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HER2-positive Breast CancerPhase 1NCT04602117

ISPY-P1.01:Evaluating the Safety of Weekly Paclitaxel With Trastuzumab Duocarmazine (SYD985) in Patients With Metastatic Cancer

A Phase 1 study testing Vic-trastuzumab duocarmazine (SYD985) + paclitaxel in people with HER2-positive Breast Cancer and HER2 Low, run by QuantumLeap Healthcare Collaborative at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is an open-label, single-arm, multi-site phase I/Ib trial with SYD985, an antibody-drug conjugate (ADC) targeting HER2 on the cell membrane, combined with paclitaxel. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
HER2-positive Breast Cancer, HER2 Low, SYD-985
What is being tested?
Vic-trastuzumab duocarmazine (SYD985) + paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
28 Jul 2021to 17 Nov 2021
Phase
Phase 1
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
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Signed informed consent and for collection of archival FFPE blocks (freshly cut 14 unstained tumor slides would be acceptable) obtained prior to any study specific assessments and procedures.
  • Histologic diagnosis: Biopsy-proven solid malignancy diagnosis of one of the below mentioned types, that is advanced.
  • ER, PgR and HER2 measurements should be performed according to institutional guidelines, in a CLIA-approved setting, when indicated. Cut-off values for positive/negative staining should be in accordance with current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines2-4 published in 2017 for Gastroesophageal Adenocarcinoma, and in 2018 for breast cancer. For other histologic types, HER2 assessment will follow local institutional criteria. Patients with breast cancer and equivocal HER2 in situ hybridization results according to current ASCO/CAP guidelines are eligible..
  • Cohort A (de-escalation):
  • HER2 POSITIVE: breast, gastroesophageal adenocarcinoma, colorectal, ovarian, endometrial and urothelial tumors
  • HER2 LOW: breast (irrespective of HR status)
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  • Cohort B (expansion):
  • HER2 POSITIVE: breast
  • HER2 LOW: breast (irrespective of HR status)
  • Prior therapy: disease has progressed after at least one line of standard/approved therapy in the advanced setting:
  • Histology: Breast HER2 pos
  • Prior treatment lines allowed
  • Must have received at least a taxane and trastuzumab for advanced/metastatic disease.
  • Recurrence during or within 6 months of end of adjuvant therapy counts as 1 line.
  • No more than 4 lines of anti-HER2 therapy for advanced/ metastatic disease.
  • Trastuzumab beyond progression: each chemotherapy regimen combined with trastuzumab counts as a separate line also when that regimen is interrupted for any time and any other reason than recovery from drug-related toxicity or when chemotherapy is recycled.
  • Breast HER2low
  • HR neg
  • (TN)
  • No more than 2 lines of systemic cytotoxic therapy for advanced/metastatic disease; antibody drug conjugate counts as cytotoxic therapy.
  • No limit number of lines for prior immunotherapy, PI3Kinase/AKT pathway inhibitors or PARP inhibitors. However, no more than one PARP inhibitor is allowed.
  • Breast HER2low
  • HR pos
  • (ER/PR pos)
  • No more than 2 lines of systemic cytotoxic therapy for advanced/metastatic disease; antibody drug conjugate counts as cytotoxic therapy.
  • No limit number of lines for endocrine therapy, CDK4/6 inhibitors, PI3Kinase/AKT pathway inhibitors, PARP inhibitors or immunotherapy.
  • Gastroesophageal adenocarcinoma
  • Must have received at least one prior HER2 targeted therapy for advanced/metastatic disease.
  • No more than 2 lines of systemic cytotoxic therapy.
  • Other histology: colorectal, ovarian, endometrial and urothelial
  • No more than 2 lines of systemic cytotoxic therapy for advanced/metastatic disease.
  • ECOG performance status 0-2 (Appendix E: ECOG PS scale).
  • Estimated life expectancy > 12 weeks at the start of investigational medicinal product (IMP) treatment.
  • Measurable disease: for Cohort B (expansion) only, at least one measurable cancer lesion as defined by the Response Evaluation Criteria for Solid Tumors (RECIST version 1.1);
  • Adequate organ function, evidenced by the following laboratory results:
  • Absolute neutrophil count ≥ 1,500/mm3
  • Platelet count ≥ 100,000/mm3
  • Hemoglobin ≥ 9.0 g/dL with no blood transfusion in the past 28 days
  • Total bilirubin ≤ 1.5 x the upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN (or ≤ 5.0 x ULN in the presence of liver metastases)
  • Serum creatinine within normal institutional limits or creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with serum creatinine levels above institutional ULN.
  • Non-Pregnant: Serum or urine pregnancy test must be negative within 14 days of treatment start in women of childbearing potential. Pregnancy testing does not need to be pursued in patients who are judged as postmenopausal before enrollment, or who have undergone bilateral oophorectomy, total hysterectomy, or bilateral tubal ligation.
  • Contraception: Willingness to undergo adequate contraception if childbearing potential. Women of childbearing potential and men must use adequate contraception for the duration of protocol treatment and for 6 months after the last treatment with SYD985/paclitaxel. Adequate contraception is defined as one highly effective form (i.e. abstinence, (fe)male sterilization) OR two effective forms (e.g. non-hormonal IUD and condom / occlusive cap with spermicidal foam / gel / film / cream / suppository).
  • Prior therapy effects: Resolution of all acute toxic effects of prior therapy, including radiotherapy to grade ≤1 and neuropathy to grade ≤2 (except toxicities not considered a safety risk for the patient) and recovery from surgical procedures.
  • Patient compliance: patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Who cannot join

  • Anthracycline treatment within 3 months prior to start IMP treatment.
  • Wash out periods: Other anticancer therapy as below within the following period.
  • chemotherapy or investigational agents, 3 weeks
  • mitomycin C and nitrosoureas, 6 weeks
  • radiotherapy, 4 weeks
  • targeted therapy and endocrine therapy, 2 weeks
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  • MAbs and immunotherapy, 4 weeks
  • Concurrent therapy with other Investigational Products.
  • Trastuzumab hypersensitivity: History of infusion-related reactions and/or hypersensitivity to trastuzumab (as antibody or as part of antibody-drug conjugate), trastuzumab emtansine or excipients of the study drug which led to permanent discontinuation of the treatment.
  • Uncontrolled intercurrent illness including (active infection, diabetes, pulmonary embolism in the past 6 months, or psychiatric illness/social situations that would limit compliance with study requirements).
  • Cardiovascular disease: History (within 6 months prior to start IMP) of clinically significant cardiovascular disease such as unstable angina, congestive heart failure (CHF), myocardial infarction, uncontrolled hypertension, cardiac arrhythmia requiring medication, or baseline corrected QT by Fridericia's formula (QTcF) length ≥ 450 ms for men and ≥ 470 ms for women.History (within 6 months prior to start IMP) of clinically significant cardiovascular disease such as unstable angina, congestive heart failure (CHF), myocardial infarction, uncontrolled hypertension, or cardiac arrhythmia requiring medication.
  • Left ventricular ejection fraction (LVEF) < 50% as assessed by either echocardiography or multiple-gated acquisition (MUGA) scan at study screening; or a history of absolute decrease in LVEF of ≥ 10% points to < 50% during previous treatment with trastuzumab or trastuzumab emtansine, or a history of decrease in LVEF to < 40% during previous treatment with trastuzumab or trastuzumab emtansine.
  • Interstitial Lung Disease (ILD): History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. If lung infiltrates are visible other tests such as a breast MRI, additional testing will be required to establish possible cause for findings.
  • Eye disease: Keratitis, or other clinically significant corneal disease, diagnosed by an ophthalmologist. Exam includes a slit lamp exam and fluorescence tear film break-up time. Pachymetry is optionalExam includes a slit lamp exam, corneal sensitivity testing, fluorescence tear film break-up time, and pachymetry.
  • CNS tumoral spread: Active uncontrolled/symptomatic central nervous system cancer/spinal cord compression. Previously treated and clinically stable lesions, as per Investigator's judgment, are permitted.
  • Liver disease: Patients with clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis.
  • Recent major surgery within 4 weeks prior to start IMP treatment
  • Pregnancy or lactation
  • Other condition, which in the opinion of the investigator, would compromise the safety of the patient or the patient's ability to complete the study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Colorado Cancer Center

    Aurora, Colorado, 80045

Other trials in United States

About this study

Official title: ISPY-P1.01: Evaluating the Safety of Weekly Paclitaxel With Trastuzumab Duocarmazine (SYD985) in Patients With Metastatic Cancer: A Phase I/Ib Trial

This is an open-label, single-arm, multi-site phase I/Ib trial with SYD985, an antibody-drug conjugate (ADC) targeting HER2 on the cell membrane, combined with paclitaxel.

Read the detailed description

The study contains 2 cohorts. Cohort A is a 3+3 de-escalation cohort. Participants with certain HER-positive advanced solid tumors or HER2-low breast cancer will be enrolled in this cohort. Eligible participants will receive infusions of SYD985 every three weeks and of paclitaxel weekly. Participants will be monitored for safety and for the occurance of DLTs. Cohort B dose expansion will proceed at the identified dose from Cohort A (RP2D). Cohort B will only enroll patients with HER2-positive or HER2-low breast cancer.

Being tested
Vic-trastuzumab duocarmazine (SYD985) + paclitaxel
Keywords
I-SPY Trials, De-escalation, Quantum Leap Healthcare Collaborative, QLHC, ADC, SYD985
Medical subject headings
Neoplasm Metastasis, Breast Neoplasms, Endometrial Neoplasms, Ovarian Neoplasms, Triple Negative Breast Neoplasms, Urinary Bladder Neoplasms

What participants receive

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

  • Vic-trastuzumab duocarmazine (SYD985) + paclitaxelDrug

    Also called SYD985, paclitaxel, SYD-985, Taxol

    SYD985 ([vic-]trastuzumab duocarmazine) an antibody-drug conjugate or ADC being developed by Byondis B.V. (Nijmegen, The Netherlands), consists of the recombinant humanized anti-epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab linked, via a cleavable linker, to the duocarmycin prodrug, seco-duocarmycin-hydroxybenzamide-azaindole or seco-DUBA, which has potent antineoplastic activity.

    Eligible patients will receive infusions of SYD985 every three weeks and of paclitaxel weekly.

Study groups in NCT04602117
Study groupRoleWhat they receive
Vic-trastuzumab duocarmazine (SYD985) + paclitaxelExperimentalSingle-arm, phase I trial with SYD985, an antibody-drug conjugate (ADC) targeting HER2 on the cell membrane, combined with paclitaxel. The study contains 2 cohorts. Cohort A is the de-escalation cohort. Patients with certain HER-positive advanced solid tumors or HER2-low breast cancer will be enrolled in this cohort. Cohort B is the expansion cohort, in which only patients with HER2-positive or HER2-low breast cancer can be enrolled. Treatment will be administered on an outpatient basis.
Receives: Drug: Vic-trastuzumab duocarmazine (SYD985) + paclitaxel

What is being measured

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

  1. Common Toxicity Criteria for Adverse Events (CTCAE 5.0)

    To determine safety and tolerability of the weekly paclitaxel with tri-weekly trastuzumab duocarmazine (SYD985) combination in patients with certain advanced solid tumors

    Toxicity, incidence and grade, Dose Limiting Toxicity (DLT), Maximum Tolerated Dose (MTD), Recommended Phase 2 Dose (RP2D)

    Measured: up to 12 months

  2. Clinical Benefit Rate (CBR) at 6 months

    To obtain Preliminary efficacy data of the weekly paclitaxel with tri-weekly trastuzumab duocarmazine (SYD985) combination in patients with certain advanced solid tumors

    Outcome measure: RECIST 1.1

    Measured: up to 6 months

  3. Overall response rate (ORR)

    To obtain Preliminary efficacy data of the weekly paclitaxel with tri-weekly trastuzumab duocarmazine (SYD985) combination in patients with certain advanced solid tumors

    Outcome measure: RECIST 1.1

    Measured: up to 6 months

Secondary outcomes (2)

  1. Progression Free Survival (PFS) of patients treated with the weekly paclitaxel with tri-weekly trastuzumab duocarmazine (SYD985) combination

    Endpoint: PFS

    RECIST 1.1

    Measured: up to 12 months

  2. Duration of response (DOR) of patients treated with the weekly paclitaxel with tri-weekly trastuzumab duocarmazine (SYD985) combination

    Endpoints: Duration of response

    Outcome measures:

    Measured: up to 12 months

Timeline

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

  1. First posted26 Oct 2020
  2. Study start28 Jul 2021
  3. Primary completion17 Nov 2021
  4. Study completion17 Nov 2021

Why it stopped: Study withdrawn as scientific interest in pursuing the SYD985+Paclitaxel combination has diminished.

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This is an open-label, 3+3 design, single-arm, phase I trial with SYD985, an antibody-drug conjugate (ADC) targeting HER2 on the cell membrane, combined with paclitaxel.
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04602117
Sponsor's protocol ID
ISPY-P1.01
Status last verified
Nov 2023
First submitted
12 Oct 2020
Last updated
18 Nov 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vic-trastuzumab duocarmazine (SYD985) + paclitaxel in people with HER2-positive Breast Cancer and HER2 Low, run by QuantumLeap Healthcare Collaborative at 1 site 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 45 inclusion and 19 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 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 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.

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?

Common Toxicity Criteria for Adverse Events (CTCAE 5.0) (time frame: up to 12 months). The study lists 3 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 NCT04602117.

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 18 Nov 2023.

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