Clinical Trial to Assess Pharmacokinetic Parameters and Safety of NNG-TMAB (Trastuzumab) on Recurrent or Metastatic Breast Cancer Patients.

NCT05301530 | Completed Phase 1 DMC

• 1 other identifier: NNG17.1
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

Targeted therapy in the treatment of breast cancer targets HER2 receptor (Human Epidermal growth factor Receptor). HER2 receptor plays an important role in cell growth and differentiation (5). However, when HER2 overexpresses, it may lead to cancer. HER2 positive malignance exacerbates pathology and worsens clinical outcome, such as shortened overall survival (OS) compared with non-HER2 overexpression patients (6), (7). About 20-30% overexpression HER2/neogene breast cancer patients and patients having HER2 overexpression tumor have disease progression and poor prognosis in metastatic process (8), (9). Currently, targeted therapeutic, which attaches to the HER2 receptor, inhibiting the growth of cancer cells has been approved. One of these products is Trastuzumab. The study processed on 50 females aged between 18 and 65, recurrent or metastatic breast cancer patients with positive HER2. The subjects were randomly distributed in 2 groups as NNG-TMAB + docetaxel or Herceptin® + docetaxel, in blocks of 4 in a 1:1 ratio (NNG-TMAB: Herceptin®). In each block of 4 will be 2 patients in the experimental group and 2 patients in the control group. Primary endpoint is serum peak concentrations (Cmax), area under the curve from 0 to t (AUC0-t). This trial is intended to assess the biosimilarity of pharmacokinetic parameters, safety between Faceptor (experimental drug) and Herceptin (reference).

Conditions

Breast Cancer Metastatic; Breast Cancer Female; Breast Cancer Recurrent

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetic parameters: Cmax

  Serum peak concentrations (Cmax)

  Blood samples will be collected at following time points: prior to IP administration; 1.5; 3; 4.5; 6; 24; 96; 168; 336 and 504 hours after inject drug cycle 1

• Pharmacokinetic parameters: AUC0-t

  Area under the curve from 0 to t (AUC0-t)

  Blood samples will be collected at following time points: prior to IP administration; 1.5; 3; 4.5; 6; 24; 96; 168; 336 and 504 hours after inject drug cycle 1

Secondary Outcomes (5)

• Pharmacokinetic parameters: Ctrough

  Blood samples will be collected at following time points: day 23rd, 65th, 107th and 128th (at the beginning of visits 4, 8, 12, 14)

• Pharmacokinetic parameters: AUC0-∞

  Blood samples will be collected at following time points: prior to IP administration; 1.5; 3; 4.5; 6; 24; 96; 168; 336 and 504 hours after inject drug cycle 1

• Pharmacokinetic parameters: Tmax

  Blood samples will be collected at following time points: prior to IP administration; 1.5; 3; 4.5; 6; 24; 96; 168; 336 and 504 hours after inject drug cycle 1

• Pharmacokinetic parameters: T1/2

  Blood samples will be collected at following time points: prior to IP administration; 1.5; 3; 4.5; 6; 24; 96; 168; 336 and 504 hours after inject drug cycle 1

• Rate of AE and SAE occurence

  up to 128 days (6 cycles - each cycle is 21 days)

Study Arms (2)

Faceptor + Docetacel

EXPERIMENTAL

Patients received a loading dose of Faceptor 8 mg/kg IV + docetaxel 75 mg/m\^2 IV on Cycle 1 followed by Faceptor 6 mg/kg IV + docetaxel 75 mg/m\^2 IV on the next 5 cycles (each cycle is 21 days)

Drug: Faceptor; Drug: Docetaxel

Herceptin + Docetacel

ACTIVE COMPARATOR

Patients received a loading dose of Herceptin 8 mg/kg IV + docetaxel 75 mg/m\^2 IV on Cycle 1 followed by Herceptin 6 mg/kg IV + docetaxel 75 mg/m\^2 IV on the next 5 cycles (each cycle is 21 days)

Drug: Herceptin; Drug: Docetaxel

Interventions

Faceptor DRUG

NNG-TMAB (trastuzumab) 150 mg, 440 mg, lyophilized power for injection, manufacturered by Nanogen Pharmaceutical Biotechnology JSC.

Also known as: NNG-TMAB, Trastazumab

Faceptor + Docetacel

Herceptin DRUG

Herceptin (trastuzumab) 150mg, 440mg, powder for concentrate for solution, manufactured by Roche.

Also known as: Trastuzumab

Herceptin + Docetacel

Docetaxel DRUG

The drug Docetaxel in this study has the brand name Taxotere manufactured by Sanofi company.

