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

• Status: Unknown status
• Trial end date: 2019-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fondazione del Piemonte per l'Oncologia
• Treatments: Ado-Trastuzumab Emtansine; Lapatinib; Maytansine; Trastuzumab

Criteria

Inclusion Criteria:

1. Histological/confirmed adenocarcinoma of the colon or rectum with metastatic disease not amenable to salvage surgery.

2. 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.

3. ECOG PS < 2

4. Measurable disease as defined by RECIST 1.1 criteria

5. Adequate hematological function as defined by: ANC >= 1.5 x 10^9/L, platelet count >=100 x 10^9/L, hemoglobin >= 10 g/dL.

6. Adequate renal function, as defined by: creatinine >= 1.5 x UNL

7. Adequate hepatobiliary function, as defined by the following baseline liver function tests:

1. total serum bilirubin >=1.5 upper normal limit (UNL) (unless documented Gilbert's syndrome )

2. alanine aminotransferase (ALT), aspartate aminotransferase (AST) >= 2.5xUNL

3. alkaline phosphatase (AP) >= 2.5xUNL; if total alkaline phosphatase (AP) > 2.5xUNL, alkaline phosphatase liver fraction must be >= 2.5xUNL

8. Adequate contraception for all fertile patients

9. Negative pregnancy test.

Exclusion Criteria:

1. Symptomatic brain metastases

2. Active infection

3. 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.

4. Prior chemotherapy <4 weeks.

5. 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)

6. Major surgery in the two weeks prior to entering the clinical trial

7. Concurrent treatment with any other anti-cancer therapy

8. Patient unable to comply with the study protocol owing to psychological, social or geographical reasons

9. Pregnant and lactating women

10. Men and women of childbearing potential who are not using an effective method of contraception

11. Participation in another clinical trial

12. 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).