Ignite Creation Date:
2025-12-25 @ 4:26 AM
Ignite Modification Date:
2026-03-03 @ 6:29 AM
Study NCT ID:
NCT01785420
Status:
RECRUITING
Last Update Posted:
2025-04-09
First Post:
2013-01-01
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Pre Operative Trastuzumab in Operable Breast Cancer
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001943', 'term': 'Breast Neoplasms'}], 'ancestors': [{'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D001941', 'term': 'Breast Diseases'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000068878', 'term': 'Trastuzumab'}, {'id': 'D000077330', 'term': 'Saline Solution'}], 'ancestors': [{'id': 'D061067', 'term': 'Antibodies, Monoclonal, Humanized'}, {'id': 'D000911', 'term': 'Antibodies, Monoclonal'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}, {'id': 'D000077324', 'term': 'Crystalloid Solutions'}, {'id': 'D007552', 'term': 'Isotonic Solutions'}, {'id': 'D012996', 'term': 'Solutions'}, {'id': 'D004364', 'term': 'Pharmaceutical Preparations'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 1100}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2013-05'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-04', 'completionDateStruct': {'date': '2027-02', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-04-08', 'studyFirstSubmitDate': '2013-01-01', 'studyFirstSubmitQcDate': '2013-02-06', 'lastUpdatePostDateStruct': {'date': '2025-04-09', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2013-02-07', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2025-04', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Disease Free Survival', 'timeFrame': 'up to 5 yrs', 'description': 'Survival follow-up visits (or information Collected via telephone call) will be conducted approximately every 6 months (ie, 24 weeks) starting from the last day of primary (adjuvant) treatment.\n\nThe subject will be called at clinic and will be carefully examined by a member of study team. A mammogram will be done every 18 months. If patient is symptomatic,additional investigations will be performed. Subject status as alive, alive with disease will be documented in the source file.'}], 'secondaryOutcomes': [{'measure': 'Overall survival', 'timeFrame': 'Up to 5 yrs', 'description': '4.1.1. Overall survival (OS) in all patients and in pathologically node positive patients.'}, {'measure': 'Circulating Tumour Cells in Peripheral Blood', 'timeFrame': '1. before starting pre-operative therapy and at the same time point in the control arm. 2. 10 minutes prior to start of surgery. 3. During surgery . 4. 10 days after surgery'}, {'measure': '4.1.3. Evaluation of the paraffin blocks for pTEN loss6-8 and p95ErbB2 truncated form of HER2', 'timeFrame': 'upto 5 yrs'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Pre-operative Trastuzumab Protocol'], 'conditions': ['Carcinoma Breast Stage I', 'HER2 Positive Breast Cancer']}, 'referencesModule': {'references': [{'pmid': '20142587', 'type': 'RESULT', 'citation': 'Burstein HJ, Sun Y, Dirix LY, Jiang Z, Paridaens R, Tan AR, Awada A, Ranade A, Jiao S, Schwartz G, Abbas R, Powell C, Turnbull K, Vermette J, Zacharchuk C, Badwe R. Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer. J Clin Oncol. 2010 Mar 10;28(8):1301-7. doi: 10.1200/JCO.2009.25.8707. Epub 2010 Feb 8.'}, {'pmid': '21670457', 'type': 'RESULT', 'citation': 'Badwe R, Hawaldar R, Parmar V, Nadkarni M, Shet T, Desai S, Gupta S, Jalali R, Vanmali V, Dikshit R, Mittra I. Single-injection depot progesterone before surgery and survival in women with operable breast cancer: a randomized controlled trial. J Clin Oncol. 