Comparing HAI-90Y (SIR-spheres)+Chemotx LV5FU2 Versus Chemotx LV5FU2 Alone to Treat Colorectal Cancer

NCT ID: NCT01895257

Last Updated: 2017-07-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 162 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2018-12-31

Brief Summary

The investigators propose to conduct a randomised phase III trial evaluating a maintenance strategy comparing hepatic arterial injection of Yttrium-90 resin microspheres plus continuing simplified chemotherapy with/without targeted therapy versus continuing simplified chemotherapy with/without targeted therapy alone for patient with dominant or exclusive and unresectable liver mCRC controlled after 3-6 months of chemotherapy induction.

Detailed Description

The aim of the study is to investigate whether an intensified maintenance treatment of SIRT + simplified maintenance chemotherapy has a benefit in terms of time to progression (TTP) compared to simplified chemotherapy maintenance alone, in patients with stable disease after 3-6 months induction therapy. We would like to demonstrate the feasibility and safety of this approach and to investigate if this strategy has the potential to increase the outcome of the patient.

Primary end-point:

• Time to first progression (TTP1 overall)

Secondary end-points:

• Time to global progression (TTP1 + TTP2), Time to second progression (TTP2), TTP1 liver only
• Progression Free Survival (PFS)
• Overall Survival (OS)
• Safety
• Ro resection rate
• Quality of Life

Exploratory analysis:

• Prediction and evaluation of SIR-spheres treatment response (only for Belgian centres)

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A: systemic chemotherapy LV5FU2 alone

Modified LV5FU2 as described in protocol (6.2.1) D1-2 +/- bevacizumab or cetuximab or panitumumab (according its previous use) every 2 weeks

Group Type: ACTIVE_COMPARATOR

systemic chemotherapy LV5FU2

Intervention Type: DRUG

Systemic chemotherapy with modified LV5FU2 will be administered according to the following regimen.

Cycle 1 onwards:

Day 1 Hour 0: Leucovorin L (levoleucovorin) 200 mg/m2 (or folinic acid 400 mg/m²) in 250 ml glucose 5%, 2-hour IV infusion Hour + 2: 5-FU bolus 400 mg/m2, IV bolus Hour + 2: 5-FU continuous infusion 2400 mg/m2, 46-hour cont. IV infusion Day 14 End of cycle. To be repeated every 14 days until evidence of treatment failure.

B:SIR-spheres+systemic chemotherapy LV5FU2

ARM B: (Hepatic Arterial Infusion) HAI-90Y radioembolization (SIR-spheres injection) + modified LV5FU2 +/- bevacizumab or cetuximab or panitumumab according its previous use (refer to protocol).

Group Type: ACTIVE_COMPARATOR

HAI-90Y radioembolization (SIR-spheres injection)

Intervention Type: DEVICE

Patients randomised to receive the combination of SIR-Spheres microspheres plus systemic chemotherapy LV5FU2 need to be assessed in order to determine their suitability for SIRT.

1. Hepatic Angiogram

2. Liver-Lung Break-Through Nuclear Scan

Interventions

HAI-90Y radioembolization (SIR-spheres injection)

Patients randomised to receive the combination of SIR-Spheres microspheres plus systemic chemotherapy LV5FU2 need to be assessed in order to determine their suitability for SIRT.

1. Hepatic Angiogram

2. Liver-Lung Break-Through Nuclear Scan

Intervention Type: DEVICE

systemic chemotherapy LV5FU2

Systemic chemotherapy with modified LV5FU2 will be administered according to the following regimen.

Cycle 1 onwards:

Day 1 Hour 0: Leucovorin L (levoleucovorin) 200 mg/m2 (or folinic acid 400 mg/m²) in 250 ml glucose 5%, 2-hour IV infusion Hour + 2: 5-FU bolus 400 mg/m2, IV bolus Hour + 2: 5-FU continuous infusion 2400 mg/m2, 46-hour cont. IV infusion Day 14 End of cycle. To be repeated every 14 days until evidence of treatment failure.

Intervention Type: DRUG

Other Intervention Names

Sir-spheres microspheres; SIRT; Leucovorin L; Levoleucovorin; 5-FU; 5-Fluoro-Uracil

Eligibility Criteria

Inclusion Criteria

1. Willing and able to provide written informed consent

2. Histologically confirmed adenocarcinoma of the colon or rectum, with or without primary tumour in situ. Unequivocal and measurable (RECIST 1.1) CT evidence of liver metastases which are not treatable by surgical resection and/or local ablation with curative intent at the time of trial entry.

3. Partial response or stable disease (RECIST 1.1 criteria, controlled metastatic disease) after chemotherapy induction with oxaliplatin and/or irinotecan based induction chemotherapy (doublet or triplet combinations) +/- targeted therapies during 3 to 6 months.

