Advanced Breast CancerPhase 1/2POLTERNCT04826016
POL6326 (Balixafortide) Plus Nab-paclitaxel or Eribulin in Patients With HER2-negative Advanced Breast Cancer
A Phase 1/2 study testing POL6326, Eribulin and Nab paclitaxel in people with Advanced Breast Cancer, run by MedSIR.
Trial summary
This is a multicenter Phase Ib/II, open-label, dose-escalation study to optimize POL6326 (balixafortide) in combination with nab-paclitaxel or eribulin in patients with HER2-negative advanced breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Advanced Breast Cancer
- What is being tested?
- POL6326, Eribulin and Nab paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 16 Mar 2022to 16 Mar 2022
- Phase
- Phase 1/2
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female patients ≥18 years of age with histologically confirmed invasive breast cancer.
- Able to understand and willing to sign an IRB/IEC approved written informed consent document.
- Locally advanced stages IIIB/C or metastatic stage IV disease by American Joint Committee on Cancer (AJCC) criteria (8th edition).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy greater than 12 weeks.
- At least one measurable lesion per RECIST v.1.1 criteria.
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- Documented HER2-negative breast cancer in the advanced setting, with any ER and PgR status. HER2-negative (immunohistochemistry (IHC) 0, 1 or IHC 2+ and negative by in situ hybridization (ISH) test) status based on local testing on the most recent analyzed biopsy.
- Prior Therapies:
- For POL6326 (balixafortide)-eribulin combination
- phase Ib: At least 1 but no more than 3 prior chemotherapy-based lines of treatment for advanced or metastatic disease.
- phase 2: At least 1 but no more than 2 prior chemotherapy-based lines of treatment for advanced or metastatic disease.
- Prior therapy should have included an anthracycline and a taxane, unless contraindicated based on investigator's criteria. Chemotherapy line given as (neo)adjuvant treatment will be considered a prior line of therapy if disease progression occurred within 12-months after completion of prior (neo)adjuvant therapy.
- Note: for phase Ib and phase 2: Disease progression after last systemic therapy documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI). Exclusive tumor marker elevation will not be considered sufficient for diagnosis of disease progression.
- For POL6326 (balixafortide)-nab-paclitaxel combination
- phase Ib: At least 1 but no more than 2 prior chemotherapy-based lines of treatment for advanced or metastatic disease.
- phase 2: Up to 1 prior chemotherapy-based line of treatment for advanced or metastatic disease.
- For both combinations
- phase Ib: patients with HR+ status (ER+ and/or PgR+) must have been treated with at least one line of endocrine therapy (or considered by the treating physician not to be a candidate for endocrine therapy).
- phase 2: patients with HR+ status (ER+ and/or PgR+) must have been treated with at least one line of endocrine therapy and CDK4/6 inhibitors (unless contraindicated or not accessible).
- At least 21 days from the completion of any previous cytotoxic chemotherapy or biological therapy at time of initiation of POL6326 (balixafortide).
- Willingness and ability to provide a tumor biopsy from a newly obtained core or excisional biopsy not previously irradiated at the time of the inclusion and at the time of progression (optional) in order to perform exploratory studies. This enrolment criterium is optional for the dose-escalation part of the study, but mandatory for the final dose expansion (MTD/RP2D) cohorts. If this is not feasible (e.g., inaccessible tumor or subject safety concern), archival metastatic tumor samples might be acceptable after agreement with the Sponsor.
- Willingness and ability to provide blood samples for exploratory studies as per study protocol.
- Resolution of all acute toxic effects of prior anti-cancer therapy to grade 1 as determined by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v. 5.0 criteria (except for alopecia or other toxicities not considered a safety risk for the patient at Investigator's discretion).
- Adequate hematologic and organ function within 28 days before the first study treatment on Cycle 1 Day 1, defined by the following:
- Hematological: White blood cell (WBC) count > 3.0 x 109/L, absolute neutrophil count (ANC) > 1.5 x 109/L phase Ib of the study, platelet count > 100.0 x109/L, and hemoglobin > 9.0 g/dL.
- Hepatic: Serum albumin ≥ 3 g/dL; Total bilirubin ≤ 1.5 times the upper limit of normal (× ULN) (≤ 3 x ULN in the case of Gilbert's disease); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 × ULN (in the case of liver metastases ≤ 5 × ULN); alkaline phosphatase (ALP) ≤ 3.0 × ULN (≤ 5 × ULN in the case of liver and/or bone metastases).
