NCT05955170

Brief 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 toxicity.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
66

participants targeted

Target at P50-P75 for phase_2

Timeline
31mo left

Started Dec 2023

Longer than P75 for phase_2

Geographic Reach
1 country

13 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress49%
Dec 2023Dec 2028

First Submitted

Initial submission to the registry

July 4, 2023

Completed
17 days until next milestone

First Posted

Study publicly available on registry

July 21, 2023

Completed
5 months until next milestone

Study Start

First participant enrolled

December 19, 2023

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 19, 2027

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 19, 2028

Last Updated

March 27, 2025

Status Verified

March 1, 2025

Enrollment Period

4 years

First QC Date

July 4, 2023

Last Update Submit

March 26, 2025

Conditions

HER2-positive Breast Cancer

Outcome Measures

Primary Outcomes (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)

    6 months

Secondary Outcomes (8)

  • Serious adverse events

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

  • Adverse events

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

  • Progression free survival

    From inclusion until Progression or Death, up to 24 months

  • Overall survival

    From inclusion until Progression or Death, up to 24 months

  • Duration of response

    From inclusion until Progression or Death, up to 24 months

  • +3 more secondary outcomes

Study Arms (1)

Combination of tucatinib-Oral VP16-trastuzumab

EXPERIMENTAL

The 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.

Drug: Tucatinib in Combination of Oral VP16 and trastuzumab

Interventions

Tucatinib in Combination of Oral VP16 and trastuzumabDRUG

Combination of tucatinib-Oral VP16-trastuzumab

Combination of tucatinib-Oral VP16-trastuzumab

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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,
  • 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
  • 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
  • +9 more criteria

You may not qualify if:

  • 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/ 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).
  • 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.
  • 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
  • +15 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (13)

Centre Jean Perrin

Clermont-Ferrand, Clermont Ferrand, 63011, France

SUSPENDED

CHU Amiens Picardie-Site Sud

Amiens, 80054, France

RECRUITING

Institut Sainte Catherine

Avignon, 84000, France

RECRUITING

Centre François Baclesse

Caen, 14076, France

RECRUITING

Centre Georges-François Leclerc

Dijon, 21079, France

RECRUITING

Centre Oscar Lambret

Lille, 59020, France

RECRUITING

Institut Du Cancer Montpellier

Montpellier, 34298, France

SUSPENDED

Hôpital Privé du Confluent

Nantes, 44277, France

RECRUITING

Institut Curie

Paris, 75005, France

RECRUITING

Hopital Saint-Louis Ap-Hp Senopole

Paris, 75010, France

NOT YET RECRUITING

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

Plérin, 22190, France

RECRUITING

Institut Curie

Saint-Cloud, 92210, France

RECRUITING

Oncopole Claudius Regaud

Toulouse, 31059, France

SUSPENDED

MeSH Terms

Interventions

tucatinibTrastuzumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • François-Clément Bidard

    Institut Curie

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Fouzia Azzouz

CONTACT

0147112366drci.promotion@curie.fr

Sandra Nespoulous

CONTACT

0147111654drci.promotion@curie.fr

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 4, 2023

First Posted

July 21, 2023

Study Start

December 19, 2023

Primary Completion (Estimated)

December 19, 2027

Study Completion (Estimated)

December 19, 2028

Last Updated

March 27, 2025

Record last verified: 2025-03

Data Sharing

IPD Sharing
Will share

Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.
Access Criteria
Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific reserach, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).

Locations

FR(13)