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HER2-positive Breast CancerPhase 2NCT03698383

Phase II Study of Herzuma® Plus Gedatolisib in Patients With HER-2 Positive Metastatic Breast Cancer

A Phase 2 study testing Trastuzumab biosimilars(Herzuma), Gedatolisib in people with HER2-positive Breast Cancer and Metastatic Breast Cancer, run by Korean Cancer Study Group at 1 site in South Korea.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Phase II Pilot Study of Trastuzumab Biosimilar (Herzuma®) plus Gedatolisib in Patients with HER-2 Positive Metastatic Breast Cancer Who Progressed after 2 or more HER-2 directed Chemotherapy Read more about this study

Who is it for?
Ages 19 years and older
What is being tested?
Trastuzumab biosimilars(Herzuma), Gedatolisib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteSouth Korea
Study dates
3 Dec 2019to Dec 2021
Phase
Phase 2
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 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Breast tumor with suspected PI3K-pathway dependence (either by mutation or by known biologic rationale. PI3K dependence includes the presence of a PIK3CA-mutant hotspot mutation, PIK3CA copy number gain, mTOR hotspot mutation, or PTEN loss in the archival or fresh tumor tissue specimen identified in K-MASTER panel. All genetic findings must be reviewed by the study PI, prior to study entry.).
  • Patient is an adult, female ≥ 19 years old at the time of informed consent.
  • Patient has histologically and/or cytologically confirmed diagnosis of HER2-positive breast cancer. HER2-positive breast cancer as defined by an immunohistochemistry (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.Metastatic or unresectable disease documented on diagnostic imaging studies.
  • Metastatic or unresectable disease documented on diagnostic imaging studies.
  • Prior 2 or more HER-2 directed therapy including trastuzumab for metastatic disease is mandatory.
  • Patient must have at least one measurable lesion according to Response valuation Criteria in Solid Tumors version 1.1 (RECIST v.1.1).
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  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
  • Adequate bone marrow and organ function including: WBC ≥ 3500/mL; Platelets ≥ 100,000/uL; Hemoglobin >9.0 g/dL; Total bilirubin ≤ 1.5x ULN; AST and ALT < 2.5 x ULN; Alkaline phosphatase <2.5x ULN; Creatinine ≤ 1.5x ULN or CCr >60 ml/min for patients with abnormal serum Cr level function.
  • Adequate glucose control, as defined by HbA1c < 7% and fasting blood glucose ≤ 126 mg/dL (7.0 mmoL/L).
  • Adequate glucose control, as defined by HbA1c < 7% and fasting blood glucose ≤ 126 mg/dL (7.0 mmoL/L).
  • Life expectancy higher than 3 months
  • Patient has an adequate left ventricular ejection function of at least 50 % at baseline, as measured by echocardiography.
  • Written informed consent

Who cannot join

  • Patient is pregnant or lactating, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
  • Patient has received previous treatment with a mechanistic target of rapamycin (mTOR) inhibitor or phosphoinositide 3-kinase (PI3K) inhibitor.
  • Patient has symptomatic and unstable CNS metastases, except for treated brain metastases. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed.
  • Active and clinically significant bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus syndrome (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness. Baseline viral assessment is not required in patients with no known infection.
  • Current use or anticipated need for food or medications that are known moderate or greater CYP3A4 inhibitors, including their administration within 7-days prior to the first gedatolisib dose and while receiving investigational product (ie, strong CYP3A4 inhibitors: grapefruit juice or grapefruit/grapefruit related citrus fruits [e.g., Seville oranges, pomelos], ketoconazole, miconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, amprenavir, fosamprenavir nefazodone, lopinavir, troleandomycin, mibefradil, conivaptan; moderate CYP3A4 inhibitors: erythromycin, verapamil, atazanavir, delavirdine, fluconazole, darunavir, diltiazem, aprepitant, imatinib, tofisopam, ciprofloxacin, and cimetidine).
  • Concurrent use or anticipated need for medications that are mainly metabolized by UGT1A9 including their administration within 7-days prior to the first dose of investigational product (e.g., propofol, propranolol, dapagliflozin, darexaban, mycophenolic acid, and tapentadol).
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  • Acetaminophen use within 24 hours before or after the first dose of gedatolisib.
  • Current use or anticipated need for food or medications that are metabolized by CYP2D6, and of narrow therapeutic index including their administration within 10-days prior to the first gedatolisib dose and while receiving investigational product.
  • Concurrent use of herbal preparations.
  • Major surgery within 4 weeks of first dose of investigational product or not fully recovered from any side effects of previous procedures.
  • Any other malignancy within 3 years prior to first dose of investigational product except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
  • QTc interval >480 msec (based on the mean value of the triplicate ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes.
  • Any of the following within 6 months of first dose of investigational product myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE v. 5.0 Grade ≤2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.
  • History of interstitial pneumonitis.
  • Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Trial locations and contacts

1 site in 1 country.

