Clinical Study of Local and Systemic Biological Impact of GLP1/GIP-Receptor Agonists in Patients With Breast Cancer: The CLARA Trial

NCT07676331 | Not Yet Recruiting Phase 2 FDA Drug

• 2 other identifiers: S717362026-525820-76
• Study Type: interventional
• Target: 168
• Locations: 0 countries
• Sites: N/A

Brief Summary

The CLARA trial is a phase II window-of-opportunity trial evaluating how a commonly used weight-loss medication (tirzepatide, a GLP-1/GIP receptor agonist) affects breast cancer biology, alone and in combination with standard hormone therapy (letrozole). The main goal is to determine whether tirzepatide, alone or combined with letrozole, reduces tumor cell growth.

Conditions

Hormone-receptor-positive Breast Cancer; Early Breast Cancer

Keywords

GLP-1/GIP receptor agonist; tirzepatide; letrozole; Window-of-opportunity trial; Weight-loss drugs

Outcome Measures

Primary Outcomes (1)

• Ki67 proliferation marker

  The primary endpoint is the mean change in log-transformed KI67 expression values between baseline and time of surgery in the different arms

  From enrollment till time of surgery (4-5 weeks)

Secondary Outcomes (5)

• Adherence

  From enrollment till time of surgery

• Adverse Event profile

  From enrollment till 3 weeks postoperative

• Perioperative complications

  From time of surgery up till 3 weeks postoperative

• ctDNA presence

  From enrollment till 3 weeks postoperative

• ctDNA changes

  From enrollment till 3 weeks postoperative

Other Outcomes (8)

• Fatigue

  From enrollment up till 3 weeks postoperative

• Body composition changes

  From enrollment up till 3 weeks postoperative

• Change in genomic risk score

  From enrollment till time of surgery (4-5 weeks)

Study Arms (4)

Arm A (Control): Immediate surgery

NO INTERVENTION

Patient undergoes immediate surgery without intervention

Arm B: letrozole

ACTIVE COMPARATOR

3 weeks of neoadjuvant letrozole 2.5 mg/d

Drug: Letrozole (Aromatase Inhibitors)

Arm C: tirzepatide

ACTIVE COMPARATOR

3 weeks of neoadjuvant tirzepatide. Cycle 1: 2.5 mg/w Cycle 2: 5 mg/w Cycle 3: 5 mg/w

Drug: Tirzepatide

Arm D: letrozole + tirzepatide

ACTIVE COMPARATOR

3 weeks of neoadjuvant letrozole 2.5mg/d and tirzepatide: * Cycle 1: 2.5mg/w * Cycle 2: 5mg/w * Cycle 3: 5mg/w

Drug: Tirzepatide; Drug: Letrozole (Aromatase Inhibitors)

Interventions

Tirzepatide DRUG

Tirzepatide is a GIP and GLP-1R agonist. It is approved by FDA and EMA as a weight-loss drug for patients with BMI ≥30 kg/m2 or ≥27 kg/m2 and previously diagnosed with at least 1 weight-related comorbidity.

Arm C: tirzepatide; Arm D: letrozole + tirzepatide

Letrozole (Aromatase Inhibitors) DRUG

Letrozole is an nonsteroidal aromatase inhibitor (NSAI). It is an adjuvant endocrine treatment indicated for HR+ breast cancer.

Arm B: letrozole; Arm D: letrozole + tirzepatide

Eligibility Criteria

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

You may qualify if:

• Voluntary written informed consent of the participant has been obtained prior to any screening procedures
• Patient is \>18 years of age
• Patient is postmenopausal, as defined per local practice
• Tumour size of ≥1 cm
• The patient has a biopsy-confirmed diagnosis of GII-III ER+, HER2 - early stage breast cancer scheduled for primary surgery as per standard-of-care
• To fulfil the requirement for HR+ disease by local testing on primary disease specimen, tumour must be ER positive defined by immunohistochemistry (IHC) according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for hormone receptor testing.
• To fulfil the requirement of HER2- disease by local testing on primary disease specimen, tumour must be HER2- according to ASCO/CAP guidelines for HER2 testing
• All histological subtypes are eligible, including but not limited to invasive breast cancer of no special type (IBC-NST) , invasive lobular carcinoma (ILC) etc.
• Have a BMI of
• ≥30 kg/m2 or
• ≥27 kg/m2 and previously diagnosed with at least 1 of the following weight-related comorbidities:
• i. Hypertension: treated or with systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg ii. Dyslipidaemia: treated or with LDL ≥160 mg/dL (4.1 mmol/L) or triglycerides ≥150 mg/dL (1.7 mmol/L), or HDL iii. Obstructive sleep apnoea iv. Cardiovascular disease, for example, ischemic cardiovascular disease, New York Heart Association Functional Classification Class I-III heart failure
• Patient should be able to read/understand Dutch, French or English
• Willing to commit to the study program and comply with all related protocol procedures
• Willing to undergo a new biopsy of the breast lesion in case no formalin-fixed paraffin-embedded (FFPE) block can be made available for the trial.

You may not qualify if:

• Have Type 1 or 2 diabetes mellitus, history of ketoacidosis, or hyperosmolar state or coma.
• Have at least 1 laboratory value suggestive of diabetes during screening : HbA1c ≥6.5% (≥48 mmol/mol) or fasting glucose ≥126 mg/dL (≥7.0 mmol/L)
• Have a history of BC exceptions are made for:
• Contralateral in situ BC without systemic treatment
• Ipsilateral in situ BC without systemic treatment or radiation therapy
• Have a history of an additional invasive malignancy that is progressing or that has required active treatment in the 3 years prior to breast cancer diagnosis. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Are receiving or has received within 3 months prior to screening systemic glucocorticoid therapy (excluding topical, intraocular, intranasal, intra-articular, or inhaled preparations) or have evidence of a significant, active autoimmune that has required (within the last 3 months) or is likely to require, in the opinion of the investigator, concurrent treatment with systemic treatment (such as glucocorticoids (excluding topical, intraocular, intranasal, intra-articular, or inhaled preparations)) during the course of the study.
• Have a history of any other condition, such as known drug or alcohol abuse, diagnosed eating disorder, or other psychiatric disorder, that, in the opinion of the investigator, may preclude the participant from following and completing the protocol
• Family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2)
• Have a self-reported change in body weight \>5 kg within 3 months prior to screening
• Have a prior surgical treatment for obesity, excluding liposuction or abdominoplasty
• Have endoscopic and/or device-based therapy for obesity or have had device removal within the last 6 months prior to screening
• Have renal impairment measured as eGFR \<30L/min/1.73m2
• Have a known clinically significant gastric emptying abnormality (for example, severe gastroparesis or gastric outlet obstruction) or chronically take drugs that directly affect GI motility
• Have a history of chronic or acute pancreatitis

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• King Baudouin Foundation: collaborator
• KU Leuven: collaborator

Related Publications (1)

• 1. Dindo et al, 2004, Ann Surg

  BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Tirzepatide; Letrozole; Aromatase Inhibitors

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs

Study Officials

• Patrick Neven, MD, PhD

  Universitaire Ziekenhuizen KU Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christine Desmedt, PhD

CONTACT

+3216321194; christine.desmedt@kuleuven.be

Josephine Van Cauwenberge, MD

CONTACT

+3216321194; josephine.vancauwenberge@kuleuven.be

Study Design

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

Model Details: Window-of-Opportunity trial

Study Record Dates

• First Submitted: June 16, 2026
• First Posted: June 30, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: July 7, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share