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HER2-positive Breast CancerPhase 2TUC-TOCNCT05955170

Tucatinib in Combination With Oral Etoposide andTrastuzumab in Patients With Metastatic HER2+ Breast Cancer

A Phase 2 study testing Tucatinib in Combination of Oral VP16 and trastuzumab in people with HER2-positive Breast Cancer, run by Institut Curie at 13 sites in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This is an open-label, multicenter, phase II study to evaluate the efficacy, safety, tolerability, pharmacokinetics of the combination of tucatinib-Oral VP16-trastuzumab in patients with HER2-positive metastatic breast cancer (HER2+ MBC) after progression on tucatinib-capecitabine-trastuzumab or capecitabine-related… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HER2-positive Breast Cancer
What is being tested?
Tucatinib in Combination of Oral VP16 and trastuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
13 sitesFrance
Study dates
19 Dec 2023to 19 Dec 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • First disease progression under tucatinib-capecitabine-trastuzumab. OR Medical contra-indication to initiate or continue capecitabine in association with tucatinib-trastuzumab (investigator's decision based on patient medical history, DPD deficiency and/or capecitabine grade 2 toxicity or higher).
  • Age > 18 years,
  • Histologically confirmed HER2+ breast carcinoma (ASCO/CAP guidelines) with archived tumor tissue available,
  • Have a life expectancy of at least 3 months,
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1,
  • Participants must be able to swallow capsules,
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  • Participants must be able and willing to be available for the duration of the study and are willing to follow study procedures,
  • Measurable disease, assessed by RECIST version 1,
  • Patients with brain metastases are eligible:
  • Unless urgent treatment is required
  • If 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
  • Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions
  • Left ventricular ejection fraction (LVEF) ≥ 50% (within 4 weeks before inclusion)
  • Adequate organ function (obtained within 14 days prior to treatment start) as evidenced by:
  • o Absolute neutrophil count (ANC) ≥ 1.5 X 10^9/L
  • o Hemoglobin (Hgb) ≥ 9 g/dL
  • o Platelet count ≥ 100 X 10^9/L
  • Bilirubin ≤ 1.5 X upper limit of normal (ULN), except for patients with a documented history of Gilbert's disease (≤ 2 X ULN)
  • Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 2.5 X ULN (for patients with liver metastases ≤ 5 X ULN);
  • Alkaline phosphatase (AP) ≤ 3 X ULN (for patients with liver metastases, ≤ 5 X ULN);
  • Serum creatinine ≤ 1.5 mg/dL (133 μmol/L) or calculated creatinine clearance ≥ 50 mL/min (using Cockcroft-Gault formula).
  • If the patient is female:
  • Women of childbearing potential (WCBP): negative serum pregnancy test. The patient must be willing to use effective methods of contraception. Patients must be postmenopausal, surgically infertile, or willing to use a physical barrier method of contraception in addition to an intrauterine device or hormonal contraception until at least 6 months after completion of study treatment,
  • If the patient is male:
  • Male patients must agree to use an acceptable method of contraception (e.g., condom) during the study and for 3 months after completion of investigational treatment, 14. Patients must be covered by a health insurance plan. 15. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Who cannot join

