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Advanced Breast CancerPhase 2CAILANCT04714619

CB-103 Plus NSAI In Luminal Advanced Breast Cancer

A Phase 2 study testing CB-103 in people with Advanced Breast Cancer, run by MedSIR at 2 sites in Spain.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Multicenter, single-arm, open label, phase II clinical trial with safety run-in to evaluate the safety, tolerability, pharmacokinetics and efficacy of CB-103 in combination with a non-steroidal aromatase inhibitor (NSAI), anastrozole or letrozole, in Hormone Receptor-positive and Human Epidermal Growth Factor Receptor… 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?
CB-103
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
2 sitesSpain
Study dates
6 May 2021to 26 Apr 2022
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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must meet ALL of the following inclusion criteria to be eligible for enrolment into the study:
  • Signed the informed consent form (ICF) prior to any study-related activities.
  • Female patients ≥ 18 years of age at time of ICF signature.
  • Pre- or peri-menopausal women being treated with a LHRH analogue for at least 28 days prior to study entry (if shorter, post-menopausal levels of serum estradiol/Follicle-stimulating hormone [FSH] must be confirmed analytically), or post-menopausal women as defined by any of the following criteria:
  • Age ≥60 years;
  • Age <60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and serum estradiol and/or FSH level within the laboratory's reference range for postmenopausal females;
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  • Documented bilateral oophorectomy.
  • Eastern Cooperative Oncology Group (ECOG) performance status lower or equal to 1.
  • Life expectancy greater or equal to 6 months.
  • Locally advanced or metastatic breast cancer not amenable to treatment with curative intend.
  • Histologically confirmed ER-positive and/or PgR-positive (with ≥10% positive stained cells according to National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines) and HER2-negative (0-1+ by immunohistochemistry [IHC] or 2+ and negative by in situ hybridization [ISH] test) breast cancer based on local testing on the most recent analyzed biopsy.
  • Patients with radiological evidence (as per RECIST v.1.1) of disease progression on the immediate prior line of treatment containing a non-steroidal aromatase inhibitor (NSAI) (anastrozole-letrozole). Patients must meet at least one of the following conditions:
  • On adjuvant endocrine therapy for ≥ 24 months and relapsing within 12 months after CDK4/6 inhibitor treatment completion following the adjuvant setting.
  • Progression to an NSAI in the advanced setting (with or without a CDK4/6 inhibitor) after obtaining clinical benefit (stable disease for ≥ 6 months, CR or PR) Note: Last dose of NSAI (anastrozole or letrozole) of the prior ET must have been received within the 28 days before starting study treatment.
  • At least 1 and no more than 3 prior lines of endocrine therapy for ABC, including the treatment received at the time of study entry. ET might have been combined with targeted agents such as everolimus, PI3K inhibitors, CDK4/6 inhibitors, etc.
  • Evidence of measurable or non-measurable disease according to RECIST v.1.1. Patients with only bone lesions are not eligible.
  • Note: Previously irradiated lesions can be considered as measurable disease only if disease progression has been unequivocally documented at that site since radiation.
  • Willingness and ability to provide tumor biopsy at study entry (available tumor tissue sample from a fresh pre-treatment core or excisional biopsies).
  • In the case of biopsable lesions that can be safely accessed, the patient should also consent to a biopsy at the time of start of Cycle 2 (C2D1 ± 3 days), unless investigator considers there are any medical concerns. These cases will be discussed with Sponsor medical monitor on a case by case basis.
  • At disease progression, a tumor biopsy will be requested if there are accessible lesions.
  • If available, patients will be asked to provide archived primary or metastatic tumor specimen, but consent will not be limiting for enrolment.
  • Patients agree to collection of blood samples for molecular analysis.
  • Adequate hematological and organ function within 14 days before the first CB 103 dose:
  • Hematological (without platelet transfusion or granulocyte colony-stimulating factor [G-CSF] support within 14 days before first CB 103 dose): i. White blood cell (WBC) count > 3.0 x 109/L; ii. Absolute neutrophil count (ANC) > 1.5 x 109/L; iii. Platelet count > 75.0 x109/L; iv. Hemoglobin > 10.0 g/dL. b. Hepatic: i. Serum albumin ≥ 3 g/dL; ii. Total bilirubin ≤ 1.5 times the upper limit of normal (× ULN) (< 3 x ULN in the case of Gilbert's disease); iii. Aspartate transaminase (AST), and alanine transaminase (ALT) ≤ 3.0 times × ULN (in the case of liver metastases ≤ 5 × ULN); iv. Alkaline phosphatase (ALP) ≤ 2.5 times × ULN (≤ 5 × ULN in the case of liver and/or bone metastases ≤ 5 × ULN).
  • Renal: i. Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 30 mL/min based on Cockcroft-Gault glomerular filtration rate estimation.
  • Coagulation: i. Partial thromboplastin time (PTT) ≤ 1.5 x ULN (or activated Partial Thromboplastin Time [aPTT]) and international normalized ratio (INR) ≤ 1.5 times × ULN.
  • Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  • Women of childbearing potential must have a negative serum pregnancy test within 7 days before start of study treatment. These women must agree to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods, or two effective contraceptive methods (as defined in the protocol) during the treatment period and for at least 90 days after the last dose of CB 103, and agreement to refrain from donating eggs during this same period.
  • 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 (except for alopecia or other toxicities, such as myelosuppression, not violating other inclusion criteria and not considered a safety risk for the patient at investigator's discretion).

