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

Phase 1

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-AT

Lead Sponsor: Seagen Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 600

Inclusion Criteria

Double-Blinded Phase:
Have histologically confirmed HER2+ breast carcinoma, with HER2+ defined by in situ hybridization (ISH) or fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) methodology

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 hematologic parameters

Have creatinine clearance = 50 mL/min or, in patients = 45 kg in weight, a serum creatinine within institutional normal limits

Have left ventricular ejection fraction (LVEF) = 50%

If female of childbearing potential, must have a negative result of serum or urine 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 contrast 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 contrast brain 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 disease assessable by RECIST 1.1 are present
c. Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions

Unblinded Phase:
For patients who were randomized to the control arm and on the longterm follow-up period at the time of the crossover screening: 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-measurable disease assessable by RECIST 1.1

Have ECOG PS 0 or 1

Adequate hepatic function

Adequate hematologic parameters

Have creatinine clearance = 50 mL/min as calculated per institutional guidelines or, in patients = 45 kg in weight, serum creatinine within institutional normal limits

Have LVEF = 50% as assessed by ECHO or MUGA scan documented within 6 weeks prior to the time of crossover consent

If female of childbearing potential, must have a negative result of serum or urine pregnancy test.

Women of childbearing potential and men with partners of childbearing potential must agree to use a highly effective birth control methods

Exclusion Criteria

Double-Blinded Phase:
Have previously been treated with:
a. lapatinib within 12 months of starting study treatment (except in cases where lapatinib was given for = 21 days and was discontinued for reasons other than disease progression or severe toxicity)
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 (or other fluoropyrimidine [e.g., 5-fluorouracil]) for metastatic disease (except in cases where capecitabine was given for = 21 days and was discontinued for reasons other than disease progression or severe toxicity). Note patients who have received capecitabine for adjuvant or neoadjuvant treatment at least 12 months prior to starting study treatment are eligible.

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 cardiopulmonary 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 lesions > 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 brain lesion thought to require immediate local therapy. Patients who undergo local treatment for such lesions identified by screening contrast brain MRI may still be eligible for the study based on criteria described under CNS inclusion criteria 19b

Known or suspected leptomeningeal disease (LMD)

Unblinded Phase:
Discontinuation of study treatment due to an adverse event while on the double-blind phase of the study

Have any toxicity related to prior cancer therapies that has not resolved to = Grade 1

Have clinically significant cardiopulmonary disease

Are known carriers of Hepatitis B or Hepatitis C or have other known chronic liver disease

Are known to be positive for HIV

Require therapy with warfarin or other coumarin derivatives

Unable for any reason to undergo contrast MRI of the brain

CNS Exclusion – Based on crossover screening brain MRI, patients must not have any of the following:
Any untreated brain lesions > 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.

Known or suspected leptomeningeal disease (LMD)

Have poorly controlled (> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to brain metastases notwithstanding CNS-directed therapy

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Related Trials