2011 Jul 20;29(21):2845-51. doi: 10.1200/JCO.2010.33.0738. Epub 2011 Jun 13.'}, {'pmid': '14734470', 'type': 'RESULT', 'citation': 'Ismail MS, Wynendaele W, Aerts JL, Paridaens R, Gaafar R, Shakankiry N, Khaled HM, Christiaens MR, Wildiers H, Omar S, Vandekerckhove P, Van Oosterom AT. Detection of micrometastatic disease and monitoring of perioperative tumor cell dissemination in primary operable breast cancer patients using real-time quantitative reverse transcription-PCR. Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):196-201. doi: 10.1158/1078-0432.ccr-0515-2.'}, {'pmid': '4946080', 'type': 'RESULT', 'citation': 'Nissen-Meyer R, Kjellgren K, Mansson B. Preliminary report from the Scandinavian adjuvant chemotherapy study group. Cancer Chemother Rep. 1971 Dec;55(5):561-6. No abstract available.'}, {'pmid': '15324695', 'type': 'RESULT', 'citation': 'Nagata Y, Lan KH, Zhou X, Tan M, Esteva FJ, Sahin AA, Klos KS, Li P, Monia BP, Nguyen NT, Hortobagyi GN, Hung MC, Yu D. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell. 2004 Aug;6(2):117-27. doi: 10.1016/j.ccr.2004.06.022.'}, {'pmid': '11454999', 'type': 'RESULT', 'citation': 'Depowski PL, Rosenthal SI, Ross JS. Loss of expression of the PTEN gene protein product is associated with poor outcome in breast cancer. Mod Pathol. 2001 Jul;14(7):672-6. doi: 10.1038/modpathol.3880371.'}, {'pmid': '16404430', 'type': 'RESULT', 'citation': 'Fujita T, Doihara H, Kawasaki K, Takabatake D, Takahashi H, Washio K, Tsukuda K, Ogasawara Y, Shimizu N. PTEN activity could be a predictive marker of trastuzumab efficacy in the treatment of ErbB2-overexpressing breast cancer. Br J Cancer. 2006 Jan 30;94(2):247-52. doi: 10.1038/sj.bjc.6602926.'}, {'pmid': '16428482', 'type': 'RESULT', 'citation': 'Saez R, Molina MA, Ramsey EE, Rojo F, Keenan EJ, Albanell J, Lluch A, Garcia-Conde J, Baselga J, Clinton GM. p95HER-2 predicts worse outcome in patients with HER-2-positive breast cancer. Clin Cancer Res. 2006 Jan 15;12(2):424-31. doi: 10.1158/1078-0432.CCR-05-1807.'}, {'pmid': '14737100', 'type': 'RESULT', 'citation': 'Xia W, Liu LH, Ho P, Spector NL. Truncated ErbB2 receptor (p95ErbB2) is regulated by heregulin through heterodimer formation with ErbB3 yet remains sensitive to the dual EGFR/ErbB2 kinase inhibitor GW572016. Oncogene. 2004 Jan 22;23(3):646-53. doi: 10.1038/sj.onc.1207166.'}, {'pmid': '17440164', 'type': 'RESULT', 'citation': 'Scaltriti M, Rojo F, Ocana A, Anido J, Guzman M, Cortes J, Di Cosimo S, Matias-Guiu X, Ramon y Cajal S, Arribas J, Baselga J. Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. J Natl Cancer Inst. 2007 Apr 18;99(8):628-38. doi: 10.1093/jnci/djk134.'}, {'pmid': '16148022', 'type': 'RESULT', 'citation': 'Goldhirsch A, Glick JH, Gelber RD, Coates AS, Thurlimann B, Senn HJ; Panel members. Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol. 2005 Oct;16(10):1569-83. doi: 10.1093/annonc/mdi326. Epub 2005 Sep 7.'}]}, 'descriptionModule': {'briefSummary': 'Background Information and Rationale:\n\nTrastuzumab is a humanized monoclonal antibody that acts extracellularly on the erbB-2 receptor.Trastuzumab is a recombinant humanized IgG1 monoclonal antibody against the human epidermal growth factor receptor 2 (HER2/erbB-2),which has shown in both in vitro assays and in animals, to inhibit the proliferation of human tumour cells that overexpress erbB-2. Additionally, trastuzumab is a potent mediator of antibody-dependent cell-mediated cytotoxicity (ADCC). In vitro, trastuzumab-mediated ADCC has been shown to be preferentially exerted on erbB-2 overexpressing cancer cells compared with cancer cells that do not overexpress erbB-2. Trastuzumab has emerged as a widely accepted standard of care for erbB-2-positive disease. (Metastatic/ adjuvant/neoadjuvant.