- Renal: creatinine clearance ≥ 40 mL/min based on Cockcroft-Gault glomerular filtration rate estimation for POL6326 (balixafortide).
- Coagulation: International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless on medication known to alter INR and/or aPTT.
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods, or two effective contraceptive methods, as defined in the CSP during the treatment period and for at least 90 days after the last dose of study treatment, whichever is longer, and agreement to refrain from donating eggs during this same period. Women of childbearing potential must have a negative serum pregnancy test within 7 days before study treatment initiation
Who cannot join
- Patients will be excluded from the study if they meet ANY of the following criteria:
- Eribulin-based combination: patients have previously received eribulin.
- Peripheral neuropathy > Grade 1.
- Prior radiotherapy to only site of disease.
- Patients under concurrent local radiotherapy for pain control or life-threatening situations (e.g., spinal cord compression).
- Known active uncontrolled or symptomatic CNS metastases as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases are eligible if they have been definitively treated (e.g., radiotherapy, stereotactic surgery), and are clinically stable at least 4 weeks after completion of radiation therapy and/or surgery. Stable is defined as absence of new neurological symptoms, absence of need for dexamethasone or anticonvulsants, and radiographic confirmation of stable disease (SD). Radiographic confirmation of SD 4 weeks after completion of radiation therapy is not required unless indicated by neurological exam.
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- Presence of carcinomatous meningitis or leptomeningeal disease.
- Therapeutic radiation therapy within 14 days (seven days for limited-field palliative radiotherapy) prior to study enrollment, or patients who have not recovered from radiotherapy-related toxicities to grade ≤ 1.
- History of allergic reactions or known hypersensitivity attributed to compounds of similar chemical or biologic composition to POL6326 (balixafortide), eribulin or nab-paclitaxel, or to recombinant proteins, or any excipient contained in the drug formulation for POL6326 (balixafortide), eribulin or nab-paclitaxel.
- Breastfeeding or pregnancy as determined by a serum pregnancy test (β-HCG) at screening, prior to the administration of POL6326 (balixafortide) and/or eribulin and/or nab-paclitaxel. Since β-HCG over expression can be also elevated in some tumor types, a positive result should be confirmed with a validated alternative test (e.g., ultrasound).
- Note: Postmenopausal women must have been amenorrhoeic for ≥ 12 months in order to be considered "of non-childbearing potential". This should be documented appropriately in the patient's medical history. More frequent assessments may be performed if medically indicated as determined by the study site Investigator, and these evaluations should be recorded in the CRF (Case Report Form).
- Known HIV positivity on combination antiretroviral therapy.
- Congenital long QT syndrome (LQTS) with corrected QT interval using the Fridericia formula (QTcF) ≥ 480 ms on baseline EKG.
- Patients under treatment with drugs known to potentially prolong the QT interval, including class Ia and III anti-arrhythmic drugs will be either monitored for corrected QT (QTc) prolongation or excluded from participation in the trial, at the discretion of the treating physician.
- Aany other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment contraindicate patient participation in the clinical study.
- Severe concurrent psychiatric illness/social situation.
- Concurrent malignancy or malignancy within five years of study enrollment with the exception of carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I uterine cancer. For other cancers considered to have a low risk of recurrence, discussion with the Sponsor's Medical Monitor is required.
- Treatment with approved or investigational cancer therapy within 21 days prior to initiation of study.
- Concurrent participation in other clinical trial, except other translational studies.
About this study
Official title: A Phase Ib/II Study to Optimize POL6326 (Balixafortide) in Combination With Nab-paclitaxel or Eribulin in Patients With HER2-negative Advanced Breast Cancer
This is a multicenter Phase Ib/II, open-label, dose-escalation study to optimize POL6326 (balixafortide) in combination with nab-paclitaxel or eribulin in patients with HER2-negative advanced breast cancer.
- Conditions
- Advanced Breast Cancer
- Being tested
- POL6326, Eribulin, Nab paclitaxel
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
POL6326Drug
Also called Balixafortide
POL6326 (balixafortide): starting dose at 5.5 mg/Kg. Intravenous administration on day 1 and 8 of each 21-day cycle (+/- 1 day) (Phase Ib ARM A and Phase II ARM A ) or on day 1, 8 and 15 of each 28-day cycle (Phase Ib ARM B and Phase 2 ARM B) (+/- 1 day).