  • Have previously been treated with:
  • 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/ EGFR or HER2 TKI at any time previously (excepted for patients already under tucatinib who continue without interruption).
  • Patients who are pre-treated with tucatinib and who received a decreased dose of tucatinib (<300mg twice daily) are not eligible in the safety run-in phase.
  • Have used a strong CYP3A4 or CYP2C8 inhibitor within 5 half-lives of the inhibitor, or have used a strong CYP3A4 or CYP2C8 inducer within 5 days prior to first dose of study treatment (see Appendix 4 and 5)
  • Patients unable for any reason to undergo MRI of the brain.
  • Leptomeningeal metastases or brain metastases requiring immediate symptomatic treatment or a high dose of corticosteroid therapy (≥2mg/day dexamethasone or equivalent).
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  • Have poorly controlled (> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to brain metastases notwithstanding CNS-directed therapy
  • Any toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1 at time of treatment start, with the following exceptions:
  • Alopecia and neuropathy (must have resolved to ≤ Grade 2)
  • Congestive Heart Failure (must have been ≤ Grade 1 in severity at the time of occurrence and must have resolved completely)
  • Anemia (must have resolved to ≤ Grade 2)
  • Patients who have had a last dose of IV chemotherapy within 21 days, last dose of oral cytotoxic chemotherapy, radiotherapy, biological therapy, or investigational therapy within 14 days prior to treatment start. This does not apply to patients already under tucatinib who continue without interruption.
  • Patients who have had any major surgery within 28 days prior to inclusion.
  • Have evidence within 2 years of the start of study treatment of another malignancy that required systemic treatment. This does not apply to patients already under tucatinib who continue without interruption.
  • Concomitant use of other agents for the treatment of cancer or any investigational agent(s).
  • Women who are either pregnant, lactating, planning to get pregnant
  • Have a serious concomitant systemic disorder (eg, active infection or a gastrointestinal disorder causing clinically significant symptoms such as nausea, vomiting, diarrhea, or profound immune suppression) that, in the opinion of the investigator, would compromise the patient's ability to adhere to the protocol, including but not limited to the following:
  • Have known human immunodeficiency virus (HIV) infection.
  • Active hepatitis B or C virus infection (screening required) or have other known chronic liver disease
  • Severe renal impairment, interstitial lung disease (ILD), severe dyspnea at rest or requiring oxygen therapy, liver disease diagnosed with Child-Pugh A or higher cirrhosis or history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in clinically significant diarrhea.
  • Have clinically significant cardiopulmonary disease such as:
  • ventricular arrhythmia requiring therapy,
  • uncontrolled hypertension (defined as persistent systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 100 mm Hg on antihypertensive medications), or
  • any history of symptomatic CHF
  • severe dyspnea at rest (CTCAE Grade 3 or above) due to complications of advanced malignancy
  • hypoxia requiring supplementary oxygen therapy except when oxygen therapy is needed only for obstructive sleep apnea
  • presence of ≥ Grade 2 QTc prolongation on screening ECG
  • conditions potentially resulting in drug-induced prolongation of the QT interval or torsade de pointes:
  • 1. Congenital or acquired long QT syndrome 2. Family history of sudden death 3. History of previous drug induced QT prolongation 4. Current use of medications with known and accepted associated risk of QT prolongation (see row "Accepted Association" in Appendix 8 15. Have known myocardial infarction or unstable angina within 6 months prior to first dose of study treatment 16. Require therapy with warfarin or other coumarin derivatives (non-coumarin anticoagulants are allowed) 17. Have inability to swallow pills or significant gastrointestinal disease which would preclude the adequate oral absorption of medication 18. Patients with altered mental status or psychiatric disorder that, in the opinion of the investigator, would preclude a valid patient informed consent.
  • 19. Person deprived of liberty or placed under a legal protection regime with representation of the person.
  • 20. Inability to comply with medical monitoring of the trial for geographic, social or psychological reasons.
  • -