Who cannot join

  • Patients will be excluded from the study if they meet ANY of the following criteria:
  • Prior chemotherapy and/or Notch signaling inhibitors treatment (e.g., gamma-secretase inhibitors) in the metastatic setting.
  • Treatment with any approved or investigational cancer therapy between the end of NSAI treatment and study entry.
  • Rapidly or symptomatic progressive visceral disease or any disease burden that contraindicates continuing ET according to Investigator's judgement.
  • Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated (e.g., radiotherapy, stereotactic surgery) and are neurologically stable off anticonvulsants and steroids for at least 4 weeks before start of treatment.
  • Receiving any of following concomitant medications that cannot be discontinued during the study treatment duration (see Section 6.9 and 6.10 for more details):
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  • Drugs which prolong QT interval, either with a known or a conditional/ possible risk to induce Torsades de Pointes (listed in Appendix 3).
  • Coumarin-type anticoagulants (such as warfarin) within one week prior first CB 103 dose. Low molecular weight heparin and direct oral anticoagulants are permitted.
  • Current or prior malignancy within 5 years prior to study enrolment, except non-melanoma skin cancer, or carcinoma in situ of the uterine cervix. Patients with other cancers considered to have a low risk of recurrence might be included after approval by the Medical Monitor.
  • Radiotherapy or limited-field palliative radiotherapy within 7 days prior to enrolment or patients not having recovered from radiotherapy-related toxicities to baseline or Grade ≤ 1 and/or from whom ≥ 25% of the bone marrow has been previously irradiated.
  • Inability to swallow capsules or tablets.
  • Impairment of gastrointestinal function or presence of gastrointestinal disease that may significantly alter the absorption of CB-103.
  • Impaired cardiac function or clinically significant cardiac disease, including any of the following:
  • Clinically significant cardiac disease including congestive heart failure (New York Heart Association [NYHA] class III or IV), arrhythmia or conduction abnormality requiring medication, or cardiomyopathy
  • Clinically uncontrolled hypertension (systolic blood pressure > 160 or diastolic blood pressure >110 mmHg).
  • Complete left bundle branch block.
  • Right bundle branch block and left anterior hemiblock
  • Mandatory use of a cardiac pacemaker.
  • Congenital long QT syndrome.
  • History or presence of sustained or symptomatic ventricular tachyarrhythmia.
  • Presence of atrial fibrillation.
  • Clinically significant resting bradycardia (< 50 bpm).
  • Corrected QT interval using Fridericia formula (QTcF) > 470 ms at the Screening ECG.
  • QRS ≥ 110 ms.
  • History of symptomatic congestive heart failure.
  • Left ventricular ejection fraction (LVEF) < 50%. History of absolute decrease in LVEF of ≥ 15 absolute percentage points, or ≥ 10 absolute percentage points and crossing from > lower limits of normal (LLN) to < LLN on anticancer therapy, even if asymptomatic.
  • Angina pectoris ≤ 6 months prior to first CB 103 dose.
  • Acute myocardial infarction (MI) ≤ 6 months prior to starting study drug.
  • General conditions or other clinically significant diseases, including any one of the following:
  • Hemorrhagic, embolic, or thrombotic stroke within 6 months prior to the first CB-103 dose
  • Prior allogeneic bone marrow/hematopoietic stem cell transplant
  • Prior autologous hematopoietic stem cell transplant for breast cancer (for other indications within ≤ 6 months prior first CB 103 dose.
  • Known infection with human immunodeficiency virus (HIV) or hepatitis B or C requiring treatment.
  • Any active infection requiring the use of parenteral anti-microbial agents or that is > Grade 2.
  • Non-malignant interstitial lung disease or pneumonitis.
  • Dyspnea of any cause requiring supplemental oxygen therapy and dyspnea at rest due to complications of advanced malignancy and co-morbidities.
  • Significant traumatic injury or major surgery (i.e., opening of a body cavity, e.g., thoracotomy, laparotomy, laparoscopic organ resection) or major orthopedic procedures (e.g. joint replacement, open reduction and internal fixation) within 14 days prior first CB-103 dose.
  • Other concurrent severe and/or uncontrolled medical conditions (e.g. uncontrolled diabetes, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol.
  • Hypersensitivity to CB-103 or any of its excipients.
  • Pregnant or breast-feeding patients.