Also known as: Taxotere

Faceptor + Docetacel; Herceptin + Docetacel

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients from 18 to 65 years old.
• Willing to give written and signed informed consent.
• Have pathologically or cytologically confirmed breast cancer.
• Inoperable, recurrent or metastatic breast cancer according to TNM classification and investigator' s assessment.
• Presence of at least 1 tumour with a size not less than 1 cm (revealed with computed tomography (CT) slice thickness not more than 5 mm). Patients having bone metastasis as the only measurable tumour are not eligible for the trial.
• Grade 3+ HER2 overexpression confirmed by immunohistochemical (IHC) staining or grade 2+ HER2 overexpression accompanied by HER2 gene amplification confirmed by fluorescent hybridization in situ (FISH).
• Eastern Cooperative oncology group performance status ≤ 2
• Willing to comply the requirements of the study protocol.
• Have a survival expectancy of at least 6 months.
• At screening period: Hb ≥ 9 g/dL; Neutrophils ≥ 1,5x10\^9/L; platelets ≥ 100x10\^9/L; creatinine level ≤ 1,5 x upper limit of normal (ULN); bilirubin level \< 1,5 x ULN; ALT/AST \< 2,5 x ULN (\< 5 x ULN for patients with liver metastases), ALP \< 5 x ULN.

You may not qualify if:

• Previous anticancer therapy for metastatic BC, including previous anticancer therapy with signal transduction inhibitors (e.g. lapatinib), biological drugs (e.g. trastuzumab, bevacizumab), experimental (not approved for BC therapy) anticancer drugs. Any previous chemotherapy or hormonal therapy is allowed.
• Previously treated with doxorubicin \> 400 mg/m2; epirubicin \> 800 mg/m2 in accumulative dosages.
• Surgery, radiation therapy, use of any experimental medications within 4 weeks prior to randomization.
• Clinical evidence or X-ray show that breast cancer metastases in central nervous system
• Patients with metastatic tumor to the bone is the only tumor to be measured
• Systolic blood pressure \>150mmHg and/or diastolic blood pressure \>100mmHg. Uncontrolled hypertension comprising all cases of arterial hypertension when no decrease in blood pressure could be achieved despite treatment with a combination of 3 antihypertensive drugs including one diuretic and non-medicamental correction methods (low salt diet, physical exercise)
• Cardiovascular system pathology (congestive heart failure (CHF) stage III-IV according to New York Heart Association (NYHA) classification, unstable angina pectoris, myocardial infarction) within 12 months prior to randomization. LVEF \< 50% according to echocardiogram when screening.
• Acute or chronic infection (except for acute or chronic infection that is stable and does not affect the study evaluation). Infecting HIV, HBV or HCV, Syphilis
• Patients with a history of severe allergic reaction to trastuzumab, paclitaxel, docetaxel or other ingredients in the formulation
• The patient has evidence of a serious illness (such as resting dyspnea or severe lung disease, etc.) or an abnormal laboratory test that, in the judgment of the researcher, will affect participation. research and completion of patient research, or may affect the patient's response evaluation.
• Pregnancy, intend to get pregnant, lactation

Sponsors & Collaborators

• Nanogen Pharmaceutical Biotechnology Joint Stock Company: lead
• Vietstar Biomedical Research: collaborator
• MedProve Inc: collaborator

Study Sites (2)

19-8 Hospital

Hanoi, Vietnam

Location

HCMC Oncology Hospital

Ho Chi Minh City, Vietnam

Location

Related Publications (31)

• Các liệu pháp nhắm trúng đích nở rộ, Nguyễn Chấn Hùng và cộng sự, Tạp chí Ung thư học Việt Nam, số 4 - 2013

  BACKGROUND

• Bell R. What can we learn from Herceptin trials in metastatic breast cancer? Oncology. 2002;63 Suppl 1:39-46. doi: 10.1159/000066200.

  PMID: 12422054 BACKGROUND

• Hamberg P, Bos MM, Braun HJ, Stouthard JM, van Deijk GA, Erdkamp FL, van der Stelt-Frissen IN, Bontenbal M, Creemers GJ, Portielje JE, Pruijt JF, Loosveld OJ, Smit WM, Muller EW, Schmitz PI, Seynaeve C, Klijn JG; Dutch Breast Cancer Trialists' Group (BOOG). Randomized phase II study comparing efficacy and safety of combination-therapy trastuzumab and docetaxel vs. sequential therapy of trastuzumab followed by docetaxel alone at progression as first-line chemotherapy in patients with HER2+ metastatic breast cancer: HERTAX trial. Clin Breast Cancer. 2011 Apr;11(2):103-13. doi: 10.1016/j.clbc.2011.03.003. Epub 2011 Apr 11.

  PMID: 21569996 BACKGROUND

• Bullock K, Blackwell K. Clinical efficacy of taxane-trastuzumab combination regimens for HER-2-positive metastatic breast cancer. Oncologist. 2008 May;13(5):515-25. doi: 10.1634/theoncologist.2007-0204.

  PMID: 18515736 RESULT

• Slamon DJ, Romond EH, Perez EA; CME Consultants, Inc. Advances in adjuvant therapy for breast cancer. Clin Adv Hematol Oncol. 2006 Mar;4(3 Suppl 7):suppl 1, 4-9; discussion suppl 10; quiz 2 p following suppl 10.

  PMID: 16736568 RESULT

• Polychemotherapy for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group. Lancet. 1998 Sep 19;352(9132):930-42.

  PMID: 9752815 RESULT

• Gennari A, Conte P, Rosso R, Orlandini C, Bruzzi P. Survival of metastatic breast carcinoma patients over a 20-year period: a retrospective analysis based on individual patient data from six consecutive studies. Cancer. 2005 Oct 15;104(8):1742-50. doi: 10.1002/cncr.21359.

  PMID: 16149088 RESULT

• Hynes NE, Stern DF. The biology of erbB-2/neu/HER-2 and its role in cancer. Biochim Biophys Acta. 1994 Dec 30;1198(2-3):165-84. doi: 10.1016/0304-419x(94)90012-4. No abstract available.

  PMID: 7819273 RESULT

• Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987 Jan 9;235(4785):177-82. doi: 10.1126/science.3798106.

  PMID: 3798106 RESULT

• Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989 May 12;244(4905):707-12. doi: 10.1126/science.2470152.

  PMID: 2470152 RESULT

• Press MF, Bernstein L, Thomas PA, Meisner LF, Zhou JY, Ma Y, Hung G, Robinson RA, Harris C, El-Naggar A, Slamon DJ, Phillips RN, Ross JS, Wolman SR, Flom KJ. HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas. J Clin Oncol. 1997 Aug;15(8):2894-904. doi: 10.1200/JCO.1997.15.8.2894.

  PMID: 9256133 RESULT

• Herceptin [package insert] Roche Inc; 2010

  RESULT

• Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Anton A, Lluch A, Kennedy J, O'Byrne K, Conte P, Green M, Ward C, Mayne K, Extra JM. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005 Jul 1;23(19):4265-74. doi: 10.1200/JCO.2005.04.173. Epub 2005 May 23.

  PMID: 15911866 RESULT

• Meden H, Beneke A, Hesse T, Novophashenny I, Wischnewsky M. Weekly intravenous recombinant humanized anti-P185HER2 monoclonal antibody (herceptin) plus docetaxel in patients with metastatic breast cancer: a pilot study. Anticancer Res. 2001 Mar-Apr;21(2B):1301-5.

  PMID: 11396203 RESULT

• Plosker GL, Keam SJ. Trastuzumab: a review of its use in the management of HER2-positive metastatic and early-stage breast cancer. Drugs. 2006;66(4):449-75. doi: 10.2165/00003495-200666040-00005.

  PMID: 16597163 RESULT

• Meza-Junco J, Au HJ, Sawyer MB. Trastuzumab for gastric cancer. Expert Opin Biol Ther. 2009 Dec;9(12):1543-51. doi: 10.1517/14712590903439702.

  PMID: 19916733 RESULT

• Lara PN Jr, Chee KG, Longmate J, Ruel C, Meyers FJ, Gray CR, Edwards RG, Gumerlock PH, Twardowski P, Doroshow JH, Gandara DR. Trastuzumab plus docetaxel in HER-2/neu-positive prostate carcinoma: final results from the California Cancer Consortium Screening and Phase II Trial. Cancer. 2004 May 15;100(10):2125-31. doi: 10.1002/cncr.20228.

  PMID: 15139054 RESULT

• Tedesco KL, Thor AD, Johnson DH, Shyr Y, Blum KA, Goldstein LJ, Gradishar WJ, Nicholson BP, Merkel DE, Murrey D, Edgerton S, Sledge GW Jr. Docetaxel combined with trastuzumab is an active regimen in HER-2 3+ overexpressing and fluorescent in situ hybridization-positive metastatic breast cancer: a multi-institutional phase II trial. J Clin Oncol. 2004 Mar 15;22(6):1071-7. doi: 10.1200/JCO.2004.10.046.