Trial locations and contacts

13 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Fouzia Azzouz contact

0147112366

drci.promotion@curie.fr

Sandra Nespoulous contact

0147111654

drci.promotion@curie.fr

13 sites in 1 country

France13 sites, 10 recruiting

  • CHU Amiens Picardie-Site Sud

    Amiens, 80054

    MOREIRA Aurélie, MD

    Aurélie MOREIRA, MD

    Recruiting

  • Institut Sainte Catherine

    Avignon, 84000

    Julien GRENIER, MD

    Julien GRENIER, MD

    Recruiting

  • Centre François Baclesse

    Caen, 14076

    George EMILE, MD

    George EMILE, MD

    Recruiting

  • Centre Jean Perrin

    Clermont-Ferrand, Clermont Ferrand, 63011

    Suspended

  • Centre Georges-François Leclerc

    Dijon, 21079

    Isabelle DESMOULIN, MD

    Isabelle DESMOULIN, MD

    Recruiting

  • Centre Oscar Lambret

    Lille, 59020

    Stéphanie BECOURT, MD

    Stéphanie BECOURT, MD

    Recruiting

  • Institut Du Cancer Montpellier

    Montpellier, 34298

    Suspended

  • Hôpital Privé du Confluent

    Nantes, 44277

    Cyriac BLONZ, MD

    Cyriac BLONZ, MD

    Recruiting

  • Institut Curie

    Paris, 75005

    Delphine LOIRAT, MD

    Delphine LOIRAT, MD

    Recruiting

  • Hopital Saint-Louis Ap-Hp Senopole

    Paris, 75010

    Delphine COCHEREAU, MD

    Delphine COCHEREAU, MD

    Not yet recruiting

  • Centre CARIO-Hôpital Privé des Côtes d'Armor (HPCA)

    Plérin, 22190

    Jérôme MARTIN-BABAU, MD

    Jérôme MARTIN-BABAU, MD

    Recruiting

  • Institut Curie

    Saint-Cloud, 92210

    Florence LEREBOURS, MD

    Florence LEREBOURS, MD

    Recruiting

  • Oncopole Claudius Regaud

    Toulouse, 31059

    Suspended

Other trials in France

About this study

Official title: Tucatinib in Combination With Oral Etoposide (VP16) - Trastuzumab in Patients With Metastatic HER2+ Breast Cancer After Progression Under Tucatinib-Capecitabine-Trastuzumab or Toxicity Related to Capecitabine: a Multicenter Phase II

This is an open-label, multicenter, phase II study to evaluate the efficacy, safety, tolerability, pharmacokinetics of the combination of tucatinib-Oral VP16-trastuzumab in patients with HER2-positive metastatic breast cancer (HER2+ MBC) after progression on tucatinib-capecitabine-trastuzumab or capecitabine-related toxicity.

Read the detailed description

This is an open-label, multicenter, phase II study to evaluate the efficacy, safety, tolerability, pharmacokinetics of the combination of tucatinib-Oral VP16-trastuzumab in patients with HER2-positive metastatic breast cancer (HER2+ MBC) after progression on tucatinib-capecitabine-trastuzumab or capecitabine-related toxicity.

The study has two sequential parts:

  • Part 1 is a safety run-in part evaluating the safety of the combination to confirm the recommended dose;
  • Part 2 will evaluate the efficacy of the combination at the recommended dose. Both parts will include patients with HER2 positive metastatic breast cancer.

In part 1, a D-dose is evaluated; only in case of unacceptable toxicity at the D-dose, a D-1 dose will be investigated.

In part 2, patients will be treated with oral VP16 at the dose recommended in part 1.

Dose reductions will be allowed on subsequent cycles in case of toxicity.

All enrolled patients will receive the combination of tucatinib, oral VP16, trastuzumab until disease progression, unacceptable toxicity, and withdrawal of patient consent, investigator decision, and loss to follow-up, death, patient non-compliance, or discontinuation of the study by the sponsor.

Tumor assessments should be performed according to RECIST v1.1 criteria at baseline and every 6 weeks (± 7 days) for the first 24 weeks, then every 9 weeks (± 7 days) until documented disease progression, withdrawal of consent, or death.