EribulinDrug
Also called Halaven
Eribulin: 1.23 mg/m2 (equivalent to 1.4 mg/m2 eribulin mesylate). Intravenous administration on day 1 and 8 of each 21-day cycle (+/- 1 day) (Phase Ib ARM A and Phase II ARM A ) or on day 1, 8 and 15 of each 28-day cycle (Phase Ib ARM B and Phase 2 ARM B) (+/- 1 day).
Nab paclitaxelDrug
Also called Abraxane
Nab-paclitaxel: 100 mg/m2. Intravenous administration on day 1 and 8 of each 21-day cycle (+/- 1 day) (Phase Ib ARM A and Phase II ARM A) or on day 1, 8 and 15 of each 28-day cycle (Phase Ib ARM B and Phase 2 ARM B) (+/- 1 day).
| Study group | Role | What they receive |
|---|---|---|
| PHASE Ib - ARM A: POL6326 (balixafortide) + eribulin | Experimental | On day 1 and 8 of each 21-day cycle (+/- 1 day) fixed eribulin dose of 1.23 mg/m2 (equivalent to 1.4 mg/m2 eribulin mesylate) combined with increasing doses of POL6326 (balixafortide) starting at a dose of 11 mg/Kg will be administered both intravenously. POL6326 (balixafortide) will be administered following a biphasic regimen (0,5 mg/Kg of POL6326 (balixafortide) dose during the first 30 min of treatment, the remaining dose during the following 3 h and 30 min for a total of 4h. Eribulin will be administered within 45 min after the end of the POL6326 (balixafortide) infusion over 2 to 5 min. Up to 4 additional cohorts may be introduced Receives: Drug: POL6326; Drug: Eribulin |
| PHASE Ib - ARM B: POL6326 (balixafortide) + nab-paclitaxel | Experimental | On day 1, 8 and 15 of each 28-day cycle (+/- 1 day) fixed nab-paclitaxel dose of 100 mg/m2 combined with increasing doses of POL6326 (balixafortide) starting at a dose of 5.5 mg/Kg will be administered both intravenously. POL6326 (balixafortide) will be administered following a biphasic regimen (0,5 mg/Kg of POL6326 (balixafortide) dose during the first 30 min of treatment, the remaining dose during the following 3 h and 30 min for a total of 4h. Nab-paclitaxel will be administered within 45 min after the end of the POL6326 (balixafortide) infusion over 30 min. Up to 5 additional cohorts may be introduced Receives: Drug: POL6326; Drug: Nab paclitaxel |
| PHASE 2 - ARM A: POL6326 (balixafortide) + eribulin | Experimental | MTD/RDP2 POL6326 (balixafortide) (from arm A phase Ib) will be administered over 4h intravenous infusion (biphasic regimen as detailed above/ phase Ib) followed by 1.4 mg/m2 eribulin over 5 min Intravenous infusion on days 1 and 8 in 21-day cycles (+/- 1 day). Receives: Drug: POL6326; Drug: Eribulin |
| PHASE 2 - ARM B: POL6326 (balixafortide) + nab-paclitaxel | Experimental | MTD/RDP2 POL6326 (balixafortide) (from arm B phase Ib) will be administered over 4h intravenous infusion (biphasic regimen as detailed above/ phase Ib) followed by 100 mg/m2 nab-paclitaxel over 30 min Intravenous infusion on days 1, 8 and 15 in 28-day cycles (+/- 1 day). Receives: Drug: POL6326; Drug: Nab paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
PHASE Ib: Maximum tolerated dose (MTD) / Recommended phase II dose (RP2D) of POL6326 (balixafortide)
MTD/RP2D, based on the incidence of Dose limiting toxicities (DLT) defined as the highest dose level explored at which up to one third of evaluable patients develop a DLT during the first treatment cycle.
Measured: 12 - 24 months
PHASE 2: Progression free survival (PFS)
To assess the efficacy of POL6326 (balixafortide) in combination with either eribulin or nab-paclitaxel in terms of PFS as per RECIST v. 1.1 in patients with HER2-negative ABC.
Measured: from treatment initiation until objective tumor progression or death (at least 4.5 months)
Secondary outcomes (23)
PHASE Ib: PFS
To assess the efficacy of POL6326 (balixafortide) in combination with either eribulin or nab-paclitaxel in terms of PFS as per RECIST v. 1.1 in patients with HER2-negative ABC.
Measured: from treatment initiation until objective tumor progression or death (at least 4.5 months)
PHASE Ib: Overall response rate (ORR)
To assess the preliminary efficacy of POL6326 (balixafortide) in combination with either eribulin or nab-paclitaxel in terms of ORR defined as the proportion of patients with complete response (CR) or partial response (PR) as per RECIST v.1.1
Measured: from baseline until end of study (will occur when all patients have discontinued treatment or 12 month after the last patient was enrolled on the study plus the safety follow up window of 28 days after last dose of study treatment in the last patient)
PHASE Ib: clinical benefit rate (CBR)
To assess the preliminary efficacy of POL6326 (balixafortide) in combination with either eribulin or nab-paclitaxel in terms of CBR, defined as the proportion of patients who obtain an objective response (CR or PR), or SD for at least 6 months for both combinations of the POL6326 (balixafortide) as per RECIST v.1.1.
Measured: at least 6 months
PHASE IB: duration of response (DoR)
To assess the preliminary efficacy of POL6326 (balixafortide) in combination with either eribulin or nab-paclitaxel in terms of DoR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, as per Investigator assessment using RECIST v.1.1.
Measured: from the first occurrence of a documented objective response to disease progression or death, up to 12 months
PHASE Ib: maximum tumor shrinkage (MTS)
To assess the preliminary efficacy of POL6326 (balixafortide) in combination with either eribulin or nab-paclitaxel in terms of MTS, from baseline in the size of target tumor lesions, defined as the biggest decrease, or smallest increase if no decrease observed, as per RECIST v.1.1.
Measured: from baseline until end of study (will occur when all patients have discontinued treatment or 12 month after the last patient was enrolled on the study plus the safety follow up window of 28 days after last dose of study treatment in the last patient
PHASE 2: ORR
To assess the efficacy, of POL6326 (balixafortide) in combination with either eribulin or nab-paclitaxel in terms of ORR, defined as the proportion of patients with CR or PR, as per RECIST v.1.1.
Measured: from baseline until end of study (will occur when all patients have discontinued treatment or 12 month after the last patient was enrolled on the study plus the safety follow up window of 28 days after last dose of study treatment in the last patient)
PHASE 2: CBR
To assess the efficacy, of POL6326 (balixafortide) in combination with either eribulin or nab-paclitaxel in terms of CBR, defined as the proportion of patients who obtain an objective response (CR or PR), or stable disease for at least 6 months for both combinations of the POL6326 (balixafortide) as per RECIST v.1.1.
Measured: at least 6 months
PHASE 2: time to response (TTR)
To assess the efficacy, of POL6326 (balixafortide) in combination with either eribulin or nab-paclitaxel in terms of TTR, defined as the time from treatment initiation to time of the first objective tumor response (tumor shrinkage of ≥ 30%) in patients who achieved a CR or PR, as per using RECIST v.1.1.
Measured: from treatment initiation to time of the first objective tumor response up to 12 months
PHASE 2: DoR
To assess the efficacy, of POL6326 (balixafortide) in combination with either eribulin or nab-paclitaxel in terms of DoR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, as per Investigator assessment using RECIST v.1.1.
Measured: from the first occurrence of a documented objective response to disease progression or death, up to 12 months
PHASE 2: overall survival (OS)
To assess the efficacy, of POL6326 (balixafortide) in combination with either eribulin or nab-paclitaxel in terms of OS, defined as the time from treatment initiation to death from any cause.
Measured: from baseline until end of study (will occur when all patients have discontinued treatment or 12 month after the last patient was enrolled on the study plus the safety follow up window of 28 days after last dose of study treatment in the last patient
PHASE 2: MTS
To assess the efficacy, of POL6326 (balixafortide) in combination with either eribulin or nab-paclitaxel in terms of MTS from baseline in the size of target tumor lesions, defined as the biggest decrease, or smallest increase if no decrease observed, as per RECIST v.1.1.
Measured: from baseline until end of study (will occur when all patients have discontinued treatment or 12 month after the last patient was enrolled on the study plus the safety follow up window of 28 days after last dose of study treatment in the last patient
PHASE Ib/ PHASE 2: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of POL6326 (balixafortide) in combination with either eribulin or nab-paclitaxel
Incidence and severity of AEs and SAEs according to the NCI-CTCAE v.5.0, including dose reductions, delays, and treatment discontinuations.
