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Image-guided De-escalation of Neo-adjuvant Chemotherapy in HER2-positive Breast Cancer: the TRAIN-3 Study (TRAIN-3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03820063
Recruitment Status : Recruiting
First Posted : January 29, 2019
Last Update Posted : July 10, 2020
Sponsor:
Collaborators:
Roche Pharma AG
BOOG Study Center
Information provided by (Responsible Party):
Borstkanker Onderzoek Groep

Brief Summary:
This is a multicenter, single arm, phase II study evaluating the efficacy of image-guided de-escalating neoadjuvant treatment with paclitaxel, Herceptin® (trastuzumab), carboplatin, and pertuzumab (PTC-Ptz) in stage II-Ill HER2-positive breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: PTC-Pz Phase 2

Detailed Description:

High pathological complete response (pCR)-rates are seen using different neoadjuvant chemotherapy schedules with trastuzumab and pertuzumab in HER2-positive stage II - III breast cancer patients. Total pCR rates in breast and axilla have been described as high as 64%, and with an even higher rate of >80% in patients with HER2-positive and hormone receptor (HR) negative tumors. PCR is associated with better long-term outcomes in patients with HER2-positive breast cancer. Three year progression-free survival ranges between 85-90%. Neoadjuvant treatment of HER2-positive breast cancer typically consists of six to nine cycles of treatment. Longer duration of treatment is associated with higher pCR-rates but gives more toxicity. Pathological complete responses are sometimes seen after only 10-12 days of neoadjuvant treatment. It is therefore important to investigate which patients can safely be treated with less than six cycles of chemotherapy and who requires more than six cycles for maximum activity.

The radiologic response of a breast tumor after neoadjuvant therapy is predictive of the pathologic response, although the accuracy differs between breast cancer subtypes. It is hypothesized that patients with an early complete radiologic response may not benefit from additional chemotherapy and can be referred for early surgery. Patients who have not achieved pCR after early surgery despite radiologic complete response (rCR) are candidates for further adjuvant chemotherapy to complete the initially planned number of treatment cycles and maintain maximum treatment activity. Imaged guided de-escalation in which the number of treatment cycles is determined by the radiologic response could thus reduce toxicity in neoadjuvant treatment while maintaining activity.

This study will evaluate the efficacy of image-guided de-escalation of neoadjuvant chemotherapy in patients with HER2-positive breast cancer.

To maintain efficacy, patients who do not achieve pCR will complete a total of nine cycles taxane-containing chemotherapy followed by 14 cycles of treatment with adjuvant T-DM1. Patients who achieve early pCR will continue treatment with Herceptin® and pertuzumab to complete one full year of treatment.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 462 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: neoadjuvant courses PTC-Ptz; adjuvant courses Ptz (pCR) or T-DM1 (non-pCR)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Image-guided De-escalation of Neo-adjuvant Chemotherapy in HER2-positive Breast Cancer: the TRAIN-3 Study
Actual Study Start Date : February 27, 2019
Estimated Primary Completion Date : February 1, 2022
Estimated Study Completion Date : February 1, 2032

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: PTC-Pz
  • Paclitaxel 80mg/m2 administered intravenously on day 1 and day 8
  • Herceptin® 6mg/kg administered intravenously on day 1 (loading dose 8mg/kg) or Herceptin® administered subcutaneously 600mg on day 1
  • Carboplatin AUC 6mg•ml/min administered intravenously on day 1
  • Pertuzumab 420mg administered intravenously on day 1 (loading dose 840mg)
  • Treatment cycles are repeated on day 22

Patients who do not achieve pCR will complete a total of nine cycles taxane-containing chemotherapy followed by 14 cycles of treatment with adjuvant T-DM1.

