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Breast CancerPhase 1/2NCT04298918

A Study Evaluating the Safety and Efficacy of Venetoclax in Combination With Trastuzumab Emtansine in Patients With Previously Treated HER2-Positive Locally Advanced or Metastatic Breast Cancer

A Phase 1/2 study testing Venetoclax and Trastuzumab emtansine in people with Breast Cancer, run by Hoffmann-La Roche at 3 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This two-part study is composed of two stages: a Phase Ib stage consisting of a dose-escalation phase and an expansion phase; and a Phase II, randomized, placebo-controlled, double-blind, multicenter stage. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Venetoclax and Trastuzumab emtansine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1 participants
Where
3 sitesin 2 countries
Study dates
23 Sep 2020to 4 Feb 2021
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Histologically or cytologically confirmed invasive metastatic breast cancer (MBC) or locally advanced breast cancer (LABC) that is incurable, unresectable, and previously treated with multimodality therapy
  • Measurable disease that is evaluable per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Willing to provide tumor biopsy sample at the time of screening
  • Local histological or cytological confirmation of estrogen receptor (ER) and/or progesterone receptor status as defined by using immunohistochemistry (IHC) per American Society of Clinical Oncology/College of American Pathologists criteria
  • Percentage of ER and/or progesterone receptor positivity, if available
Show all 17Show fewer
  • Willing to provide blood samples at the time of screening, on-study, and at progression for exploratory research on biomarkers
  • HER2-positive BC as defined by an IHC score of 3+ or gene amplified by in situ hybridization (ISH) as defined by a ratio of >/= 2.0 for the number of HER2 gene copies to the number of chromosome 17 copies
  • Adequate hematologic and end-organ function
  • Screening left ventricular ejection fraction (LVEF) >/= 50% on echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan
  • Negative HIV test, hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
  • Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 30 days after the last dose of venetoclax or 7 months after the last dose of trastuzumab emtansine
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm during the treatment period and for at least 30 days after the last dose of venetoclax or 7 months after the last dose of trastuzumab emtansine
  • In addition to the general inclusion criteria, participants in the expansion phase must also meet the following criteria for study entry:
  • Trastuzumab emtansine experienced cohort: Disease progression during or after trastuzumab emtasine in the advanced/metastatic setting or disease recurrence in the neoadjuvant/adjuvant setting; At least 50% of participants in the expansion cohort must have a tumor that is Bcl-2 high (defined as >50% of tumor cells stained with an intensity of immunohistochemistry (IHC) 2+ or 3+)
  • Trastuzumab deruxtacan (DS-8201a) experienced cohort: Disease progression during or after trastuzumab deruxtecan in the advanced/metastatic setting; Prior trastuzumab emtansine in any setting is allowed; At least 50% of participants in the expansion cohort must have a tumor that is Bcl-2 high

Who cannot join

  • Receipt of any anticancer drug/biologic or investigational treatment 21 days prior to Cycle 1, Day 1 except hormone therapy, which can be given up to 7 days prior to Cycle 1, Day 1
  • Radiation therapy within 2 weeks prior to Cycle 1, Day 1
  • History of exposure to the following cumulative doses of anthracyclines as specified: Doxorubicin >500 mg/m2; Liposomal doxorubicin >500 mg/m2; Epirubucin >720 mg/m2; Mitoxantrone >120 mg/m2; Idarubicin >90 mg/m2. If another anthracycline or more than one anthracycline has been used, then the cumulative dose must not exceed the equivalent of 500 mg/m2 doxorubicin.
  • History of other malignancy within the previous 5 years
  • Cardiopulmonary dysfunction
  • Current severe, uncontrolled systemic disease
Show all 34Show fewer
  • Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
  • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1, Day 1
  • Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, autoimmune hepatic disorders, sclerosis cholangitis, or active infection with HBV or HCV)
  • Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
  • Known HIV infection or human T-cell leukemia virus 1 infection
  • Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to randomization
  • Known central nervous system (CNS) disease
  • Leptomeningeal disease
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
  • Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
  • Current Grade >/= 3 peripheral neuropathy
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies, excipients of any drugs formulated in polysorbate 80 or 20 or fusion proteins
  • Prior allogeneic stem cell or solid organ transplantation
  • Pregnant or breastfeeding, or intending to become pregnant during the study or within 30 days after the last dose of venetoclax or 7 months after the last dose of trastuzumab emtansine after the final dose of study treatment, whichever is later
  • Consumption of grapefruit, grapefruit products, Seville oranges, or starfruit within 3 days before anticipated first dose of study drug until the last dose of study drug
  • Administration of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during the study
  • Illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment
  • Malabsorption syndrome or other condition that would interfere with enteral absorption
  • History of active inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) requiring specific medication in the 12 months prior to randomization, or active and uncontrolled bowel inflammation (e.g., diverticulitis) at time of randomization
  • Inability or unwillingness to swallow a large number of tablets
  • Known hypersensitivity to venetoclax or trastuzumab emtansine or to any of their excipients
  • Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
  • Other medical or psychiatric conditions that, in the opinion of the investigator, may interfere with the patient's participation in the study
  • Blood transfusions if performed within 2 weeks prior to screening
  • In addition to the general exclusion criteria, participants in the randomized Phase II stage who meet the following criteria will be excluded:
  • Prior treatment with trastuzumab emtansine in any setting (neoadjuvant/adjuvant or advanced/metastatic setting)
  • Prior treatment with venetoclax in any setting
  • Prior treatment with anti-HER2 antibody drug conjugates (e.g. trastuzumab deruxtecan [DS-8201a]), margetuximab, pyrotinib, or tucatinib)

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

South Korea2 sites

  • Asan Medical Center

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

Other trials in South Korea

Australia1 site

  • Peter MacCallum Cancer Center

    East Melbourne, Victoria, 3002

Other trials in Australia

About this study

Official title: A Phase lb/ll, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Venetoclax in Combination With Trastuzumab Emtansine in Patients With Previously Treated HER2-Positive Locally Advanced or Metastatic Breast Cancer

This two-part study is composed of two stages: a Phase Ib stage consisting of a dose-escalation phase and an expansion phase; and a Phase II, randomized, placebo-controlled, double-blind, multicenter stage. The Phase Ib stage will assess the safety and tolerability, determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D), and evaluate the preliminary efficacy of trastuzumab emtansine in combination with venetoclax in participants with previously treated human epidermal growth factor receptor 2 (HER2) positive unresectable locally advanced breast cancer (LABC) or metastatic breast cancer (MBC). Additional patients may be enrolled in an expansion phase to evaluate the safety, tolerability, and efficacy of trastuzumab emtansine in combination with venetoclax at RP2D in patients with previously treated HER2-positive LABC or MBC who have previously received either trastuzumab emtansine or trastuzumab deruxtecan (DS-8201a). The Phase II randomized stage will evaluate the safety, efficacy, tolerability, and pharmacokinetics of trastuzumab emtansine in combination with venetoclax at RP2D compared with trastuzumab emtansine plus placebo in participants with previously treated HER2-positive LABC or MBC who have not received prior trastuzumab emtansine therapy, either alone or in combination with other anti-cancer therapies.

Conditions
Breast Cancer
Being tested
Placebo, Venetoclax, Trastuzumab emtansine
Medical subject headings
Breast Neoplasms

What participants receive

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

  • PlaceboDrug

    Participants will receive oral placebo in combination with trastuzumab emtansine.

  • VenetoclaxDrug

    Also called Venclexta

    Participants will receive oral venetoclax.

  • Trastuzumab emtansineDrug

    Also called Kadcyla

    Participants will receive intravenous (IV) trastuzumab emtansine.

Study groups in NCT04298918
Study groupRoleWhat they receive
Dose Escalation PhaseExperimentalParticipants received venetoclax in combination with a fixed dose of trastuzumab emtansine.
Receives: Drug: Venetoclax; Drug: Trastuzumab emtansine
Dose Expansion PhaseExperimentalParticipants were to receive venetoclax at the Phase II Recommended Dose (RP2D) in combination with trastuzumab emtansine.
Receives: Drug: Venetoclax; Drug: Trastuzumab emtansine
Randomized Phase II Arm 1ExperimentalParticipants were to receive trastuzumab emtansine + placebo.
Receives: Drug: Placebo; Drug: Trastuzumab emtansine
Randomized Phase II Arm 2ExperimentalParticipants were to receive trastuzumab emtansine + venetoclax.
Receives: Drug: Venetoclax; Drug: Trastuzumab emtansine

What is being measured

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

  1. Dose Escalation: Number of Participants With Adverse Events

    The study was terminated by the Sponsor. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.

    Measured: Baseline up until 28 days after the last dose of study drug or until initiation of new systemic anti-cancer therapy, whichever occurs first (up to a maximum of 20 weeks).

  2. Expansion Phase: Objective Response Rate (ORR)

    The study was terminated by the Sponsor. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.

    Measured: Up to 30 months

  3. Phase II: ORR

    The study was terminated by the Sponsor. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.

    Measured: Up to 30 months

  4. Phase II: Progression-Free Survival (PFS)

    The study was terminated by the Sponsor. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.

    Measured: Up to 30 months

Secondary outcomes (6)

  1. All Phases: Plasma Concentration of Venetoclax

    The study was terminated by the Sponsor. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.

    Measured: At pre-defined time points from Cycle 1 Day 8 and/or Cycle 2 Day 1 through Cycle 4 Day 1 (cycle = 21 days)

  2. Phase II: Serum Concentration of Trastuzumab Emtansine

    The study was terminated by the Sponsor. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.

    Measured: At pre-defined time points from Cycle 1 Day 1 through Cycle 4 Day 1 (cycle = 21 days)

  3. Expansion Phase and Phase II: Number of Participants With Adverse Events

    The study was terminated by the Sponsor. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.

    Measured: Baseline up until 28 days after the last dose of study drug or until initiation of new systemic anti-cancer therapy, whichever occurs first (up to a maximum of 20 weeks).

  4. Expansion Phase and Phase II: Duration of Response (DOR)

    The study was terminated by the Sponsor. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.

    Measured: Up to 30 months

  5. Phase II: Overall Survival (OS)

    The study was terminated by the Sponsor. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.

    Measured: Randomization to death from any cause (up to 30 months)

  6. Phase II: Number of Participants With Anti-Drug Antibodies (ADAs) to Trastuzumab Emtansine

    The study was terminated by the Sponsor. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.

    Measured: Up to 30 months

Timeline

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

  1. First posted6 Mar 2020
  2. Study start23 Sep 2020
  3. Primary completion4 Feb 2021
  4. Study completion4 Feb 2021

Why it stopped: Decision to discontinue the study based on broader development and strategic prioritisation. The Sponsor concludes there is no benefit-risk impact on the CO41863 study.

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
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04298918
Sponsor's protocol ID
CO41863
Other IDs
2019-004200-35, 2019
Status last verified
Oct 2021
First submitted
5 Mar 2020
Last updated
8 Nov 2021
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Venetoclax and Trastuzumab emtansine in people with Breast Cancer, run by Hoffmann-La Roche at 3 sites in 2 countries.

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 17 inclusion and 34 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: stopped early, as of the sponsor's last update on 8 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in South Korea, Australia. 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?

Yes. Results are posted in the registry (first posted 8 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Dose Escalation: Number of Participants With Adverse Events (time frame: Baseline up until 28 days after the last dose of study drug or until initiation of new systemic anti-cancer therapy, whichever occurs first (up to a maximum of 20 weeks).). The study lists 4 primary outcomes in all. 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 NCT04298918.

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 8 Nov 2021.

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