Trial locations and contacts

2 sites in 1 country.

Spain2 sites

  • Complejo Hospitalario de Jaen

    Jaén

  • Hospital Sant Joan de Reus

    Reus

Other trials in Spain

About this study

Official title: CB-103 Plus NSAI In Luminal Advanced Breast Cancer: CAILA Study

Multicenter, single-arm, open label, phase II clinical trial with safety run-in to evaluate the safety, tolerability, pharmacokinetics and efficacy of CB-103 in combination with a non-steroidal aromatase inhibitor (NSAI), anastrozole or letrozole, in Hormone Receptor-positive and Human Epidermal Growth Factor Receptor 2 (HER2)-negative advanced breast cancer patients who have achieved clinical benefit during prior NSAI-based treatment.

Read the detailed description

This is a ulticenter, single arm, open-label, Phase II clinical trial to evaluate the safety, tolerability, pharmacokinetics, and efficacy of CB-103 in combination with a non-steroidal aromatase inhibitor (NSAI), anastrozole or letrozole, in Hormone Receptor-positive and Human Epidermal Growth Factor Receptor 2 (HER2)-negative advanced breast cancer patients who have achieved clinical benefit during prior NSAI-based treatment.

Eligible patients include pre- and post-menopausal women age ≥ 18 years with HR-positive and HER2-negative unresectable advanced breast cancer (ABC, including metastatic), having achieved at least clinical benefit upon treatment with prior NSAI. Evidence of measurable or evaluable disease, as per RECIST (Response Evaluation Criteria In Solid Tumors) v.1.1, with a tumor lesion amenable to biopsy. Pre-menopausal women must be under treatment with luteinizing hormone-releasing hormone (LHRH) analogues. Patients are not eligible if they are candidates for a local treatment with a curative intention

The primary objective is to assess the efficacy, defined as progression-free survival (PFS), of CB-103 in combination with NSAI therapy (anastrozole or letrozole) in women with HR-positive, HER2-negative, unresectable ABC with evidence of Notch signaling pathway activation and with progressive disease after clinical benefit while on prior NSAI-containing regimen.

Approx 80 patients are expected to be recruited

Being tested
CB-103

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CB-103Drug

    Also called Letrozole, Anastrozole

    Patients will receive CB-103 capsules orally (QD) in combination with NSAI therapy (letrozole or anastrozole, continuing prior therapy) also orally once daily, and based on a 28-day treatment cycle.

    A run-in phase for safety and tolerability of CB-103 in combination with anastrozole or letrozole will be conducted as an initial step of the phase II trial to confirm the safe dose of CB-103 in combination with NSAI given at standard dose.

    Patients will receive treatment until disease progression (as defined by RECIST v.1.1), symptomatic deterioration, unacceptable toxicity, death, consent withdrawal or study termination, whichever occurs first.

Study groups in NCT04714619
Study groupRoleWhat they receive
CB-103 + NSAI therapyExperimentalHormone Receptor (HR)-positive and HER2-negative advanced breast cancer, including metastatic (ABC).Approximately 80 patients
Receives: Drug: CB-103

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival (PFS)

    PFS, defined as the time from treatment initiation until objective tumor progression or death from any cause, whichever occurs first, as per Investigator assessment by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 in the subgroup of patients with evidence of Notch signaling pathway activation.We hypothesize that excluding a median PFS of 2 months while targeting an improvement of the median PFS greater than or equal to 4 months (hr = 0.50) in patients with evidence of Notch pathway activation is an optimal approach to evaluate the clinical activity of the CB-103 plus NSAI (anastrozole or letrozole) combination.

    Measured: from treatment initiation until objective tumor progression or death

Secondary outcomes (14)

  1. Safety and tolerability of CB-103 in combination with NSAI (anastrozole or letrozole)

    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.

  2. Efficacy in terms of PFS of CB-103 in combination with NSAI in all patients and in sub.groups

    PFS, defined as the time from treatment initiation until objective tumor progression or death from any cause, whichever occurs first, as per Investigator assessment by RECIST v.1.1 in all patients and in patients without evidence of Notch signaling pathway activation.

    Measured: from treatment initiation until objective tumor progression or death (at least 4months)

  3. Overall response rate (ORR)

    ORR, defined as the proportion of patients with complete response (CR) or partial response (PR), as per Investigator assessment using RECIST v.1.1., in patients with and without evidence of Notch signalling pathway activation.

    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)

  4. Clinical benefit rate (CBR)

    CBR at 24 weeks, defined as the proportion of patients who obtain an objective response (CR or PR), or stable disease for at least 24 weeks, as per Investigator assessment using RECIST v.1.1., in patients with or without evidence of Notch signaling pathway activation.

    Measured: 24 weeks

  5. Clinical benefit rate (CBR)

    CBR at 12 weeks, defined as the proportion of patients who obtain an objective response (CR or PR), or stable disease for at least 12 weeks, as per Investigator assessment using RECIST v.1.1., in patients with or without evidence of Notch signaling pathway activation.

    Measured: 12 weeks

  6. Time to tumor response (TTR)

    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 Investigator assessment using RECIST v.1.1., in patients with or without evidence of Notch signaling pathway activation.

    Measured: from treatment initiation to time of the first objective tumor response up to 12 months

  7. Duration of response (DoR)

    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., in patients with or without evidence of Notch signaling pathway activation.

    Measured: from the first occurrence of a documented objective response to disease progression or death, up to 12 months

  8. Overall survival (OS)

    OS, defined as the time from treatment initiation to death from any cause, in patients with or without evidence of Notch signaling pathway activation.

    Measured: from baseline until end of study

  9. Maximum tumor shrinkage (MTS)

    MTS from baseline in the size of target tumor lesions, defined as the biggest decrease, or smallest increase if no decrease observed, as per Investigator assessment using 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)

  10. Pharmacokinetics (PK), in terms of Cmax

    Plasma PK parameters (Cmax) of CB-103, anastrozole and letrozole.

    Measured: from baseline until end of treatment, an average of 12 months

  11. PK, in terms of AUC

    Plasma PK parameters (Area under the plasma concentration versus time curve (AUC of CB-103, anastrozole and letrozole.

    Measured: from baseline until end of treatment, an average of 12 months

  12. PK in terms of Vd/F

    Plasma PK parameters (Vd/F ) of CB-103, anastrozole and letrozole.

    Measured: from baseline until end of treatment, an average of 12 months

  13. PK in terms of CL/F

    Plasma PK parameters (CL/F ) of CB-103, anastrozole and letrozole.

    Measured: from baseline until end of treatment, an average of 12 months

  14. Pharmacokinetics (PK), in terms of Tmax

    Plasma PK parameters Tmax of CB-103, anastrozole and letrozole.

    Measured: from baseline until end of treatment, an average of 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jan 2021
  2. Study start6 May 2021
  3. Primary completion2 Sep 2021
  4. Study completion26 Apr 2022

Why it stopped: Sponsor decision

Resources

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
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04714619
Sponsor's protocol ID
MedOPP319
Acronym
CAILA
Status last verified
Jun 2022
First submitted
2 Dec 2020
Last updated
19 Dec 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CB-103 in people with Advanced Breast Cancer, run by MedSIR at 2 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 29 inclusion and 40 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: stopped early, as of the sponsor's last update on 19 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 was stopped early (reason given: Sponsor decision). Results are not available in the source record.

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?

Progression-free survival (PFS) (time frame: from treatment initiation until objective tumor progression or death). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04714619.

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 19 Dec 2023.

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