Measured: from baseline until end of study.All patients must be followed for AEs and SAEs for 28 days following the last dose of study drug
PHASE Ib - PHARMACOKINETICS (PK) in terms of area under the curve (AUC)
Plasma PK parameter AUC of POL6326 (balixafortide)
Measured: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE Ib - PK in terms of clearance (CL),
Plasma PK parameter CL of POL6326 (balixafortide)
Measured: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE Ib - PK in terms of distribution volume (Vd)
Plasma PK parameter Vd of POL6326 (balixafortide)
Measured: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE Ib - PK in terms of apparent half-life (t1/2)
Plasma PK parameter t1/2 of POL6326 (balixafortide)
Measured: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE Ib - PK in terms of maximal serum concentration (Cmax)
Plasma PK parameter Cmax of POL6326 (balixafortide)
Measured: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE Ib - PK in terms of trough concentrations (Ctrough)
Plasma PK parameter Ctrough of POL6326 (balixafortide)
Measured: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE Ib - PK in terms of time of maximum concentration observed (tmax)
Plasma PK parameter tmax of POL6326 (balixafortide)
Measured: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE Ib - PK in terms of time to last measurable plasma (tlast)
Plasma PK parameter tlast of POL6326 (balixafortide)
Measured: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE 2 - PK in terms of Cmax
Plasma PK parameter Cmax of POL6326 (balixafortide)
Measured: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE 2 - PK in terms of Cthrough
Plasma PK parameter Cthrough of POL6326 (balixafortide)
Measured: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE 2 - PK in terms of tmax
Plasma PK parameter tmax of POL6326 (balixafortide)
Measured: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2021
- Study start16 Mar 2022
- Primary completion16 Mar 2022
- Study completion16 Mar 2022
Why it stopped: Funder decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Breast CancerStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedSIR
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Javier Cortés, MD,PhD, Principal investigator, International Breast Cancer Center (IBCC), Quiron Group, Barcelona (Spain)Peter Kaufman, MD, Principal investigator, University of Vermont Medical Center, Burlington (Vermont, USA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04826016
- Sponsor's protocol ID
- MedOPP238
- Other IDs
- 2020-004203-13
- Acronym
- POLTER
- Status last verified
- Mar 2023
- First submitted
- 25 Mar 2021
- Last updated
- 20 Mar 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Study to Optimize POL6326 (Balixafortide) in Combination With Nab-paclitaxel or Eribulin in Patients With HER2-negative Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT04826016
- Acronym / sponsor ID
- POLTER / MedOPP238
- Conditions
- Advanced Breast Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funder decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- MedSIRUniversity, hospital or other
- Study start
- 16 Mar 2022 (actual)
- Primary completion
- 16 Mar 2022 (actual)
- Study completion
- 16 Mar 2022 (actual)
- First posted
- 1 Apr 2021 (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.
This is a multicenter Phase Ib/II, open-label, dose-escalation study to optimize POL6326 (balixafortide) in combination with nab-paclitaxel or eribulin in patients with HER2-negative advanced breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| PHASE Ib - ARM A: POL6326 (balixafortide) + eribulin | Experimental | Drug: POL6326, Drug: EribulinOn day 1 and 8 of each 21-day cycle (+/- 1 day) fixed eribulin dose of 1.23 mg/m2 (equivalent to 1.4 mg/m2 eribulin mesylate) combined with increasing doses of POL6326 (balixafortide) starting at a dose of 11 mg/Kg will be administered both intravenously. POL6326 (balixafortide) will be administered following a biphasic regimen (0,5 mg/Kg of POL6326 (balixafortide) dose during the first 30 min of treatment, the remaining dose during the following 3 h and 30 min for a total of 4h. Eribulin will be administered within 45 min after the end of the POL6326 (balixafortide) infusion over 2 to 5 min. Up to 4 additional cohorts may be introduced |
| PHASE Ib - ARM B: POL6326 (balixafortide) + nab-paclitaxel | Experimental | Drug: POL6326, Drug: Nab paclitaxelOn day 1, 8 and 15 of each 28-day cycle (+/- 1 day) fixed nab-paclitaxel dose of 100 mg/m2 combined with increasing doses of POL6326 (balixafortide) starting at a dose of 5.5 mg/Kg will be administered both intravenously. POL6326 (balixafortide) will be administered following a biphasic regimen (0,5 mg/Kg of POL6326 (balixafortide) dose during the first 30 min of treatment, the remaining dose during the following 3 h and 30 min for a total of 4h. Nab-paclitaxel will be administered within 45 min after the end of the POL6326 (balixafortide) infusion over 30 min. Up to 5 additional cohorts may be introduced |
| PHASE 2 - ARM A: POL6326 (balixafortide) + eribulin | Experimental | Drug: POL6326, Drug: EribulinMTD/RDP2 POL6326 (balixafortide) (from arm A phase Ib) will be administered over 4h intravenous infusion (biphasic regimen as detailed above/ phase Ib) followed by 1.4 mg/m2 eribulin over 5 min Intravenous infusion on days 1 and 8 in 21-day cycles (+/- 1 day). |
| PHASE 2 - ARM B: POL6326 (balixafortide) + nab-paclitaxel | Experimental | Drug: POL6326, Drug: Nab paclitaxelMTD/RDP2 POL6326 (balixafortide) (from arm B phase Ib) will be administered over 4h intravenous infusion (biphasic regimen as detailed above/ phase Ib) followed by 100 mg/m2 nab-paclitaxel over 30 min Intravenous infusion on days 1, 8 and 15 in 28-day cycles (+/- 1 day). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Female patients ≥18 years of age with histologically confirmed invasive breast cancer.
