Trial Title:
Tucatinib in Combination With Oral Etoposide andTrastuzumab in Patients With Metastatic HER2+ Breast Cancer
NCT ID:
NCT05955170
Condition:
HER2-positive Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Trastuzumab
Tucatinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention 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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Tucatinib in Combination of Oral VP16 and trastuzumab
Description:
Combination of tucatinib-Oral VP16-trastuzumab
Arm group label:
Combination of tucatinib-Oral VP16-trastuzumab
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.
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. 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).
2. Age > 18 years,
3. Histologically confirmed HER2+ breast carcinoma (ASCO/CAP guidelines) with archived
tumor tissue available,
4. Have a life expectancy of at least 3 months,
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1,
6. Participants must be able to swallow capsules,
7. Participants must be able and willing to be available for the duration of the study
and are willing to follow study procedures,
8. Measurable disease, assessed by RECIST version 1,
9. 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
10. Relevant records of any CNS treatment must be available to allow for classification
of target and non-target lesions
11. Left ventricular ejection fraction (LVEF) ≥ 50% (within 4 weeks before inclusion)
12. 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).
13. 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.
Exclusion Criteria:
1. 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).
2. 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.
3. 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)
4. Patients unable for any reason to undergo MRI of the brain.
5. Leptomeningeal metastases or brain metastases requiring immediate symptomatic
treatment or a high dose of corticosteroid therapy (≥2mg/day dexamethasone or
equivalent).
6. Have poorly controlled (> 1/week) generalized or complex partial seizures, or
manifest neurologic progression due to brain metastases notwithstanding CNS-directed
therapy
7. Any toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1 at
time of treatment start, with the following exceptions:
1. Alopecia and neuropathy (must have resolved to ≤ Grade 2)
2. Congestive Heart Failure (must have been ≤ Grade 1 in severity at the time of
occurrence and must have resolved completely)
3. Anemia (must have resolved to ≤ Grade 2)
8. 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.
9. Patients who have had any major surgery within 28 days prior to inclusion.
10. 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.
11. Concomitant use of other agents for the treatment of cancer or any investigational
agent(s).
12. Women who are either pregnant, lactating, planning to get pregnant
13. 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:
1. Have known human immunodeficiency virus (HIV) infection.
2. Active hepatitis B or C virus infection (screening required) or have other
known chronic liver disease
3. 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.
14. 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.
-
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Centre Jean Perrin
Address:
City:
Clermont-Ferrand
Zip:
63011
Country:
France
Status:
Suspended
Facility:
Name:
CHU Amiens Picardie-Site Sud
Address:
City:
Amiens
Zip:
80054
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
MOREIRA Aurélie, MD
Investigator:
Last name:
Aurélie MOREIRA, MD
Email:
Principal Investigator
Facility:
Name:
Institut Sainte Catherine
Address:
City:
Avignon
Zip:
84000
Country:
France
Status:
Recruiting
Contact:
Last name:
Julien GRENIER, MD
Investigator:
Last name:
Julien GRENIER, MD
Email:
Principal Investigator
Facility:
Name:
Centre François Baclesse
Address:
City:
Caen
Zip:
14076
Country:
France
Status:
Recruiting
Contact:
Last name:
George EMILE, MD
Investigator:
Last name:
George EMILE, MD
Email:
Principal Investigator
Facility:
Name:
Centre Georges-François Leclerc
Address:
City:
Dijon
Zip:
21079
Country:
France
Status:
Recruiting
Contact:
Last name:
Isabelle DESMOULIN, MD
Investigator:
Last name:
Isabelle DESMOULIN, MD
Email:
Principal Investigator
Facility:
Name:
Centre Oscar Lambret
Address:
City:
Lille
Zip:
59020
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Stéphanie BECOURT, MD
Investigator:
Last name:
Stéphanie BECOURT, MD
Email:
Principal Investigator
Facility:
Name:
Institut Du Cancer Montpellier
Address:
City:
Montpellier
Zip:
34298
Country:
France
Status:
Suspended
Facility:
Name:
Hôpital Privé du Confluent
Address:
City:
Nantes
Zip:
44277
Country:
France
Status:
Recruiting
Contact:
Last name:
Cyriac BLONZ, MD
Investigator:
Last name:
Cyriac BLONZ, MD
Email:
Principal Investigator
Facility:
Name:
Institut Curie
Address:
City:
Paris
Zip:
75005
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Delphine LOIRAT, MD
Investigator:
Last name:
Delphine LOIRAT, MD
Email:
Principal Investigator
Facility:
Name:
Hopital Saint-Louis Ap-Hp Senopole
Address:
City:
Paris
Zip:
75010
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Emilie MOATI, MD
Investigator:
Last name:
Emilie MOATI, MD
Email:
Principal Investigator
Facility:
Name:
Centre CARIO-Hôpital Privé des Côtes d'Armor (HPCA)
Address:
City:
Plerin
Zip:
22190
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Jérôme MARTIN-BABAU, MD
Investigator:
Last name:
Jérôme MARTIN-BABAU, MD
Email:
Principal Investigator
Facility:
Name:
Institut Curie
Address:
City:
Saint Cloud
Zip:
92210
Country:
France
Status:
Recruiting
Contact:
Last name:
Florence LEREBOURS, MD
Investigator:
Last name:
Florence LEREBOURS, MD
Email:
Principal Investigator
Facility:
Name:
Oncopole Claudius Regaud
Address:
City:
Toulouse
Zip:
31059
Country:
France
Status:
Suspended
Start date:
December 19, 2023
Completion date:
December 19, 2027
Lead sponsor:
Agency:
Institut Curie
Agency class:
Other
Collaborator:
Agency:
Seagen Inc.
Agency class:
Industry
Source:
Institut Curie
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05955170
