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

NCT01895257 | Unknown Phase 3 DMC

• 2 other identifiers: The SIR-step trial2012-000508-14
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 10

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.

Conditions

Colorectal Cancer

Keywords

TTP1; TTP2; PFS; Safety; R0 resection rate; Quality of life; Overall Survival

Outcome Measures

Primary Outcomes (1)

• Time to progression (TTP1 overall)

  Time to first progression (TTP1 overall)

  Up to 36 months

Secondary Outcomes (6)

• Time to global progression (TTP1 + TTP2)

  Up to 42 months

• PFS

  Up to 42 months

• Safety

  Up to 42 months

• R0 resection rate

  Up to 42 months

• Quality of life

  Up to 42 months

Other Outcomes (1)

• SIR-spheres treatment

  Up to 42 months

Study Arms (2)

A: systemic chemotherapy LV5FU2 alone

ACTIVE COMPARATOR

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

Drug: systemic chemotherapy LV5FU2

B:SIR-spheres+systemic chemotherapy LV5FU2

ACTIVE COMPARATOR

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).

Device: HAI-90Y radioembolization (SIR-spheres injection)

Interventions

HAI-90Y radioembolization (SIR-spheres injection) 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

Also known as: Sir-spheres microspheres, SIRT

B:SIR-spheres+systemic chemotherapy LV5FU2

systemic chemotherapy LV5FU2 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.

Also known as: Leucovorin L, Levoleucovorin, 5-FU, 5-Fluoro-Uracil

A: systemic chemotherapy LV5FU2 alone

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent
• 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.
• 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.
• 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.
• All imaging evidence used as part of the screening process must be within 28 days prior to the time of randomisation.
• Suitable for either treatment regimen as determined by clinical assessment undertaken by the Investigator.
• WHO performance status 0 - 1
• 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.
• Age 18 years or older.
• Female patients must either be postmenopausal, sterile (surgically or radiation- or chemically-induced), or if sexually active using an acceptable method of contraception.
• Male patients must be surgically sterile or if sexually active and having a pre-menopausal partner must be using an acceptable method of contraception.
• Life expectancy of at least 3 months without any active treatment.

You may not qualify if:

• Evidence of ascites, cirrhosis, portal hypertension, main portal venous tumour involvement or thrombosis as determined by clinical or radiological assessment.
• Previous radiotherapy delivered to the upper abdomen.
• Non-malignant disease that would render the patient unsuitable for treatment according to this protocol.
• Prior major liver resection: remnant liver \< 50% of the initial liver volume. Patient with a biliary stent can be included.
• No oxaliplatin or irinotecan use during the first 3 to 6 months induction chemotherapy.
• Pregnant or breast feeding.
• Concurrent or prior history of cancer other than adequately treated non melanoma skin cancer or carcinoma in situ of the cervix.
• Severe allergy to non-ionic contrast agents which would prevent contrast media use during the study.

Sponsors & Collaborators

• Universiteit Antwerpen: lead

Study Sites (10)

University of Antwerp

Edegem, Antwerp, 2650, Belgium

RECRUITING

ASZ Aalst

Aalst, 9300, Belgium

ACTIVE NOT RECRUITING

Institut Jules Bordet

Brussels, 1000, Belgium

ACTIVE NOT RECRUITING

CUB Hôpital Erasme

Brussels, 1070, Belgium

ACTIVE NOT RECRUITING

University of St-Luc

Brussels, 1200, Belgium

RECRUITING

Grand Hôpital de Charleroi

Charleroi, 6000, Belgium

RECRUITING

ZOL Genk

Genk, 3600, Belgium

RECRUITING

AZ St-Lucas Gent

Ghent, 9000, Belgium

NOT YET RECRUITING

AZ Groeninge

Kortrijk, 8500, Belgium

RECRUITING

CHU de Liège

Liège, 4000, Belgium

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Levoleucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Leucovorin; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Marc Peeters

  Universiteit Antwerpen

  STUDY CHAIR

• Marc Van den Eynde

  University of St-Luc

  STUDY CHAIR

Central Study Contacts

Micheline Stempin

CONTACT

+32474074584; clinicaltrials@bgdo.org

Peggy De Clercq

CONTACT

+32(0)8215307; peggy.declercq@uza.be

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 6, 2013
• First Posted: July 10, 2013
• Study Start: August 1, 2013
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2018
• Last Updated: July 7, 2017

Record last verified: 2017-07

Locations

BE (10)