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

• Register: EUCTR
• Last refreshed on: 25 May 2021
• Main ID: EUCTR2014-001017-61-SK
• Date of registration: 10/11/2014
• Prospective Registration: Yes
• Primary sponsor: 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: 10/12/2014
• Target sample size: 1400
• 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: 6
• 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:
All Cohorts:
- 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
Disease-related:
- Histologically confirmed CRC with metastatic CRC confirmed radiologically
- 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 740
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 660

Exclusion criteria:
All Cohorts:
-Less than 6 months from completion of any prior neoadjuvant or adjuvant chemotherapy,radiotherapy or surgery
-Prior or current treatment with bevacizumab or any other antiangiogenic drug
-Current or recent (within 10 days of enrollment) use of aspirin (> 325 mg/day), clopidogrel (> 75mg/day), therapeutic oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes (prophylactic uses allowed)
-Active infection requiring intravenous antibiotics at the start of 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 patient has been disease-free for 5 years prior to study entry
-Inadequately controlled hypertension; prior history of (H/o) hypertensive crisis or hypertensive encephalopathy
-Clinically significant (CS) (i.e. active) cardiovascular disease (eg., cerebrovascular accidents and/or myocardial infarction -Significant vascular disease within 6 months of start of induction treatment
-Active symptomatic or untreated CNS metastases; CNS disease other than supratentorial or cerebellar metastases (i.e. patients with metastases to midbrain, pons, medulla or spinal cord are excluded); H/o or known carcinomatous meningitis. Patients requiring anticonvulsants or corticosteroids for symptom control. Patients without measureable disease outside the CNS are excluded from study.
-Known hypersensitivity to any component of any of the study induction or maintenance treatment medications
-Pregnancy or lactation
-Inability to swallow medications and have malabsorption syndrome
Cohort 1:
-Refractory nausea and vomiting, malabsorption, external biliary shunt or significant bowel resection that would preclude adequate absorption
-H/o or presence of CS ventricular or atrial dysrhythmias
-Corrected QT interval >/= 450 msec as assessed within 3 weeks prior to randomization, long QT syndrome, uncorrectable electrolyte abnormalities or requirement for medicinal products known to prolong the QT interval
-ECOG PS > 2 (ECOG PS=2 and Low BMI at investigators judgement)
Cohort 2 :
-Prior allogeneic bone marrow or prior solid organ transplantation
-H/o of idiopathic pulmonary fibrosis, drug induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on most recent chest imaging
-Active tuberculosis
-Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
-Severe infection within 4 weeks prior to start of maintenance treatment
-Treatment with systemic corticosteroids or other systemic immunosuppressive medications
-If receiving a RANKL inhibitor, unwilling to adopt alternative treatment
Cohort 3:
-Current dyspnoea at rest
-Insulin-dependent diabetes
-Requirement for concurrent use of the antiviral agent sorivudine or chemically related analogues
-Known hypersensitivity to murine proteins
-Left ventricular ejection fraction < 50% after completion of induction treatment
-CS cardiovascular disease; H/o or active congestive heart failure and serious cardiac arrhythmia requiring treatment
Cohort 4:
-Known hypersensitivity or allergy to Chine

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

Health Condition(s) or Problem(s) studied

METASTATIC COLORECTAL CANCER
MedDRA version: 20.0 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: Atezolizumab
Product Code: RO5541267/F03
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Atezolizumab
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-

Product Name: Cobimetinib (GDC-0973)
Product Code: RO5514041/F04
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Cobimetinib (GDC-0973)
CAS Number: 934660-93-2
Current Sponsor code: RO5514041/F04
Other descriptive name: COBIMETINIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Product Name: Cobimetinib (GDC-0973)
Product Code: RO5514041/F09
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Cobimetinib (GDC-0973)
CAS

Primary Outcome(s)

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

Primary end point(s): 1. Progression-free survival (PFS) is defined as the time from randomisation into the Maintenance Treatment Phase until disease progression per Investigator assessment using RECIST 1.1 or death from any cause, whichever occurs first

Main Objective: • To evaluate progression-free survival (PFS)

Timepoint(s) of evaluation of this end point: 1. From randomization until disease progression or death from any cause

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 up to 30 days after last dose of study treatment
7. From baseline until end of study (up to 24 months follow-up of the last patient)

Secondary ID(s)

MO29112

2014-001017-61-IT

NCT02291289

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 09/12/2014
Contact:

Results

• Results available: Yes
• Date Posted: 12/06/2020
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001017-61/results