  PMID: 15020608 RESULT

• Bines J, Murad A et al. (2003), Weekly docetaxel (Docetaxel) and trastuzumab (Herceptin) as primary therapy in stage III, HER2 overexpressing breast cancer - a Brazilian multicenter study. Breast cancer Res Treat, 82 (suppl 1):S56

  RESULT

• J. McCain,

  RESULT

• Pivot X, Romieu G, Debled M, Pierga JY, Kerbrat P, Bachelot T, Lortholary A, Espie M, Fumoleau P, Serin D, Jacquin JP, Jouannaud C, Rios M, Abadie-Lacourtoisie S, Tubiana-Mathieu N, Cany L, Catala S, Khayat D, Pauporte I, Kramar A; PHARE trial investigators. 6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial. Lancet Oncol. 2013 Jul;14(8):741-8. doi: 10.1016/S1470-2045(13)70225-0. Epub 2013 Jun 11.

  PMID: 23764181 RESULT

• Bùi Diệu (2003), "Ung thư vú, thực hành xạ trị ung thư", Nhà xuất bản Y học, 278-295

  RESULT

• Tô Anh Dũng (1996), "Đặc điểm lâm sàng ung thư biểu mô tuyến vú và đánh giá một số yếu tố (1987-1990)", luận văn tốt nghiệp Thạc sĩ Y học, Trường Đại học Y Hà Nội

  RESULT

• Vũ Hồng Thằng, Đỗ Anh Tú, Nguyễn Thị Thái Hòa, Vũ Quang Toản (2010), "Phân tích giá trị tiên lượng yếu tố phát triển biểu mô trong bệnh ung thư vú phụ nữ", Tạp chí ung thư học 2010, 448-452

  RESULT

• Wardley AM, Pivot X, Morales-Vasquez F, Zetina LM, de Fatima Dias Gaui M, Reyes DO, Jassem J, Barton C, Button P, Hersberger V, Torres AA. Randomized phase II trial of first-line trastuzumab plus docetaxel and capecitabine compared with trastuzumab plus docetaxel in HER2-positive metastatic breast cancer. J Clin Oncol. 2010 Feb 20;28(6):976-83. doi: 10.1200/JCO.2008.21.6531. Epub 2009 Dec 28.

  PMID: 20038734 RESULT

• Herzuma - Public Assessment summary information for Biosimilar

  RESULT

• American Cancer Society. Breast Cancer Facts & Figures 2013-2014. Atlanta: American Cancer Society, Inc. 2013

  RESULT

• Harvey V, Mouridsen H, Semiglazov V, Jakobsen E, Voznyi E, Robinson BA, Groult V, Murawsky M, Cold S. Phase III trial comparing three doses of docetaxel for second-line treatment of advanced breast cancer. J Clin Oncol. 2006 Nov 1;24(31):4963-70. doi: 10.1200/JCO.2005.05.0294. Epub 2006 Oct 10.

  PMID: 17033039 RESULT

• Chan S, Friedrichs K, Noel D, Pinter T, Van Belle S, Vorobiof D, Duarte R, Gil Gil M, Bodrogi I, Murray E, Yelle L, von Minckwitz G, Korec S, Simmonds P, Buzzi F, Gonzalez Mancha R, Richardson G, Walpole E, Ronzoni M, Murawsky M, Alakl M, Riva A, Crown J; 303 Study Group. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol. 1999 Aug;17(8):2341-54. doi: 10.1200/JCO.1999.17.8.2341.

  PMID: 10561296 RESULT

• Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, Utriainen T, Turpeenniemi-Hujanen T, Jyrkkio S, Moykkynen K, Helle L, Ingalsuo S, Pajunen M, Huusko M, Salminen T, Auvinen P, Leinonen H, Leinonen M, Isola J, Kellokumpu-Lehtinen PL. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer Trial. J Clin Oncol. 2009 Dec 1;27(34):5685-92. doi: 10.1200/JCO.2008.21.4577. Epub 2009 Nov 2.

  PMID: 19884557 RESULT

• Baselga J, Carbonell X, Castaneda-Soto NJ, Clemens M, Green M, Harvey V, Morales S, Barton C, Ghahramani P. Phase II study of efficacy, safety, and pharmacokinetics of trastuzumab monotherapy administered on a 3-weekly schedule. J Clin Oncol. 2005 Apr 1;23(10):2162-71. doi: 10.1200/JCO.2005.01.014.

  PMID: 15800309 RESULT

Related Links

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MeSH Terms

Interventions

Trastuzumab; Docetaxel

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two group: study drug and reference

Study Record Dates

• First Submitted: June 8, 2020
• First Posted: March 29, 2022
• Study Start: May 27, 2019
• Primary Completion: August 31, 2020
• Study Completion: February 19, 2021
• Last Updated: March 29, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

VN (2)