A clinical trial evaluating tumour marker-driven treatment choices for advanced colorectal cancer.

• Register: EUCTR
• Last refreshed on: 20 August 2018
• Main ID: EUCTR2014-001017-61-ES
• Date of registration: 29/10/2015
• Prospective Registration: Yes
• Primary sponsor: Roche Farma S.A. en nombre de F. Hoffmann-La Roche Ltd
• Public title: A clinical trial evaluating tumour marker-driven treatment choices for advanced colorectal cancer.
• Scientific title: A MULTI-CENTRE RANDOMISED CLINICAL TRIAL OF BIOMARKER-DRIVEN MAINTENANCE TREATMENT FOR FIRST-LINE METASTATIC COLORECTAL CANCER (MODUL) - MODUL
• Date of first enrolment: 23/12/2015
• Target sample size: 1442
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001017-61
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Algeria, Argentina, Austria, Belgium, Brazil, China, Denmark, Egypt, France, Germany, Greece, Italy, Macedonia, the former Yugoslav Republic of, Mexico, Netherlands, Poland, Portugal, Russian Federation, Serbia, Slovakia, Slovenia, Spain, Sweden, Turkey, United Kingdom

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
Función hematológica- Male and female patients >/= 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status of - At least 16 weeks of life expectancy at time of entry into the study
- Histologically confirmed metastatic colorectal cancer (CRC)
- Measureable, unresectable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1
- No prior chemotherapy for CRC in the metastatic setting
- Archival tumor formalin-fixed paraffin-embedded tissue block from the primary tumor obtained at the time of the initial diagnosis is available
- Adequate hematological, liver and renal function
- Agreement to use highly effective measures of contraception
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 721
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 721

Exclusion criteria:
? Less than six months from completion of any prior adjuvant chemotherapy, radiotherapy or surgery
? Prior or current treatment with bevacizumab or any other anti-angiogenic drug (i.e. VEGF or vascular endothelial growth factor receptor [VEGFR] therapies or tyrosine kinase inhibitors)
? Current or recent (within 10 days of study enrollment) use of aspirin (> 325 mg/day), clopidogrel (> 75 mg/day), or current or recent (within 10 days prior to the start of study induction treatment) use of therapeutic oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes (prophylactic uses allowed)
? Active infection requiring intravenous antibiotics at the start of study induction treatment
? Previous or concurrent malignancy, except for adequately treated basal or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for five years prior to study entry
? Inadequately controlled hypertension; prior history of hypertensive crisis or hypertensive encephalopathy
? Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents ? Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of start of study induction treatment
? Active or untreated CNS metastases; treatment of brain metastases, either by surgical or radiation techniques, must have been completed > 4 weeks prior to start of study induction treatment
? Known hypersensitivity to any component of bevacizumab or any of the study medications
? Pregnancy or lactation
? Archival primary tumor sample provided found not to include an adequate quantity of tumor tissue with sufficient quality to conduct biomarker testing

Cohort 1 BRAF(mut) Exclusion Criteria
? Inability to swallow pills
? Refractory nausea and vomiting, malabsorption, external biliary shunt or significant bowel resection that would preclude adequate absorption
? History or presence of clinically significant ventricular or atrial dysrhythmias
? Corrected QT (QTc) interval >/= 480 msec at baseline or history of congenital long QT syndrome or uncorrectable electrolyte abnormalities

Cohort 2 No Biomarker Exclusion Criteria
? History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener?s granulomatosis, Sjögren?s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
? Prior allogeneic bone marrow transplantation or prior solid organ transplantation
? History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis at Screening
? Positive test for human immunodeficiency virus (HIV)
? Active hepatitis B or hepatitis C at Screening
? Active tuberculosis
? Administration of a live, attenuated vaccine within four weeks prior to start of maintenance treatment or anticipation that such a live attenuated vac

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

METASTATIC COLORECTAL CANCER
MedDRA version: 18.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Avastin
Product Name: Bevacizumab
Product Code: RO4876646/F02
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BEVACIZUMAB
CAS Number: 216974-75-3
Current Sponsor code: RO4876646
Other descriptive name: rhuMAb VEGF, anti-VEGF
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Product Name: MPDL3280A
Product Code: RO5541267/F03
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: n.a.
CAS Number: n.a.
Current Sponsor code: RO5541267
Other descriptive name: MPDL3280A; Anti-PDL1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-

Trade Name: Zelboraf 240 mg Film-coated Tablets
Product Code: RO5185426/F17
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Vemurafenib
CAS Number: 918504-65-1
Current Sponsor code: RO5185426
Other descriptive name: VEMURAFENIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 240-

Trade Name: Erbitux®
Product Code: Ro 546-9926
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: CETUXIMAB
CAS Number: 205923-56-4
Current Sponsor code: RO5469926
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Primary end point(s): 1) Proportion of patients with a 20% reduction in tumor size in the Maintenance Treatment Phase after 2 months of treatment
2) Progression-free survival (PFS)

Timepoint(s) of evaluation of this end point: 1) After two months of maintenance therapy
2) From randomization until disease progression ordeath from any cause

Main Objective: ? Assessing early efficacy during the Maintenance Treatment Phase based on a 20% reduction in tumour size after 2 months of treatment
? Evaluating PFS

Secondary Objective: ? OS
? ORR
? Disease control rate (DCR)
? Time to treatment response (TTR)
? Duration of response (DoR)
? ECOG performance status
? Incidence, nature and severity of adverse events (AEs)

Secondary Outcome(s)

Secondary end point(s): 1) Overall survival
2) Overall response rate, calculated as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) determined according to RECIST 1.1
3) Disease control rate (DCR), calculated as the proportion of patients with a best overall response of CR, PR or stable disesase (SD) as determined according to RECIST 1.1
4) Time to treatment response (TTR), calculated as the time from randomization to the first occurrence of a documented objective response (CR or PR) determined according to RECIST 1.1
5) Duration of response (DoR), , defined as the time from the first assessment of CR or PR until disease progression or death from any cause, whichever occurs first
6) Change in ECOG performance status
7) Incidence of adverse events (AEs)

Timepoint(s) of evaluation of this end point: 1) From randomization until death from any cause
2) From randomization until disease progression
3) From randomization until disease progression
4) From randomization until disease progression or death from any cause
5) From randomization until disease progression or death from any cause
6) From baseline until end of study (up to 6 years)
7) From baseline until end of study (up to 6 years)

Secondary ID(s)

2014-001017-61-IT

MO29112

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd