Unraveling KAdcyla Resistance In Human Epidermal Growth Factor Receptor 2(HER2) Positive Advanced Breast Cancer (KATIA)

NCT03829306 | Completed

• 1 other identifier: GEICAM/2017-04
• Study Type: observational
• Target: 32
• Locations: 1 country
• Sites: 10

Brief Summary

The study aim is to perform a comprehensive and integrated characterization of mechanisms of primary and acquired resistance to Kadcyla in a prospective cohort of progressive/recurrent HER2-positive breast cancer patients.

Conditions

Advanced Breast Cancer

Keywords

HER2-positive

Outcome Measures

Primary Outcomes (2)

• Genomic alterations on tumor samples with Objective Response (OR) to Kadcyla

  Genomic alterations at baseline Formalin-Fixed Paraffin-Embedded (FFPE) tumor samples (primary tumor or metastatic sample) will be analysed by F-One. This test provides information about genomic alterations (base substitutions, insertions/deletions, copy number variations and rearrangements) in 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer (https://foundationone.com/docs/FoundationOne). OR (complete response plus partial response) will be measured in tumor assessments performed approximately every 3 cycles, based on the investigator assessment according to the standard institutional guidelines using RECIST version 1.1.

  Estimated median of 12 months (until disease progression is confirmed)

• Tumor-specific mutation in plasma samples with OR to Kadcyla

  Tumor-specific mutation identification will be measured by the test Foundation ACT (F-ACT) on plasma samples collected at baseline and at progression.This test probes 62 cancer-related genes across the 4 classes of genomic alterations (https://www.foundationmedicine.com/genomic-testing/foundation-act). OR (complete response plus partial response) will be measured in tumor assessments performed approximately every 3 cycles, based on the investigator assessment according to the standard institutional guidelines using RECIST version 1.1.

  Estimated median of 12 months (until disease progression is confirmed)

Secondary Outcomes (7)

• Genomic alterations on tumor samples with progression-free survival (PFS)

  Estimated median of 12 months (until disease progression is confirmed)

• Tumor-specific mutation in plasma samples with progression-free survival (PFS)

  Estimated median of 12 months (until disease progression is confirmed)

• Genomic alterations on tumor samples with Progression-free survival

  Estimated median of 12 months (until disease progression is confirmed)

• Genomic alterations on tumor samples with Time to Progression (TTP)

  Estimated median of 12 months (until disease progression is confirmed)

• Tumor-specific mutation in plasma samples with Progression-free survival

  Estimated median of 12 months (until disease progression is confirmed)

Other Outcomes (7)

• Genomic alterations on tumor samples correlation with overall survival (OS)

  Estimated median of 12 months (until disease progression is confirmed)

• Tumor-specific mutation in plasma samples with overall survival (OS)

  Estimated median of 12 months (until disease progression is confirmed)

• Tumor-specific mutation in plasma samples during Kadcyla treatment with clinical benefit to the subsequent lines of therapy in terms of PFS and TTP.

  Estimated median of 12 months (until disease progression is confirmed)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The target population for inclusion in this study is HER2-positive Advanced Breast Cancer patients who are planned to be treated with Kadcyla whithin the approved indication in Spain.

You may qualify if:

• \- Patients are eligible to be included in the study only if they meet all of the following criteria and according to the corresponding Summary of Product Characteristics (SmPC):
• The patient has signed and dated the informed consent form (ICF) and it has been obtained before conducting any study specific procedure.
• Female or male patients ≥ 18 years of age on day of signing informed consent.
• Documented HER2-positive breast cancer based on local laboratory determination (preferably assessed on the most recent tumor biopsy available).
• Patients with evidence of advanced disease not amenable to resection or radiation therapy with curative intent who are planned to receive Kadcyla within the approved indication in Spain: as a single agent for the treatment of adult patients with HER2-positive, unresectable locally advanced or metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either:
• Received prior therapy for locally advanced or metastatic disease, or
• Developed disease recurrence during or within six months of completing adjuvant therapy
• Presence of measurable disease according to RECIST 1.1 for assessment of tumor response.
• Availability of tumor tissue sample from the primary tumor and/or the recurrence/metastatic site. Effort will be made to obtain a biopsy from a metastatic site in easily accessible tissues.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
• Patient must have a life expectancy ≥16 weeks.
• Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI-CTCAE v5.0 Grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator´s discretion).
• Negative serum pregnancy test result for women of childbearing potential and for women who have experienced menopause onset \< 12 months prior to study entry.
• Willingness and ability to comply with the protocol for the duration of the study including tumor and blood sample collection and undergoing the standard medical practice visits.

You may not qualify if:

• Patients will be excluded from the study if they meet any of the following criteria and according to the corresponding Summary of Product Characteristics (SmPC):
• Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons), within 3 weeks prior to study entry (or a longer period depending on the defined characteristics of the agents used).
• Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. Patients with brain metastases may be eligible for the study only if more than 4 weeks elapsed from treatment completion for these metastases (including radiation and/or surgery) and are clinically stable at the time of study entry.
• Major surgical procedure unrelated to breast cancer or significant traumatic injury within 28 days prior to study entry or anticipation of the need for major surgery during the period of Kadcyla administration.
• To present contraindications for the treatment with Kadcyla according to the corresponding Summary of Product Characteristics (SmPC).
• Known hypersensitivity to Kadcyla, excipients and/or murine proteins.
• Pregnancy or breast feeding women.
• Persistent toxicities ( NCI-CTCAE v 5.0 grade 2) caused by previous cancer therapy (except alopecia or other toxicities not considered a safety risk for the patient at investigator´s discretion).
• Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
• Known active liver disease, for example, due to hepatitis viruses B (HBV), hepatitis viruses C (HCV), autoimmune hepatic disorders, or sclerosing cholangitis.
• History of concurrent or previously treated non-breast malignancies except for appropriately treated 1) non-melanoma skin cancer and/or 2) in situ carcinomas, including cervix and colon. A patient with previous invasive non-breast cancer is eligible provided he/she has been disease free for more than 5 years.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or Kadcyla 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.

Sponsors & Collaborators

• Spanish Breast Cancer Research Group: lead
• Roche Farma, S.A: collaborator

Study Sites (10)

Hospital Universitario Virgen Macarena

Seville, Andalusia, 41009, Spain

Location

Hospital del Mar

Barcelona, Catalonia, 08003, Spain

Location

Hospital Clínico Universitario "Virgen de la Arrixaca"

El Palmar, Murcia, 30120, Spain

Location

Hospital Universitario Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

ICO L´Hospitalet

Barcelona, 08908, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hopsital Clínico San Carlos

Madrid, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Spain

Location

Biospecimen

Retention: SAMPLES WITH DNA

Primary tumor and/or the recurrence/metastatic prior to receive Kadcyla. Sequential tumor biopsy after 5 days treatment. Metastatic tumor at disease progression. Correlative blood samples will be collected for biomarkers analysis at the following extraction times: Baseline (prior to receive Kadcyla), Cycle 2 (pre-dose), Cycle 4 (pre-dose), every 3 cycles (pre-dose) until disease progression and at the end of treatment.

Study Officials

• Study director

  Hospital del Mar, Barcelona, Spain

  STUDY DIRECTOR

• Study director

  Fundación Jiménez-Díaz, Madrid, Spain

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2019
• First Posted: February 4, 2019
• Study Start: June 12, 2018
• Primary Completion: June 21, 2022
• Study Completion: June 21, 2022
• Last Updated: January 13, 2023

Record last verified: 2023-01

Locations

ES (10)