Kyong Hwa Park, MD, PhD contact

+821047617651

khpark@korea.ac.kr

Jung Yoon Choi, MD contact

+821072288510

choijy1905@gmail.com

South Korea1 site, 1 recruiting

  • Samsung Medical Center

    Seoul

    Yeon Hee Park, MD, PhD

    Recruiting

Other trials in South Korea

About this study

Official title: Phase II Study of Trastuzumab Biosimilar (Herzuma®) Plus Gedatolisib in Patients With HER-2 Positive Metastatic Breast Cancer Who Progressed After 2 or More HER-2 Directed Chemotherapy

Phase II Pilot Study of Trastuzumab Biosimilar (Herzuma®) plus Gedatolisib in Patients with HER-2 Positive Metastatic Breast Cancer Who Progressed after 2 or more HER-2 directed Chemotherapy

Read the detailed description

All the patients will be included in the final analysis, with a total of 15 patients to be enrolled.

Treatment will occur until disease progression, unacceptable toxicity or patient withdrawal.

Tumor measurement and evaluation are going to be performed at every 6 weeks for the first 3 months, then at every 9 weeks till progression, and then follow-up evaluation at every 12 weeks thereafter end of study.

Being tested
Trastuzumab biosimilars(Herzuma), Gedatolisib
Keywords
Herzuma, Gedatolisib
Medical subject headings
Breast Neoplasms

What participants receive

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

  • Trastuzumab biosimilars(Herzuma), GedatolisibDrug

    Also called Herzuma plus Gedatolisib

    • Trastuzumab biosimilar: Intravenously administered on Day 1 of every 21 day cycle at a dose of 6mg/kg (loading dose 8mg/kg at 1C)
    • Gedatolisib: Intravenously administered on Day 1, 8 and 15 of every 21 day cycle at a dose of 180mg
Study groups in NCT03698383
Study groupRoleWhat they receive
Herzuma plus GedatolisibExperimentalNot described
Receives: Drug: Trastuzumab biosimilars(Herzuma), Gedatolisib

What is being measured

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

  1. Objective response rate

    the percentage of patients experiencing confirmed complete response (CR) and partial response (PR) assessed by RECIST criteria v.1.1

    Measured: within maximum 3 years

Secondary outcomes (2)

  1. Progression free survival

    the time from study entry until the first observation of disease progression according to the above schedule or death due to any cause

    Measured: within maximum 3 years

  2. Overall survival

    the time from study entry until death

    Measured: within maximum 3 years

Timeline

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

  1. First posted9 Oct 2018
  2. Study start3 Dec 2019
  3. Primary completionOct 2021 (estimated)
  4. Study completionDec 2021 (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
Masking
None (open label)
Enrolment
15 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03698383
Sponsor's protocol ID
KCSG-BR18-13/TR-03
Status last verified
Feb 2021
First submitted
4 Oct 2018
Last updated
18 Feb 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Harbeck N, Huang CS, Hurvitz S, Yeh DC, Shao Z, Im SA, Jung KH, Shen K, Ro J, Jassem J, Zhang Q, Im YH, Wojtukiewicz M, Sun Q, Chen SC, Goeldner RG, Uttenreuther-Fischer M, Xu B, Piccart-Gebhart M; LUX-Breast 1 study group. Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):357-366. doi: 10.1016/S1470-2045(15)00540-9. Epub 2016 Jan 26.

    PubMed 26822398

  • Wong HH, Collins J, McAdam K, Wilson C. Trastuzumab beyond progression in advanced breast cancer: national guidance versus oncologist's decision. Oncology. 2014;86(1):22-3. doi: 10.1159/000356876. Epub 2013 Dec 10. No abstract available.

    PubMed 24335099

  • Rexer BN, Arteaga CL. Optimal targeting of HER2-PI3K signaling in breast cancer: mechanistic insights and clinical implications. Cancer Res. 2013 Jul 1;73(13):3817-20. doi: 10.1158/0008-5472.CAN-13-0687. Epub 2013 Jun 21.

    PubMed 23794708

  • Wang L, Yu X, Wang C, Pan S, Liang B, Zhang Y, Chong X, Meng Y, Dong J, Zhao Y, Yang Y, Wang H, Gao J, Wei H, Zhao J, Wang H, Hu C, Xiao W, Li B. The anti-ErbB2 antibody H2-18 and the pan-PI3K inhibitor GDC-0941 effectively inhibit trastuzumab-resistant ErbB2-overexpressing breast cancer. Oncotarget. 2017 May 16;8(32):52877-52888. doi: 10.18632/oncotarget.17907. eCollection 2017 Aug 8.

    PubMed 28881779

  • Courtney KD, Corcoran RB, Engelman JA. The PI3K pathway as drug target in human cancer. J Clin Oncol. 2010 Feb 20;28(6):1075-83. doi: 10.1200/JCO.2009.25.3641. Epub 2010 Jan 19.

    PubMed 20085938

  • Del Campo JM, Birrer M, Davis C, Fujiwara K, Gollerkeri A, Gore M, Houk B, Lau S, Poveda A, Gonzalez-Martin A, Muller C, Muro K, Pierce K, Suzuki M, Vermette J, Oza A. A randomized phase II non-comparative study of PF-04691502 and gedatolisib (PF-05212384) in patients with recurrent endometrial cancer. Gynecol Oncol. 2016 Jul;142(1):62-69. doi: 10.1016/j.ygyno.2016.04.019. Epub 2016 Apr 24.

    PubMed 27103175

  • Janku F, Wheler JJ, Naing A, Falchook GS, Hong DS, Stepanek VM, Fu S, Piha-Paul SA, Lee JJ, Luthra R, Tsimberidou AM, Kurzrock R. PIK3CA mutation H1047R is associated with response to PI3K/AKT/mTOR signaling pathway inhibitors in early-phase clinical trials. Cancer Res. 2013 Jan 1;73(1):276-84. doi: 10.1158/0008-5472.CAN-12-1726. Epub 2012 Oct 12.

    PubMed 23066039

  • Baselga J, Cortes J, Im SA, Clark E, Ross G, Kiermaier A, Swain SM. Biomarker analyses in CLEOPATRA: a phase III, placebo-controlled study of pertuzumab in human epidermal growth factor receptor 2-positive, first-line metastatic breast cancer. J Clin Oncol. 2014 Nov 20;32(33):3753-61. doi: 10.1200/JCO.2013.54.5384. Epub 2014 Oct 20.

    PubMed 25332247

  • Hurvitz SA, Andre F, Jiang Z, Shao Z, Mano MS, Neciosup SP, Tseng LM, Zhang Q, Shen K, Liu D, Dreosti LM, Burris HA, Toi M, Buyse ME, Cabaribere D, Lindsay MA, Rao S, Pacaud LB, Taran T, Slamon D. Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial. Lancet Oncol. 2015 Jul;16(7):816-29. doi: 10.1016/S1470-2045(15)00051-0. Epub 2015 Jun 16.

    PubMed 26092818

  • Andre F, Hurvitz S, Fasolo A, Tseng LM, Jerusalem G, Wilks S, O'Regan R, Isaacs C, Toi M, Burris H, He W, Robinson D, Riester M, Taran T, Chen D, Slamon D. Molecular Alterations and Everolimus Efficacy in Human Epidermal Growth Factor Receptor 2-Overexpressing Metastatic Breast Cancers: Combined Exploratory Biomarker Analysis From BOLERO-1 and BOLERO-3. J Clin Oncol. 2016 Jun 20;34(18):2115-24. doi: 10.1200/JCO.2015.63.9161. Epub 2016 Apr 18.

    PubMed 27091708

  • Mauro C, Smith J, Cucchi D, Coe D, Fu H, Bonacina F, Baragetti A, Cermenati G, Caruso D, Mitro N, Catapano AL, Ammirati E, Longhi MP, Okkenhaug K, Norata GD, Marelli-Berg FM. Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4+ T Cell Differentiation via PI3K p110delta-Akt-Mediated Signals. Cell Metab. 2017 Mar 7;25(3):593-609. doi: 10.1016/j.cmet.2017.01.008. Epub 2017 Feb 9.

    PubMed 28190771

  • Roychoudhuri R, Eil RL, Restifo NP. The interplay of effector and regulatory T cells in cancer. Curr Opin Immunol. 2015 Apr;33:101-11. doi: 10.1016/j.coi.2015.02.003. Epub 2015 Feb 27.

    PubMed 25728990

  • Patton DT, Wilson MD, Rowan WC, Soond DR, Okkenhaug K. The PI3K p110delta regulates expression of CD38 on regulatory T cells. PLoS One. 2011 Mar 1;6(3):e17359. doi: 10.1371/journal.pone.0017359.

    PubMed 21390257

  • Pearce VQ, Bouabe H, MacQueen AR, Carbonaro V, Okkenhaug K. PI3Kdelta Regulates the Magnitude of CD8+ T Cell Responses after Challenge with Listeria monocytogenes. J Immunol. 2015 Oct 1;195(7):3206-17. doi: 10.4049/jimmunol.1501227. Epub 2015 Aug 26.

    PubMed 26311905

  • Crompton JG, Sukumar M, Roychoudhuri R, Clever D, Gros A, Eil RL, Tran E, Hanada K, Yu Z, Palmer DC, Kerkar SP, Michalek RD, Upham T, Leonardi A, Acquavella N, Wang E, Marincola FM, Gattinoni L, Muranski P, Sundrud MS, Klebanoff CA, Rosenberg SA, Fearon DT, Restifo NP. Akt inhibition enhances expansion of potent tumor-specific lymphocytes with memory cell characteristics. Cancer Res. 2015 Jan 15;75(2):296-305. doi: 10.1158/0008-5472.CAN-14-2277. Epub 2014 Nov 28.

    PubMed 25432172

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trastuzumab biosimilars(Herzuma), Gedatolisib in people with HER2-positive Breast Cancer and Metastatic Breast Cancer, run by Korean Cancer Study Group at 1 site in South Korea.

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 13 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 18 Feb 2021. 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 South Korea. 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?

Results are not available in the source record.

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

Contact Kyong Hwa Park, MD, PhD (+821047617651, khpark@korea.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (time frame: within maximum 3 years). 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 NCT03698383, which also lists 19 linked publications.

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 Feb 2021.

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