment to death for any cause.
Measured: 3 years
Disease Control Rate
DCR will be defined as the percentage of patients who experience a CR, PR or stable disease determined locally by the investigator, using RANO-BM criteria (for IC lesions) and RECIST criteria v.1.1 (for IC, EC, and overall lesions) in patients with progressing brain metastases and in all patients with CNS involvement.
Measured: 18 months after last patient included
TTR
TTR will be defined as the time from treatment initiation to time of the first objective tumor response observed in patients who achieved a CR or PR, determined locally by the investigator, using RANO-BM criteria (for IC lesions) and RECIST criteria v.1.1 (for IC, EC, and overall lesions) in patients with progressing brain metastases and in all patients with CNS involvement.
Measured: From treatment initiation to time of the first objective tumor response in patients with CR or PR,
DoR
DoR will be defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, determined locally by the investigator, using RANO-BM criteria (for IC lesions) and RECIST criteria v.1.1 (for IC, EC, and overall lesions) in patients with progressing brain metastases and in all patients with CNS involvement.
Measured: time from the first occurrence of a documented objective response to disease progression or death
MTS
MTS from baseline in the size of target tumor lesions, defined as the biggest decrease, or smallest increase if no decrease observed, determined locally by the investigator, using RANO-BM criteria (for IC lesions) and RECIST criteria v.1.1 (for IC, EC, and overall lesions) in patients with progressing brain metastases and in all patients with CNS involvement.
Measured: From baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2017
- Study start2 May 2017
- Primary completion31 Aug 2018
- Study completion2 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Cancer MetastaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is an international, prospective, open-label, multicenter, single arm, two-stage Simon Design phase II clinical trial
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedSIR
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Javier Cortes, Principal investigator, Hospital Universitario Ramon y Cajal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03328884
- Sponsor's protocol ID
- MedOPP107
- Other IDs
- 2016-002689-30, 2016
- Acronym
- Phenomenal
- Status last verified
- Apr 2025
- First submitted
- 17 Mar 2017
- Last updated
- 23 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: It is not planned
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03328884
- Acronym / sponsor ID
- Phenomenal / MedOPP107
- Conditions
- Breast Cancer Metastatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- MedSIRUniversity, hospital or other
- Study start
- 2 May 2017 (actual)
- Primary completion
- 31 Aug 2018 (actual)
- Study completion
- 2 Apr 2025 (actual)
- First posted
- 1 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multicenter open-label, phase II trial, to evaluate the efficacy and safety of nal-IRI in patients with HER2-negative breast cancer, who have documented Central Nervous System (CNS) progression following Whole Brain Radio Therapy (WBRT), Stereotactic Radiosurgery (SRS) and/or surgery, as determined by the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is an international, prospective, open-label, multicenter, single arm, two-stage Simon Design phase II clinical trial
| Arm | Type | Receives |
|---|---|---|
| nal-IRI | Other | Drug: Irinotecan (CPT-11) liposomeThis is a single arm study. After signing the informed consent form, patients will start treatment with nal-IRI. nal-IRI will be administered 50 mg/m2 on D1 of a 14-day cycle in monotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Female or male patients > 18 years
- Patients must have a diagnosis of metastatic breast cancer.
- Patients should have been pretreated with taxanes at any time prior to the study enrolment if not formally contraindicated.
- At least one prior chemotherapy regimen for advanced disease.
- Evidence of new brain metastases and/or stable or progressive brain metastases following previous WBRT and/or SRS and/or surgery.
Key exclusion criteria (15 listed)
- Patients must not have previously received nal-IRI or any other form of irinotecan, conventional or liposomal.
- Patients who have received prior anti-cancer treatment with chemotherapy, endocrine therapy, immunotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin-C) prior to starting study treatment.
- Radiation therapy encompassing more than 30% of bone marrow.
- Significant chronic gastrointestinal disorder with diarrhea as a major symptom (i.e Crohn's disease, ulcerative colitis, malabsorption, or grade ≥ 2 diarrhea of any etiology at baseline)
- Have a serious concomitant systemic disorder (e.g. active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator), previous history of bleeding diathesis, or treatment with Sintrom.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Irinotecan (CPT-11) liposomeAlso: nal-IRInal-IRI (nanoliposomal irinotecan, also known as MM-398 and PEP02) is irinotecan free base, (also known as CPT-11) a topoisomerase 1 inhibitor, encapsulated in a liposome drug delivery system. nal-IRI will be administered 50 mg/m2 on D1 of a 14-day cycle in monotherapy. | Drug | nal-IRI |
Primary outcome
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.
10 secondary outcomes
CNS disease stabilization on week 12
Time frame: From Baseline up to 12 weeks after patient entry
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
CBR
Time frame: 3 years
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
Progression-Free Survival (PFS)
Time frame: 3 years
Overall Survival (OS)
Time frame: 3 years
Disease Control Rate
Time frame: 18 months after last patient included
TTR
Time frame: From treatment initiation to time of the first objective tumor response in patients with CR or PR,
DoR
Time frame: time from the first occurrence of a documented objective response to disease progression or death
MTS
Time frame: From baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2025.
- Individual participant dataSharing planned: No. It is not planned
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Javier Cortes principal investigator
Hospital Universitario Ramon y Cajal
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Irinotecan (CPT-11) liposome in people with Breast Cancer Metastatic, run by MedSIR at 16 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CNS Overall Response Rate (ORR) (time frame: From Baseline up to 80 weeks after patient entry). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2025.