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

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ClinicalTrials.gov Identifier: NCT01895257
Recruitment Status : Recruiting
First Posted : July 10, 2013
Last Update Posted : July 7, 2017
Sponsor:
Information provided by (Responsible Party):
Prof. Marc Peeters, Universiteit Antwerpen

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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Device: HAI-90Y radioembolization (SIR-spheres injection) Drug: systemic chemotherapy LV5FU2 Phase 3

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)


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 162 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomised Phase III Trial Comparing Hepatic Arterial Injection of Yttrium-90 Resin Microspheres (SIR-spheres) Plus Systemic Maintenance Therapy Versus Systemic Maintenance Therapy Alone for Patients With Unresectable Liver Metastases From Colorectal Cancer Which Are Controlled After Induction Systemic Therapy
Study Start Date : August 2013
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 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
Drug: 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.

Other Names:
  • Leucovorin L
  • Levoleucovorin
  • 5-FU
  • 5-Fluoro-Uracil

Active Comparator: 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).
Device: 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
Other Names:
  • Sir-spheres microspheres
  • SIRT




Primary Outcome Measures :
  1. Time to progression (TTP1 overall) [ Time Frame: Up to 36 months ]
    Time to first progression (TTP1 overall)


Secondary Outcome Measures :
  1. Time to global progression (TTP1 + TTP2) [ Time Frame: Up to 42 months ]
    - Time to global progression (TTP1 + TTP2), Time to second progression (TTP2), TTP1 liver only

  2. PFS [ Time Frame: Up to 42 months ]
    Progression free survival

  3. Safety [ Time Frame: Up to 42 months ]
  4. R0 resection rate [ Time Frame: Up to 42 months ]
  5. Quality of life [ Time Frame: Up to 42 months ]

    Using

    • EORTC QLQ C30
    • EQ-5D

  6. Overall Survival (OS) [ Time Frame: Up to 42 months ]

Other Outcome Measures:
  1. SIR-spheres treatment [ Time Frame: Up to 42 months ]
    Prediction and evaluation of SIRspheres treatment response (only for Belgian sites)



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01895257


Contacts
Contact: Micheline Stempin +32474074584 clinicaltrials@bgdo.org
Contact: Peggy De Clercq +32(0)8215307 peggy.declercq@uza.be

Locations
Belgium
University of Antwerp Recruiting
Edegem, Antwerp, Belgium, 2650
Principal Investigator: Marc Peeters, MD, PhD         
ASZ Aalst Active, not recruiting
Aalst, Belgium, 9300
Institut Jules Bordet Active, not recruiting
Brussels, Belgium, 1000
CUB Hôpital Erasme Active, not recruiting
Brussels, Belgium, 1070
University of St-Luc Recruiting
Brussels, Belgium, 1200
Principal Investigator: Marc Van den Eynde         
Grand Hôpital de Charleroi Recruiting
Charleroi, Belgium, 6000
Principal Investigator: Javier Carrasco, MD         
ZOL Genk Recruiting
Genk, Belgium, 3600
Contact: Jaarke Vannoote, MD         
AZ St-Lucas Gent Not yet recruiting
Gent, Belgium, 9000
Contact: Monique Troch, MD         
AZ Groeninge Recruiting
Kortrijk, Belgium, 8500
Contact: Philippe Vergauwe, MD         
CHU de Liège Recruiting
Liège, Belgium, 4000
Principal Investigator: Marc Polus, MD         
Sponsors and Collaborators
Universiteit Antwerpen
Investigators
Study Chair: Marc Peeters Universiteit Antwerpen
Study Chair: Marc Van den Eynde University of St-Luc

Responsible Party: Prof. Marc Peeters, Professor, Universiteit Antwerpen
ClinicalTrials.gov Identifier: NCT01895257     History of Changes
Other Study ID Numbers: The SIR-step trial
2012-000508-14 ( EudraCT Number )
First Posted: July 10, 2013    Key Record Dates
Last Update Posted: July 7, 2017
Last Verified: July 2017

Keywords provided by Prof. Marc Peeters, Universiteit Antwerpen:
TTP1
TTP2
PFS
Safety
R0 resection rate
Quality of life
Overall Survival

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antidotes
Protective Agents