4. Trial inclusion must be performed between 3 and 6 months since the date of the first course of chemotherapy (induction) administration.

5. Limited extra-hepatic metastases in the lung and/or lymph nodes are permitted. Metastases in the lung must either be not more than five nodules in number with no individual nodule more than 1 cm in diameter or 1 single lesion of up to 1.7 cm in diameter. Involvement of lymph nodes in 1 single anatomic region (pelvis, abdomen or chest) are permitted provided their longest diameter measures less than 2 cm.

6. All imaging evidence used as part of the screening process must be within 28 days prior to the time of randomisation.

7. Suitable for either treatment regimen as determined by clinical assessment undertaken by the Investigator.

8. Patients may have received adjuvant chemotherapy or (neo-) adjuvant chemo-radiotherapy to the pelvis, provided the last dose of chemotherapy was administered at least 6 months prior to begin chemotherapy induction. Previous radiotherapy to the pelvis is not an exclusion criterion.

9. WHO performance status 0 - 1

10. Adequate hematological, renal and hepatic function as follows:

Hematological Neutrophils > 1.5 x 109/L Platelets > 100 x 109/L Renal Creatinine < 1.5 x ULN (Upper Limit Normal) Hepatic Bilirubin ≤ 1.0 X ULN Albumin ≥ 30g/L ALT ≤ 5.0 x ULN AST ≤ 5.0 x ULN LDH ≤ 2.5 x ULN The date of blood tests must be within 28 days prior to the time of randomisation.

11. Age 18 years or older.

12. Female patients must either be postmenopausal, sterile (surgically or radiation- or chemically-induced), or if sexually active using an acceptable method of contraception.

13. Male patients must be surgically sterile or if sexually active and having a pre-menopausal partner must be using an acceptable method of contraception.

14. Life expectancy of at least 3 months without any active treatment.

Exclusion Criteria

1. Evidence of ascites, cirrhosis, portal hypertension, main portal venous tumour involvement or thrombosis as determined by clinical or radiological assessment.

2. More than 6 months since last chemotherapy administration before trial inclusion.

3. Previous radiotherapy delivered to the upper abdomen.

4. Non-malignant disease that would render the patient unsuitable for treatment according to this protocol.

5. Prior major liver resection: remnant liver < 50% of the initial liver volume. Patient with a biliary stent can be included.

6. Liver tumor involvement > 80% before study inclusion (not at diagnosis but when trial inclusion for the patient is planned).

7. Resectable metastatic disease at trial inclusion.

8. Progressive disease during first-line metastatic chemotherapy. Adjuvant chemotherapy for colorectal cancer is not an exclusion criterion provided that it was completed more than 6 months prior to start of 1st line chemotherapy.

9. No oxaliplatin or irinotecan use during the first 3 to 6 months induction chemotherapy.

10. Pregnant or breast feeding.

11. Concurrent or prior history of cancer other than adequately treated non melanoma skin cancer or carcinoma in situ of the cervix.

12. Severe allergy to non-ionic contrast agents which would prevent contrast media use during the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universiteit Antwerpen

OTHER

Sponsor Role: lead

Responsible Party

Prof. Marc Peeters

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marc Peeters

Role: STUDY_CHAIR

Universiteit Antwerpen

Marc Van den Eynde

Role: STUDY_CHAIR

University of St-Luc

Locations

University of Antwerp

Edegem, Antwerp, Belgium

Site Status: RECRUITING

ASZ Aalst

Aalst, , Belgium

Site Status: ACTIVE_NOT_RECRUITING

Institut Jules Bordet

Brussels, , Belgium

Site Status: ACTIVE_NOT_RECRUITING

CUB Hôpital Erasme

Brussels, , Belgium

Site Status: ACTIVE_NOT_RECRUITING

University of St-Luc

Brussels, , Belgium

Site Status: RECRUITING

Grand Hôpital de Charleroi

Charleroi, , Belgium

Site Status: RECRUITING

ZOL Genk

Genk, , Belgium

Site Status: RECRUITING

AZ St-Lucas Gent

Ghent, , Belgium

Site Status: NOT_YET_RECRUITING

AZ Groeninge

Kortrijk, , Belgium

Site Status: RECRUITING

CHU de Liège

Liège, , Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Micheline Stempin

Role: CONTACT

clinicaltrials@bgdo.org

+32474074584

Peggy De Clercq

Role: CONTACT

peggy.declercq@uza.be

+32(0)8215307

Facility Contacts

Jaarke Vannoote, MD

Role: primary

Monique Troch, MD

Role: primary

Philippe Vergauwe, MD

Role: primary

Other Identifiers

2012-000508-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

The SIR-step trial

Identifier Type: -

Identifier Source: org_study_id