A clinical trial comparing tucatinib against placebo in patients who have advanced breast cancer and are being treated with capecitabine and trastuzamab

Phase 1

Active, not recruiting

• Conditions: Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Carcinoma; MedDRA version: 23.0Level: PTClassification code 10065430Term: HER2 positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-002801-12-IT
• Lead Sponsor: CASCADIAN THERAPEUTICS INC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-06-18
• Last Update Posted: 19 April 2022

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 480

Inclusion Criteria

Have histologically confirmed HER2+ breast carcinoma, with HER2+ defined by fluorescence in situ hybridization (FISH) and/or 3+ staining by immunohistochemistry (IHC)
Have received previous treatment with a taxane, trastuzumab, pertuzumab, and T-DM1
Have progression of unresectable locally advanced or metastatic breast cancer after last systemic therapy (as confirmed by investigator), or be
intolerant of last systemic therapy Have measurable or non-measureable disease assessable by RECIST 1.1
At least 18 years of age at time of consent Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1
Have adequate hepatic function
Have adequate baseline hematological parameters
Have creatinine clearance = 50 mL/min
Have left ventricular ejection fraction (LVEF) = 50%
If female of childbearing potential, must have a negative result of serum pregnancy test.
Women of childbearing potential and men with partners of childbearing potential must agree to use a highly effective birth control methods.
CNS Inclusion – Based on screening brain magnetic resonance imaging (MRI), patients must have one of the following:
- No evidence of brain metastases
- Untreated brain metastases not needing immediate local therapy.
- Previously treated brain metastases
a. Brain metastases previously treated with local therapy my either be stable since treatment or may have progressed since prior local CNS therapy.
b. Patients treated with CNS local therapy for newly identified lesions found on initial MRI performed during screening for this study may be eligible to enrol if all of the following criteria are met:
i. Time since whole brain radiation therapy (WBRT) is > 21 days prior to first dose of treatment, time since stereotactic radiosurgery (SRS) is > 7 days prior to first dose of treatment, or time since surgical resection is > 28 days
ii. Other sites of evaluable disease are present
c. Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 451
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 29

Exclusion Criteria

Have previously been treated with:
a. lapatinib within 12 months of starting study treatment or
b. neratinib, afatinib, or other investigational HER2/epidermal growth factor receptor (EGFR) or HER2 tyrosine kinase inhibitor (TKI) at any time previously.
Have previously been treated with capecitabine for metastatic disease.
Note patients who have received capecitabine for adjuvant or neoadjuvant treatment at least 12 months prior to starting study treatment are eligible.
Have any toxicity related to prior cancer therapies that has not resolved to = Grade 1
Have clinically significant cardiac disease
Are known carriers of Hepatitis B or Hepatitis C or have other known chronic liver disease
Are known to be positive for human immunodeficiency virus (HIV)
Require therapy with warfarin or other coumarin derviatives
Unable for any reason to undergo MRI of the brain
CNS Exclusion – Based on screening brain MRI, patients must not have any of the following:
Any untreated brain metastases > 2.0 cm in size unless discussed with medical monitor and approval for enrolment is given
Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total dose of > 2mg dexamethasone.
Any lesion thought to require immediate local therapy. Patients who undergo local treatment for such lesions identified by screening MRI may
still be eligible for the study based on criteria described under CNS inclusion criteria 20b
Known or concurrent leptomeningeal disease (LMD)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified