Metastatic colorectal carcinoma (mCRC) MedDRA version: 14.1 Level: HLT Classification code 10010023 Term: Colorectal neoplasms malignant System Organ Class: 100000004864
Conditions
Interventions
Trade Name: HERCEPTIN*EV 1FL 150MG
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: TRASTUZUMAB
CAS Number: 180288-69-1
Concentration unit: mg/kg milligram(s)/kilogram
C
Sponsors
FONDAZIONE DEL PIEMONTE PER L'ONCOLOGIA IRCC DI CANDIOLO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all the following inclusion criteria to be eligible for enrolment into the study: 1. Histological/confirmed adenocarcinoma of the colon or rectum with metastatic disease not amenable to salvage surgery 2. Pathology mandatory requirements: a. the original tumour specimen must be KRAS WT and HER2 IHC 3+ positive, with = 50% positive cells. This criterium is pending confirmation from the ongoing HERACLES DGX validation study. b. the original paraffin block or a minimum of 15 polarized unstained slides from the original paraffin block must be made available to the Pathology Core within 15 days from registration. 3. Age =18 4. ECOG PS 0-1 5. Measurable disease as defined by RECIST 1.1 criteria 6. Progression (PD) while on treatment, or within 6 months from therapy with approved standard drugs 7. Unless otherwise contraindicated patients should have received and failed the following previous therapies for mCRC: fluoropirimidines, oxaliplatin, irinotecan, cetuximab or panitumumab containing regimens. Bevacizumab is allowed 8. Adequate haematological function as defined by: ANC ? 1.5 x 109/L, platelet count ?100 x 109/L, haemoglobin ? 10 g/dL. 9. Adequate renal function, as defined by: creatinine ? 1.5 x UNL 10. Adequate hepatobiliary function, as defined by the following baseline liver function tests: o total serum bilirubin ?1.5 upper normal limit (UNL) o alanine aminotransferase (ALT), aspartate aminotransferase (AST) ? 2.5xUNL o alkaline phosphatase (AP) ? 2.5xUNL; if total alkaline phosphatase (AP) > 2.5xUNL, alkaline phosphatase liver fraction must be ? 2.5xUNL 11. Adequate contraception for all fertile patients 12. Negative pregnancy test. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 14
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Radiotherapy = 4 weeks prior to enrolment 2. Other chemotherapy or biological therapy treatment = 4 weeks prior to enrolment 3. Symptomatic brain metastases 4. Active infection 5. Gastro-intestinal abnormalities, inability to take oral medication, any condition affecting absorption 6. Impaired cardiac function including any of the following: uncontrolled hypertension (systolic >150 mmHg and/or diastolic > 100 mmHg) or clinically significant (ie 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) 7. Major surgery in the two weeks prior to entering the clinical trial 8. Concurrent treatment with any other anti-cancer therapy 9. History of another neoplastic disease (except basal cell carcinoma of the skin or uterine cervix carcinoma in situ adequately treated), unless in remission for = 5 years 10. Patient unable to comply with the study protocol owing to psychological, social or geographical reasons 11. Pregnant and lactating women 12. Patients with history of hypersensitivity to either IMPs or excipients 13. Men and women of childbearing potential who are not using an effective method of contraception 14. Participation in another clinical trial or treatment with any investigational product within 4 weeks prior to inclusion in this study. 15. 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Define the antitumor activity of the anti-HER2 combinations of lapatinib + trastuzumab and pertuzumab + trastuzumab given to two separate, sequential cohorts of patients with chemo-refractory advanced disease and HER2 amplified tumours.;Secondary Objective: 1. Define the safety profile of the two combinations 2. Define the Progression Free Survival (PFS);Primary end point(s): Objective Response Rate according to RECIST 1.1 criteria;Timepoint(s) of evaluation of this end point: Tumor response will be assessed starting on week 8 and every 8 weeks thereafter. Tumor response MUST be confirmed 4 + 1week from first assessment of response. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Description of the frequency and severity of Adverse Events based on the NCI –CTCAE V4.0 2. PFS 3. Correlation between selected tumor biomarkers evaluated in tumor specimens (including but not limited to mutations of effectors downstream of HER-family receptors - such as KRAS, BRAF, and PIK3CA, or related tyrosine kinase receptors), and tumor response/resistance to experimental treatment 2. Comparison of tumor biomarkers status in blood samples collected before start of treatment, with that collected during treatment and after progression;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Countries
Italy
Contacts
Public Contactdirezione scientifica
SENDO Tech
Outcome results
None listed