Drug: PTC-Pz
  • Paclitaxel 80mg/m2 administered intravenously on day 1 and day 8
  • Herceptin® 6mg/kg administered intravenously on day 1 (loading dose 8mg/kg) or Herceptin® administered subcutaneously 600mg on day 1
  • Carboplatin AUC 6mg•ml/min administered intravenously on day 1
  • Pertuzumab 420mg administered intravenously on day 1 (loading dose 840mg)
  • Treatment cycles are repeated on day 22

In case of non pCR; Adjuvant T-DM1, 3.6mg/kg Q 22 days, for 14 cycles.





Primary Outcome Measures :
  1. Event free survival at three years [ Time Frame: 3 years ]
    Number of patients without progression of disease recurrence, second primary or death


Secondary Outcome Measures :
  1. Overall survival at three years [ Time Frame: 3 years ]
    Number of patients alive at three years

  2. Pathologic complete response in breast and axilla [ Time Frame: an average of 6 months ]
    Number of patients with absence of invasive tumor cells in breast and axilla at surgery

  3. Radiologic complete response [ Time Frame: an average of 6 months ]
    Number of patients with absence of pathologic enhancement on MRI

  4. Number of neoadjuvant chemotherapy cycles administered [ Time Frame: an average of 1 year ]
    Number of neoadjuvant chemotherapy cycles administered per patient

  5. Number of radical and non-radical resections [ Time Frame: an average of 6 months ]
    Number of patients with radical and non-radical resections

  6. Incidence and severity of adverse events [ Time Frame: an average of 1 year ]
    Number of patients with toxicity grade >= 3 (CTCAE v5.0) until 30 days after last adjuvant administration

  7. Incidence and severity of cardiotoxicity and neuropathy [ Time Frame: an average of 1 year ]
    Number of patients with cardiotoxicity and neuropathy grade >= 2 (CTCAE v5.0) until 30 days after last adjuvant administration

  8. Incidence of symptomatic LVSD (heart failure), [ Time Frame: an average of 1 year ]
    Number of patients with an asymptomatic decline in LVEF requiring treatment or leading to discontinuation of pertuzumab and Herceptin, or a decrease ≥10 percentage points from baseline to a LVEF <50%

  9. Grade ≥3 laboratory test abnormalities [ Time Frame: an average of 1 year ]
    Number of patients with Grade ≥3 laboratory test abnormalities

  10. Incidence of number of tumor positive Vacuum Assisted Core Biopsy [ Time Frame: an average 6 months ]
    Number of patients with tumor present at Vacuum Assisted Core Biopsy at the moment of radiological complete response on MRI



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically confirmed primairy infiltrating breast cancer.
  2. Stage II or Ill disease.
  3. Overexpression and/or amplification of HER2 in an invasive component of the core biopsy.
  4. Age <:18
  5. ECOG Group performance status
  6. LVEF >50% measured by echocardiography, MRI or MUGA
  7. Known HR-status ( in percentages)

Exclusion Criteria:

  1. Previous radiation therapy of chemotherapy
  2. Pregnancy or breastfeeding
  3. Evidence of distant metastases
  4. Evidence of bilateral infiltrating breast cancer
  5. Concurrent anti-cancer treatment or another investigational drug

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03820063


Contacts
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Contact: Anna van der Voort, MD +3120512 ext 9111 a.vd.voort@nki.nl
Contact: G S Sonke, MD train3@nki.nl

Locations
Show Show 51 study locations
Sponsors and Collaborators
Borstkanker Onderzoek Groep
Roche Pharma AG
BOOG Study Center
Investigators
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Principal Investigator: G S Sonke, MD NKI-AvL
Study Director: A E van Leeuwen- Stok, PhD BOOG Study Center
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Responsible Party: Borstkanker Onderzoek Groep
ClinicalTrials.gov Identifier: NCT03820063    
Other Study ID Numbers: BOOG 2018-01
First Posted: January 29, 2019    Key Record Dates
Last Update Posted: July 10, 2020
Last Verified: July 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Borstkanker Onderzoek Groep:
neo adjuvant
HER2 positive
de-escalation
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases