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Breast Cancer Stage IVPhase 1/22019-101826NCT04896320

Tucatinib With Chemotherapy and Trastuzumab in Advanced Her-2-neu Overexpressing, Previously Treated Breast Cancer.

A Phase 1/2 study testing Tucatinib in people with Breast Cancer Stage IV, run by Providence Health & Services at 4 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is an open label study of tucatinib in combination with either vinorelbine or gemcitabine and trastuzumab in patients with metastatic HER2+ breast cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer Stage IV
What is being tested?
Tucatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
4 sitesUnited States
Study dates
15 Dec 2021to 19 Jun 2023
Phase
Phase 1/2
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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age >18, with metastatic breast cancer, documented Her2+ by FISH/Dual-ISH, and/or IHC 3+ staining, local determination of Her2+ allowed
  • Progressive disease with history of prior treatment with trastuzumab and capecitabine for metastatic disease (unless deemed intolerable or ineligible for capecitabine by the investigator).
  • Prior treatment with T-DM1 in any setting unless deemed intolerable or ineligible for T-DM1 by the investigator.
  • Target or non-target lesions per RECIST 1.1.
  • ECOG 0 or 1.
  • In the opinion of the investigator, life expectancy >6 months.
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  • LVEF > 50% by ECHO or MUGA within 4 weeks prior to first study treatment.
  • Cr Clearance > 50mL/min per institutional guidelines.
  • Negative serum pregnancy test for women of child bearing potential within 14 days of first study treatment and must agree to use effective contraception through 30 days after last treatment.
  • For subjects who can father children:
  • Must agree not to donate sperm starting at time of informed consent and continuing throughout the study period and for at least 30 days after the final study drug administration.
  • If sexually active with a person of childbearing potential in a way that could lead to pregnancy, must consistently use a barrier method of birth control starting at time of informed consent and continuing throughout the study and for at least 30 days after the final dose of study drug administration.
  • If sexually active with a person who is pregnant or breastfeeding, must consistently use a barrier method of birth control starting at time of informed consent and continuing throughout the study and for at least 30 days after the final dose of study drug administration.
  • Willing and able to provide written Informed consent.
  • All toxicities related to prior cancer therapies must have resolved to < grade 1, with following exceptions: alopecia, neuropathy, which must have resolved to <Grade 2; congestive heart failure which must have been <grade 1 in severity at the time of occurrence and resolved completely.
  • Adequate hematologic and hepatic function as defined by:
  • Hemoglobin >9g/dL
  • Absolute neutrophil count (ANC)>1000 cells/uL
  • Platelets >100,000/uL
  • Total bilirubin < 1.5 X upper limit of normal (ULN), except for subjects with known Gilbert's disease, who may enroll if the conjugated bilirubin is < 1.5 X ULN
  • Transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase [AST/SGOT] and alanine aminotransferase/serum glutamic pyruvic transaminase [ALT/SGPT]) ≤ 2.5 X ULN (≤ 5 X ULN if liver metastases are present)
  • CNS Inclusion - Based on screening contrast brain MRI, patients must have one of the following:
  • No evidence of brain metastases
  • Untreated brain metastases not needing immediate local therapy. For patients with untreated CNS lesions > 2.0 cm on screening contrast brain MRI, discussion with and approval from the medical monitor is required prior to enrollment
  • Previously treated brain metastases
  • Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy in the opinion of the investigator.
  • 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 enroll if all of the following criteria are met:
  • Time since WBRT is ≥ 21 days prior to first dose of treatment, time since 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

Who cannot join

  • Having previous treatment with vinorelbine and gemcitabine for metastatic disease.
  • History of allergic reactions to trastuzumab except for grade 1/2 infusion reactions.
  • History of allergic reactions to tucatinib.
  • Any systemic anti-cancer therapy <14 days of first study treatment, including any experimental agents.
  • Clinically significant cardiopulmonary disease including ventricular arrhythmia requiring therapy
  • Uncontrolled hypertension (defined as persistent systolic blood pressure > 150mmHG and/or diastolic blood pressure >100mm Hg on antihypertensive medication) or any history of symptomatic CHF
Show all 18Show fewer
  • Known history of HIV, Hep B/C or known chronic liver disease.
  • Known MI or unstable angina in last 6 months prior to first study treatment
  • Inability to swallow pills or significant GI disease, in the opinion of the Investigator that would preclude oral absorption of the medication.
  • Are pregnant, breastfeeding, or planning pregnancy.
  • 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 enrollment is given.
  • Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of > 2 mg of dexamethasone (or equivalent). However, patients on a chronic stable dose of ≤ 2 mg total daily of dexamethasone (or equivalent) may be eligible with discussion and approval by the medical monitor.
  • Any brain lesion thought to require immediate local therapy, including (but not limited to) a lesion in an anatomic site where increase in size or possible treatment-related edema may pose risk to patient (e.g. brain stem lesions). 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.
  • Known or suspected LMD as documented by the investigator. E. Have poorly controlled (> 7days) generalized or complex partial seizures, or manifest neurologic progression due to brain metastases notwithstanding CNS-directed therapy
  • Use of a strong CYP3A4 or CYP2C8 inhibitor within ≤14days, or use of a strong CYP3A4 or CYP2C8 inducer within ≤5 days prior to the first study treatment. CYP3A4 or CYP2C8 inducers and inhibitors are also prohibited as concomitant medications within ≤14 days of initiating Tucatinib treatment. . Use of sensitive CYP3A substrates should be avoided two weeks before enrollment and during study treatment. See Appendices C, D, E for references. (See Section 7.6 for additional prohibited concomitant medications)
  • Prior radiation therapy less than 7 days from start of treatment.
  • Other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Providence Cancer Institute - Clackamas Clinic