- Able to understand and willing to sign an IRB/IEC approved written informed consent document.
- Locally advanced stages IIIB/C or metastatic stage IV disease by American Joint Committee on Cancer (AJCC) criteria (8th edition).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy greater than 12 weeks.
Key exclusion criteria (19 listed)
- Eribulin-based combination: patients have previously received eribulin.
- Peripheral neuropathy > Grade 1.
- Prior radiotherapy to only site of disease.
- Patients under concurrent local radiotherapy for pain control or life-threatening situations (e.g., spinal cord compression).
- Known active uncontrolled or symptomatic CNS metastases as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases are eligible if they have been definitively treated (e.g., radiotherapy, stereotactic surgery), and are clinically stable at least 4 weeks after completion of radiation therapy and/or surgery. Stable is defined as absence of new neurological symptoms, absence of need for dexamethasone or anticonvulsants, and radiographic confirmation of stable disease (SD). Radiographic confirmation of SD 4 weeks after completion of radiation therapy is not required unless indicated by neurological exam.
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 |
|---|---|---|
| POL6326Also: BalixafortidePOL6326 (balixafortide): starting dose at 5.5 mg/Kg. Intravenous administration on day 1 and 8 of each 21-day cycle (+/- 1 day) (Phase Ib ARM A and Phase II ARM A ) or on day 1, 8 and 15 of each 28-day cycle (Phase Ib ARM B and Phase 2 ARM B) (+/- 1 day). | Drug | PHASE 2 - ARM A: POL6326 (balixafortide) + eribulin, PHASE 2 - ARM B: POL6326 (balixafortide) + nab-paclitaxel, PHASE Ib - ARM A: POL6326 (balixafortide) + eribulin, PHASE Ib - ARM B: POL6326 (balixafortide) + nab-paclitaxel |
| EribulinAlso: HalavenEribulin: 1.23 mg/m2 (equivalent to 1.4 mg/m2 eribulin mesylate). Intravenous administration on day 1 and 8 of each 21-day cycle (+/- 1 day) (Phase Ib ARM A and Phase II ARM A ) or on day 1, 8 and 15 of each 28-day cycle (Phase Ib ARM B and Phase 2 ARM B) (+/- 1 day). | Drug | PHASE 2 - ARM A: POL6326 (balixafortide) + eribulin, PHASE Ib - ARM A: POL6326 (balixafortide) + eribulin |
| Nab paclitaxelAlso: AbraxaneNab-paclitaxel: 100 mg/m2. Intravenous administration on day 1 and 8 of each 21-day cycle (+/- 1 day) (Phase Ib ARM A and Phase II ARM A) or on day 1, 8 and 15 of each 28-day cycle (Phase Ib ARM B and Phase 2 ARM B) (+/- 1 day). | Drug | PHASE 2 - ARM B: POL6326 (balixafortide) + nab-paclitaxel, PHASE Ib - ARM B: POL6326 (balixafortide) + nab-paclitaxel |
Primary outcome
PHASE Ib: Maximum tolerated dose (MTD) / Recommended phase II dose (RP2D) of POL6326 (balixafortide)
Time frame: 12 - 24 months
MTD/RP2D, based on the incidence of Dose limiting toxicities (DLT) defined as the highest dose level explored at which up to one third of evaluable patients develop a DLT during the first treatment cycle.
PHASE 2: Progression free survival (PFS)
Time frame: from treatment initiation until objective tumor progression or death (at least 4.5 months)
To assess the efficacy of POL6326 (balixafortide) in combination with either eribulin or nab-paclitaxel in terms of PFS as per RECIST v. 1.1 in patients with HER2-negative ABC.
23 secondary outcomes
PHASE Ib: PFS
Time frame: from treatment initiation until objective tumor progression or death (at least 4.5 months)
PHASE Ib: Overall response rate (ORR)
Time frame: from baseline until end of study (will occur when all patients have discontinued treatment or 12 month after the last patient was enrolled on the study plus the safety follow up window of 28 days after last dose of study treatment in the last patient)
PHASE Ib: clinical benefit rate (CBR)
Time frame: at least 6 months
PHASE IB: duration of response (DoR)
Time frame: from the first occurrence of a documented objective response to disease progression or death, up to 12 months
PHASE Ib: maximum tumor shrinkage (MTS)
Time frame: from baseline until end of study (will occur when all patients have discontinued treatment or 12 month after the last patient was enrolled on the study plus the safety follow up window of 28 days after last dose of study treatment in the last patient
PHASE 2: ORR
Time frame: from baseline until end of study (will occur when all patients have discontinued treatment or 12 month after the last patient was enrolled on the study plus the safety follow up window of 28 days after last dose of study treatment in the last patient)
PHASE 2: CBR
Time frame: at least 6 months
PHASE 2: time to response (TTR)
Time frame: from treatment initiation to time of the first objective tumor response up to 12 months
PHASE 2: DoR
Time frame: from the first occurrence of a documented objective response to disease progression or death, up to 12 months
PHASE 2: overall survival (OS)
Time frame: from baseline until end of study (will occur when all patients have discontinued treatment or 12 month after the last patient was enrolled on the study plus the safety follow up window of 28 days after last dose of study treatment in the last patient
PHASE 2: MTS
Time frame: from baseline until end of study (will occur when all patients have discontinued treatment or 12 month after the last patient was enrolled on the study plus the safety follow up window of 28 days after last dose of study treatment in the last patient
PHASE Ib/ PHASE 2: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of POL6326 (balixafortide) in combination with either eribulin or nab-paclitaxel
Time frame: from baseline until end of study.All patients must be followed for AEs and SAEs for 28 days following the last dose of study drug
PHASE Ib - PHARMACOKINETICS (PK) in terms of area under the curve (AUC)
Time frame: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE Ib - PK in terms of clearance (CL),
Time frame: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE Ib - PK in terms of distribution volume (Vd)
Time frame: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE Ib - PK in terms of apparent half-life (t1/2)
Time frame: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE Ib - PK in terms of maximal serum concentration (Cmax)
Time frame: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE Ib - PK in terms of trough concentrations (Ctrough)
Time frame: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE Ib - PK in terms of time of maximum concentration observed (tmax)
Time frame: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE Ib - PK in terms of time to last measurable plasma (tlast)
Time frame: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE 2 - PK in terms of Cmax
Time frame: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE 2 - PK in terms of Cthrough
Time frame: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
PHASE 2 - PK in terms of tmax
Time frame: At the end of Cycle 1 (each cycle is 28 days in POL6326 (balixafortide) - eribulin combination and 21 days in POL6326 (balixafortide) - nab paclitaxel combination)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2023.
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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 Cortés, MD,PhD principal investigator
International Breast Cancer Center (IBCC), Quiron Group, Barcelona (Spain)
Peter Kaufman, MD principal investigator
University of Vermont Medical Center, Burlington (Vermont, USA)
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing POL6326, Eribulin and Nab paclitaxel in people with Advanced Breast Cancer, run by MedSIR.
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 29 inclusion and 19 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: withdrawn, as of the sponsor's last update on 20 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 was withdrawn before enrolling participants, so there are no results.
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?
PHASE Ib: Maximum tolerated dose (MTD) / Recommended phase II dose (RP2D) of POL6326 (balixafortide) (time frame: 12 - 24 months). The study lists 2 primary outcomes in all. 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 20 Mar 2023; AzTrials last refreshed its copy on 7 Nov 2026.