Pre Operative Trastuzumab in Operable Breast Cancer

NCT01785420 | Recruiting Phase 3

• 1 other identifier: TMH Project-982
• Study Type: interventional
• Target: 1,100
• Locations: 1 country
• Sites: 1

Brief Summary

Background Information and Rationale: Trastuzumab 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. Our 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. Objectives : Primary: The 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 Secondary: The safety of the pre-operative therapies including the early post operative morbidity

1. 1.Overall survival (OS) in all patients and in pathologically node positive patients.
2. 2.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.
3. 3.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

Conditions

Carcinoma Breast Stage I; HER2 Positive Breast Cancer

Keywords

Pre-operative Trastuzumab Protocol

Outcome Measures

Primary Outcomes (1)

• Disease Free Survival

  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. The 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.

  up to 5 yrs

Secondary Outcomes (3)

• Overall survival

  Up to 5 yrs

• Circulating Tumour Cells in Peripheral Blood

  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

• 4.1.3. Evaluation of the paraffin blocks for pTEN loss6-8 and p95ErbB2 truncated form of HER2

  upto 5 yrs

Study Arms (2)

Drug Trastuzumab

EXPERIMENTAL

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.

Drug: Trastuzumab

Control

PLACEBO COMPARATOR

A 90 minute intravenous infusion of saline as placebo

Drug: Placebo

Interventions

Trastuzumab DRUG

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.

Also known as: Herceptin

Drug Trastuzumab

Placebo DRUG

A 90 minute intravenous infusion of saline as placebo

Also known as: Normal saline

Control

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female subjects aged 18 years or older.
• 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)
• 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.
• LVEF within institutional range of normal as measured by MUGA or ECHO.
• Screening laboratory values within the following parameters:
• Absolute neutrophil count (ANC) ≥1.5 x 109 /L (1500/mm3)
• Platelet count ≥100 x 109/L (100,000/mm3)
• Hemoglobin ≥9.0 g/dL (90 g/L)
• Serum creatinine ≤1.5 x upper limit of normal (ULN)
• Total bilirubin ≤1.5 x ULN (\<3 ULN if Gilbert's disease) 6Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)
• x ULN

You may not qualify if:

• Bilateral breast cancer
• 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).
• Inadequately controlled hypertension (ie, systolic blood pressure \[BP\] \> 180 mm Hg or diastolic BP \> 100 mm Hg).
• 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).
• Significant chronic gastrointestinal disorder with diarrhea as a major symptom (eg, Crohn's disease, malabsorption, or grade ≥2 diarrhea of any etiology at baseline).
• Women who are pregnant, breast-feeding.

Sponsors & Collaborators

• Dr Rajendra A. Badwe: lead
• Tata Memorial Hospital: collaborator

Study Sites (1)

Tata Memorial Centre

Mumbai, 400012, India

RECRUITING

Related Publications (11)

• 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: 20142587 RESULT

• 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: 21670457 RESULT

• 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: 14734470 RESULT

• 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: 4946080 RESULT

• 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: 15324695 RESULT

• 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: 11454999 RESULT

• 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: 16404430 RESULT

• 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: 16428482 RESULT

• 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: 14737100 RESULT

• 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: 17440164 RESULT

• 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.

  PMID: 16148022 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; Saline Solution

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Rajendra A Badwe, MS

  Director and professor, Surgical Oncology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rajendra A Badwe, MS

CONTACT

91-22-21477000; badwera@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director and Professor , Surgical Oncology, Tata Memorial Hospital

Study Record Dates

• First Submitted: January 1, 2013
• First Posted: February 7, 2013
• Study Start: May 1, 2013
• Primary Completion: April 1, 2025
• Study Completion (Estimated): February 1, 2027
• Last Updated: April 9, 2025

Record last verified: 2025-04

Locations

IN (1)