Study of Trastuzumab-emtansine in Patients With HER2-positive Metastatic Colorectal Cancer Progressing After Trastuzumab and Lapatinib.

NCT03418558 | Unknown Phase 2

• 1 other identifier: 011-IRCC-10IIS-15
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 3

Brief Summary

This is a phase II, open label, multicenter study. Patients with advanced colon rectal cancer (CRC) harboring an amplified HER2 that have been previously treated and progressed with an aNti-HER2 treatment, will be treated with the anti HER2 antibody conjugate trastuzumab emtansine (TDM1). Patients will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death. Main objective of the study is the evaluation of objective response rate according to RECIST 1.1 criteria. Disease control rate, defined as the sum of complete, partial and stable disease patients over total patient, followed by response duration, time to progression and safety are secondary endpoints.

Conditions

Metastatic Colorectal Cancer

Keywords

HER2 AMPLIFICATION

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate according to RECIST 1.1 criteria

  every 9 weeks from date of enrollment until the date of first documented progression or date of death for any cause, whichever came first, assessed up to 48 months

Secondary Outcomes (2)

• Description of the frequency and severity of Adverse Events based on the NCI -CTCAE V4.0

  every 21 days from date of enrollment until the date of first documented progression or date of death for any cause, whichever came first, assessed up to 48 months

• Progression Free Survival

  every 9 weeks from date of enrollment until the date of first documented progression or date of death for any cause, whichever came first, assessed up to 48 months

Study Arms (1)

HERACLES RESCUE

EXPERIMENTAL

Patients will receive trastuzumab-emtansine, iv 3,6 mg/kg every 21 days. Patients will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever come first

Drug: Trastuzumab emtansine

Interventions

Trastuzumab emtansine DRUG

HERACLES RESCUE

Eligibility Criteria

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

You may qualify if:

• Histological/confirmed adenocarcinoma of the colon or rectum with metastatic disease not amenable to salvage surgery.
• Progression (PD) during or after therapy with anti-HER2 therapy including those in HERACLES trial cohort A (trastuzumab and lapatinib) within the HERACLES - A trial.
• ECOG PS \< 2
• Measurable disease as defined by RECIST 1.1 criteria
• Adequate hematological function as defined by: ANC \>= 1.5 x 10\^9/L, platelet count \>=100 x 10\^9/L, hemoglobin \>= 10 g/dL.
• Adequate renal function, as defined by: creatinine \>= 1.5 x UNL
• Adequate hepatobiliary function, as defined by the following baseline liver function tests:
• total serum bilirubin \>=1.5 upper normal limit (UNL) (unless documented Gilbert's syndrome )
• alanine aminotransferase (ALT), aspartate aminotransferase (AST) \>= 2.5xUNL
• alkaline phosphatase (AP) \>= 2.5xUNL; if total alkaline phosphatase (AP) \> 2.5xUNL, alkaline phosphatase liver fraction must be \>= 2.5xUNL
• Adequate contraception for all fertile patients
• Negative pregnancy test.

You may not qualify if:

• Symptomatic brain metastases
• Active infection
• Interval from last anti HER2 therapy \< 2 weeks. Patients in treatment with T-DM1 (provided by third-parties) may be eligible for immediate treatment if not in progression at the time of protocol entry.
• Prior chemotherapy \<4 weeks.
• Impaired cardiac function including any of the following: uncontrolled hypertension (systolic \>150 mmHg and/or diastolic \> 100 mmHg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to first study medication; unstable angina; chronic heart failure (CHF) of New York Heart Association (NYHA) Grade II or higher; or serious cardiac arrhythmia requiring medication, baseline Left Ventricular Ejection Fraction (LVEF) ≤ 55% measured by echocardiography (ECHO)
• Major surgery in the two weeks prior to entering the clinical trial
• Concurrent treatment with any other anti-cancer therapy
• Patient unable to comply with the study protocol owing to psychological, social or geographical reasons
• Pregnant and lactating women
• Men and women of childbearing potential who are not using an effective method of contraception
• Participation in another clinical trial
• Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).

Sponsors & Collaborators

• Fondazione del Piemonte per l'Oncologia: lead

Study Sites (3)

Fondazione del Piemonte per l'Oncologia

Candiolo, 10060, Italy

COMPLETED

Grande Ospedale Metropolitano Niguarda

Milan, Italy

RECRUITING

IOV - Istituto Oncologico Veneto

Padua, Italy

COMPLETED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2018
• First Posted: February 1, 2018
• Study Start: July 8, 2015
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: October 31, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3)