Being tested
Tucatinib in Combination of Oral VP16 and trastuzumab

What participants receive

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

  • Tucatinib in Combination of Oral VP16 and trastuzumabDrug

    Combination of tucatinib-Oral VP16-trastuzumab

Study groups in NCT05955170
Study groupRoleWhat they receive
Combination of tucatinib-Oral VP16-trastuzumabExperimentalThe safety run in part will be a safety evaluation including 6 patients at dose D of Oral VP16 per day, trastuzumab 600mg SC flat dose or 6mg/kg IV every 3 weeks and tucatinib 300mg PO BID. The evaluable population for DLT in this Part 1 is defined as patients who have completed the first 2 cycles of treatment (i.e.6 weeks) and received 100% of the planned dose of tucatinib-Oral VP16-trastuzumab.Patients treated at Dose Recommended during the safety run-in part will be considered as evaluable for the part II.
Receives: Drug: Tucatinib in Combination of Oral VP16 and trastuzumab

What is being measured

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

  1. Objective response rate (ORR

    The objective response rate (ORR) is defined as the best response defined as complete or partial response occurring within the first 6 months of treatment, assessed by the investigators (according to RECIST v1.1 criteria)

    Measured: 6 months

Secondary outcomes (8)

  1. Serious adverse events

    Serious adverse events (SAEs)according to NCI CTCAE v5.0, by grade and their relationship to tucatinib-Oral VP16-trastuzumab.

    Measured: From inclusion until 30 days after the last dose of IMP, up to 24 months

  2. Adverse events

    Adverse events (AEs) according to NCI CTCAE v5.0, by grade and their relationship to tucatinib-Oral VP16-trastuzumab.

    Measured: From inclusion until 30 days after the last dose of IMP, up to 24 months

  3. Progression free survival

    Progression free survival (PFS) is defined as the time from the date of inclusion until progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause. The measure of interest is the median PFS

    Measured: From inclusion until Progression or Death, up to 24 months

  4. Overall survival

    Overall survival (OS) is defined as the time from inclusion to the date of death due to any cause. The measure of interest is the median OS (if reached).

    Measured: From inclusion until Progression or Death, up to 24 months

  5. Duration of response

    Duration of response (DoR) as defined as the time from the date of first documented response until date of documented progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause. The measure of interest is the median DoR

    Measured: From inclusion until Progression or Death, up to 24 months

  6. Time to response

    Time to response (TTR) as defined as the time from the start of treatment to the first ORR observed for patients who achieved a CR or PR. The measure of interest is the median TTR.

    Measured: 6 months

  7. Clinical benefit rate

    Clinical benefit rate (CBR) is defined as the percentage of patients with CR, PR, or stable disease (SD) according to RECIST 1.1, as assessed by the investigator at the local site. The measure of interest is CBR at 24 weeks

    Measured: 6 months

  8. EQ-5D-5L scale

    The measure of interest is the mean difference in the change from baseline in EQ-5D-5L scale. Time to deterioration in pain, physical functioning, role functioning and global health status/QoL. The EQ VAS score is rated on a scale of 0-100 points. 0 points correspond to the worst possible health status

    Measured: From inclusion until Progression or Death, up to 24 months

Timeline

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

  1. First posted21 Jul 2023
  2. Study start19 Dec 2023
  3. Primary completion19 Dec 2027 (estimated)
  4. Study completion19 Dec 2028 (estimated)

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Open-label, multicenter, phase II study to evaluate the efficacy, safety, tolerability, pharmacokinetics of the combination of tucatinib-Oral VP16-trastuzumab in patients with HER2-positive metastatic breast cancer (HER2+ MBC) after progression on tucatinib-capecitabine-trastuzumab or capecitabine-related toxicity.
Masking
None (open label)
Enrolment
66 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05955170
Sponsor's protocol ID
IC 2021-06
Acronym
TUC-TOC
Status last verified
Mar 2025
First submitted
4 Jul 2023
Last updated
27 Mar 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tucatinib in Combination of Oral VP16 and trastuzumab in people with HER2-positive Breast Cancer, run by Institut Curie at 13 sites in France.

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 25 inclusion and 32 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: looking for participants now, as of the sponsor's last update on 27 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in France. 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 phase mean?

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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Fouzia Azzouz (0147112366, drci.promotion@curie.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (ORR (time frame: 6 months). 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 NCT05955170.

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 27 Mar 2025.

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