\n\nOur current hypothesis suggests that the cells which are disseminated at the time of surgery will encounter an inhospitable environment which will be anti-HER in nature. Therefore combining the above mentioned streams of thought, we would like to assess the effect of a short pre-operative course of Trastuzumab on breast cancer relapse. The study is proposed in HER2 positive patients with operable breast cancer.\n\nObjectives :\n\nPrimary:\n\nThe primary objective of the study is to see the effect of short duration of peri-operative Trastuzumab on disease-free survival in comparison in all patients\n\nSecondary:\n\nThe safety of the pre-operative therapies including the early post operative morbidity\n\n1. Overall survival (OS) in all patients and in pathologically node positive patients.\n2. The level of circulating tumor cells (CTCs) in the peripheral blood assessed before starting pre-operative therapy and at the same time point in the control arm, level of CTCs 10 minutes prior to start of surgery, during surgery and 10 days after surgery on 40 consecutive consenting patients (20 in each arm). The levels of circulating chromatin will also be estimated at the same time points as CTC for these 40 patients.\n3. Evaluation of the paraffin blocks for pTEN loss6-8 and p95ErbB2 truncated form of HER2 on 100 consecutive consenting patients (50 in each arm).9-11\n\nStudy Design :\n\nThis is phase 3, randomized Double blinded parallel group study of Trastuzumab in pre operative setting in operable breast cancer patients.\n\nApproximately 1000 patients with Women with HER2neu positive, T1/T2/T3 and N0/N1. clinical T4 and/or N2 disease who are considered operable by the treating surgeon with histopathological diagnosis on core biopsies, will be included in the study. Patients with T4 or N2 (locally advanced and large operable for neo-adjuvant chemotherapy) will not be included. All node positive patients will receive single injection of Depot Inj. Progesterone 500 mg deep IM 4 -14 days prior to surgery\n\nPatients will be stratified, before randomization for Tumor size, menopausal status, and affordability for Trastuzumab and centre of the study. These patients will then be randomized 1:1 to receive the following\n\nIntervention arm: .A single dose of Trastuzumab (Herceptin, Hoffman La Roche) at 8 mg/Kg as a 90 minute intravenous infusion in 250 ml of normal saline, in the window period of 10-15 4 to 14 days (both days inclusive) prior to the planned date of surgery.\n\nControl arm: A 90 minute intravenous infusion of saline as placebo\n\nAll patients will thereafter receive standard post-operative adjuvant therapy as per local institutional practice including hormonal therapy, chemotherapy and radiation therapy.'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:a.\n\n1. Female subjects aged 18 years or older.\n2. Histologically and/or cytologically confirmed diagnosis of breast cancer. Clinical stages breast cancer: HER2 positive, T1 or T2 or T3, N0 or N1, resectable T4, or resectable N2, (all M0)\n3. Documentation of erbB-2 gene amplification by FISH (as defined by a ratio \\>2.2) or chromogenic in situ hybridization (CISH, as defined by the manufacturer's kit instruction) or documentation of erbB-2-overexpression by IHC (defined as IHC3+, or IHC2+ with FISH or CISH confirmation) based on local laboratory.\n4. LVEF within institutional range of normal as measured by MUGA or ECHO.