    Clackamas, Oregon, 97015

  • Providence Newberg Medical Center

    Newberg, Oregon, 97132

  • Portland Providence Medical Center

    Portland, Oregon, 97213

  • Providence St. Vincent Medical Center

    Portland, Oregon, 97225

Other trials in United States

About this study

Official title: A Phase 1/2 Study of Tucatinib With Chemotherapy and Trastuzumab in Patients With Previously Treated, Advanced Her-2-Neu Overexpressing Breast Cancer.

This is an open label study of tucatinib in combination with either vinorelbine or gemcitabine and trastuzumab in patients with metastatic HER2+ breast cancer.

Read the detailed description

This phase I/II study will assess the recommended dosing of tucatinib in combination with trastuzumab and either vinorelbine or gemcitabine in patients with advanced, HER2+ breast cancer. The study will be conducted as a parallel cohort study looking at optimal dose and safety and efficacy.

Arm 1 Gemcitabine + Tucatinib + Trastuzumab: Gemcitabine (1000 mg/m2) will be administered intravenously on Days 1 and 8. The investigational study drug (tucatinib) will be administered as 300mg by mouth taken twice a day of every day in each cycle. Trastuzumab will be administered per package insert on Day 1 of each cycle.

Arm 2 Vinorelbine + Tucatinib + Trastuzumab: Vinorelbine (25 mg/m2) will be administered intravenously on Days 1 and 8 of each cycle. The investigational study drug (tucatinib) will be administered as 300mg by mouth twice a day of every day in each cycle. Trastuzumab will be administered per package insert on Day 1 of each 2 cycle.

Note: Cycle length is 21 days.

Being tested
Tucatinib
Keywords
Metastatic, Her2+, Trastuzumab, Tucatinib
Medical subject headings
Breast Neoplasms, Neoplasm Metastasis

What participants receive

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

  • TucatinibDrug

    Tucatinib is a highly selective, oral, reversibly Her2 small molecule tyrosine kinase inhibitor (TKI).

Study groups in NCT04896320
Study groupRoleWhat they receive
Gemcitabine + Tucatinib + TrastuzumabExperimentalGemcitabine (1000 mg/m2) will be administered intravenously on Days 1 and 8 of each 21-day cycle. The investigational study drug (tucatinib) will be administered as 300mg by mouth taken twice a day of every day in each cycle. Trastuzumab will be administered per package insert on Day 1 of each cycle.
Receives: Drug: Tucatinib
Vinorelbine + Tucatinib + TrastuzumabExperimentalVinorelbine (25 mg/m2) will be administered intravenously on Days 1 and 8 of each 21-day cycle. The investigational study drug (tucatinib) will be administered as 300mg by mouth taken twice a day of every day in each cycle. Trastuzumab will be administered per package insert on Day 1 of each cycle.
Receives: Drug: Tucatinib

What is being measured

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

  1. To determine the maximum tolerated dose and recommended dosing of tucatinib to be given in combination with either vinorelbine or gemcitabine and trastuzumab.

    Measured: Cycle 1 Day 1 (each cycle is 21 days) to 30 Day Safety Follow-Up (after treatment), approximately 14 weeks

Secondary outcomes (3)

  1. Study Treatment-Related Adverse Events

    Number of participants given tucatinib in combination with vinorelbine or gemcitabine with trastuzumab with treatment-related adverse events as assessed by CTCAE v5.0 with Her-2-neu overexpressing metastatic breast cancer.

    Measured: Cycle 1 Day 1 (each cycle is 21 days) to 30 Day Safety Follow-Up, approximately 14 weeks

  2. Overall Response Rate

    Number of patients who have a partial or complete response to treatment per RECIST 1.1.

    Measured: Up to 5 Years

  3. Progression Free Survival

    Length of time from start of study treatment to disease progression or death from any cause.

    Measured: Up to 5 Years

Timeline

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

  1. First posted21 May 2021
  2. Study start15 Dec 2021
  3. Primary completion19 Jun 2023
  4. Study completion19 Jun 2023

Why it stopped: Study will be closed due to zero enrollment.

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04896320
Sponsor's protocol ID
2021000247
Acronym
2019-101826
Status last verified
Jun 2023
First submitted
10 May 2021
Last updated
22 Jun 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tucatinib in people with Breast Cancer Stage IV, run by Providence Health & Services at 4 sites in United States.

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 28 inclusion and 18 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: withdrawn, as of the sponsor's last update on 22 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 withdrawn before enrolling participants, so there are no results.

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?

To determine the maximum tolerated dose and recommended dosing of tucatinib to be given in combination with either vinorelbine or gemcitabine and trastuzumab. (time frame: Cycle 1 Day 1 (each cycle is 21 days) to 30 Day Safety Follow-Up (after treatment), approximately 14 weeks). 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 NCT04896320.

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 22 Jun 2023.

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