CB-103 Plus NSAI In Luminal Advanced Breast Cancer

NCT04714619 | Terminated Phase 2 DMC

• 1 other identifier: MedOPP319
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

Brief 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 2 (HER2)-negative advanced breast cancer patients who have achieved clinical benefit during prior NSAI-based treatment.

Conditions

Advanced Breast Cancer

Outcome Measures

Primary Outcomes (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.

  from treatment initiation until objective tumor progression or death

Secondary Outcomes (14)

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

  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.

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

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

• Overall response rate (ORR)

  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)

• Clinical benefit rate (CBR)

  24 weeks

• Clinical benefit rate (CBR)

  12 weeks

Study Arms (1)

CB-103 + NSAI therapy

EXPERIMENTAL

Hormone Receptor (HR)-positive and HER2-negative advanced breast cancer, including metastatic (ABC).Approximately 80 patients

Drug: CB-103

Interventions

CB-103 DRUG

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.

Also known as: Letrozole, Anastrozole

CB-103 + NSAI therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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):
• 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).

Sponsors & Collaborators

• MedSIR: lead
• Cellestia Biotech AG: collaborator

Study Sites (2)

Complejo Hospitalario de Jaen

Jaén, Spain

Location

Hospital Sant Joan de Reus

Reus, Spain

Location

MeSH Terms

Interventions

Letrozole; Anastrozole

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Antonio Llombart-Cussac

  Arnau de Vilanova Hospital, Valencia (Spain)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2020
• First Posted: January 19, 2021
• Study Start: May 6, 2021
• Primary Completion: September 2, 2021
• Study Completion: April 26, 2022
• Last Updated: December 19, 2023

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2)