\n5. Screening laboratory values within the following parameters:\n\n 1. Absolute neutrophil count (ANC) ≥1.5 x 109 /L (1500/mm3)\n 2. Platelet count ≥100 x 109/L (100,000/mm3)\n 3. Hemoglobin ≥9.0 g/dL (90 g/L)\n 4. Serum creatinine ≤1.5 x upper limit of normal (ULN)\n 5. Total bilirubin ≤1.5 x ULN (\\<3 ULN if Gilbert's disease) 6Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)\n\n * 2.5 x ULN\n\nExclusion Criteria:\n\n1. Bilateral breast cancer\n2. Active uncontrolled cardiac disease, including cardiomyopathy, CHF (New York Heart Association \\[NYHA\\] functional classification of ≥3), unstable angina, and myocardial infarction (within 12 months of study entry).\n3. Inadequately controlled hypertension (ie, systolic blood pressure \\[BP\\] \\> 180 mm Hg or diastolic BP \\> 100 mm Hg).\n4. Family history of congenital long or short QT syndrome, Brugada syndrome or QT/QTc interval \\> 0.45 second or known history of QT/QTc prolongation or torsade de pointe (TdP).\n5. Significant chronic gastrointestinal disorder with diarrhea as a major symptom (eg, Crohn's disease, malabsorption, or grade ≥2 diarrhea of any etiology at baseline).\n6. Women who are pregnant, breast-feeding."}, 'identificationModule': {'nctId': 'NCT01785420', 'briefTitle': 'Pre Operative Trastuzumab in Operable Breast Cancer', 'organization': {'class': 'OTHER_GOV', 'fullName': 'Tata Memorial Hospital'}, 'officialTitle': 'A Phase III Double Blind Randomized Placebo Controlled Study of Trastuzumab as Short Duration Preoperative Therapy in Patients With HER2-neu Positive Operable Breast Cancer', 'orgStudyIdInfo': {'id': 'TMH Project-982'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Drug Trastuzumab', 'description': 'A single dose of Trastuzumab (Herceptin, Hoffman La Roche) at 8 mg/Kg as a 90 minute infusion in 250 ml of normal saline, in the window period of 14 days (both days inclusive) prior to the planned date of surgery.', 'interventionNames': ['Drug: Trastuzumab']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Control', 'description': 'A 90 minute intravenous infusion of saline as placebo', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Trastuzumab', 'type': 'DRUG', 'otherNames': ['Herceptin'], 'description': 'A single dose of Trastuzumab (Herceptin, Hoffman La Roche) at 8 mg/Kg as a 90 minute infusion in 250 ml of normal saline, in the window period of 14 days (both days inclusive) prior to the planned date of surgery.', 'armGroupLabels': ['Drug Trastuzumab']}, {'name': 'Placebo', 'type': 'DRUG', 'otherNames': ['Normal saline'], 'description': 'A 90 minute intravenous infusion of saline as placebo', 'armGroupLabels': ['Control']}]}, 'contactsLocationsModule': {'locations': [{'zip': '400012', 'city': 'Mumbai', 'status': 'RECRUITING', 'country': 'India', 'contacts': [{'name': 'Rajendra A Badwe, MS', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Tata Memorial Centre', 'geoPoint': {'lat': 19.07283, 'lon': 72.88261}}], 'centralContacts': [{'name': 'Rajendra A Badwe, MS', 'role': 'CONTACT', 'email': 'badwera@gmail.com', 'phone': '91-22-21477000', 'phoneExt': '4265'}], 'overallOfficials': [{'name': 'Rajendra A Badwe, MS', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Director and professor, Surgical Oncology'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Dr Rajendra A. Badwe', 'class': 'OTHER_GOV'}, 'collaborators': [{'name': 'Tata Memorial Hospital', 'class': 'OTHER_GOV'}], 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Director and Professor , Surgical Oncology, Tata Memorial Hospital', 'investigatorFullName': 'Dr Rajendra A. Badwe', 'investigatorAffiliation': 'Tata Memorial Hospital'}}}}