Clinical trial NCT01910610: Multi-Line Therapy Trial in Unresectable Metastatic Colorectal Cancer
Official title: Multi-Line Therapy Trial in Unresectable Wild-Type RAS Metastatic Colorectal Cancer. A GERCOR Randomized Open-label Phase III Study.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Colorectal Cancer Metastatic
Keywords: wild-type RAS metastatic colorectal cancer
Lead sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2013-07-29
Enrollment: 464
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: STRATEGIC-1 is a study designed to determine the best sequence of therapy in patients with metastatic colorectal cancer.

Detailed description: This is a phase III study assessing 2 mutli-line therapeutic strategies in patients with unresectable wild-type RAS metastatic colorectal cancer. All the available treatments are being used in each strategy (oxaliplatine, irinotecan, fluoropyrimidines, bevacizumab, cetuximab or panitumumab) but in a different order:

STRATEGY A: FOLFIRI-cetuximab, followed by oxaliplatin-based chemotherapy with bevacizumab vs.

STRATEGY B: OPTIMOX-bevacizumab, followed by irinotecan-based chemotherapy with bevacizumab, followed by anti-EGFR mab with or without irinotecan.

Eligibility criteria: Inclusion Criteria:

1. Signed and dated informed consent, and willing and able to comply with protocol requirements,
2. Histologically proven adenocarcinoma of the colon and/or rectum,
3. Wild-type RAS tumor no mutation in exon 2 \[codon 12/13\], exon 3 \[codon 59/61\] and exon 4 \[codon 117/146\] of both KRAS and NRAS genes (local assessment, performed either on primary tumor or metastasis), In exceptional circumstances, RAS mutational status (KRAS and NRAS) can be pending at time of randomization, provided it is obtained within the first two cycles of first line therapy
4. Metastatic disease confirmed,
5. No prior therapy for metastatic disease (in case of previous adjuvant therapy, interval from end of chemotherapy and relapse must be \>6 months for fluoropyrimidine alone or \>12 months for oxaliplatin-based, bevacizumab-based, or cetuximab-based therapy),
6. Duly documented unresectable metastatic disease, ie not suitable for complete carcinological surgical resection at inclusion \[NB: patients with unresectable disease at study entry but with any potential of salvage surgery after induction therapy are eligible\],
7. At least one measurable or evaluable lesion as assessed by CT-scan or MRI (Magnetic Resonance Imaging) according to RECIST v1.1,
8. Age ≥18 years,
9. ECOG Performance status (PS) 0-2,
10. Hematological status: neutrophils (ANC) ≥1.5x109/L; platelets ≥100x109/L; haemoglobin ≥9g/dL,
11. Adequate renal function: serum creatinine level \<150µM,
12. Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alkaline phosphatase \<5xULN,
13. Proteinuria \<2+ (dipstick urinalysis) or ≤1g/24hour,
14. Baseline evaluations performed before randomization when the KRAS WT status is known: clinical and blood evaluations no more than 2 weeks (14 days) prior to randomization, tumor assessment (CT-scan or MRI, evaluation of non-measurable lesions) no more than 3 weeks (21 days) prior to randomization,
15. Female patients must commit to using reliable and appropriate methods of contraception during the trial and until at least six months after the end of study treatment (when applicable). Male patients with a partner of childbearing potential must agree to use contraception in addition to having their partner use another contraceptive method during the trial and until at least 6 months after the end of the study treatment,
16. Registration in a national health care system (CMU included for France).

Exclusion Criteria:

1. History or evidence upon physical examination of CNS metastasis (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy), unless adequately treated,
2. Exclusive bone metastasis,
3. Uncontrolled hypercalcemia,
4. Pre-existing permanent neuropathy (NCI grade ≥2),
5. Uncontrolled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \>100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy,
6. Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
7. Treatment with any investigational medicinal product within 28 days prior to study entry,
8. Other serious and uncontrolled non-malignant disease,
9. Gilbert's syndrome,
10. Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for \>5 years,
11. Major surgery (open biopsy, surgical resection, wound revision or any other major surgery involving entry into body cavity) or significant traumatic injury within the last 28 days prior to randomization, and/or minor surgical procedure including placement of a vascular device within 2 days of first study treatment,
12. Pregnant or breastfeeding women,
13. Patients with known allergy/hypersensitivity to any component of study drugs,
14. History of arterial thrombo and/or embolic event (e.g. myocardial infarction, stroke,...) within 6 months prior to randomization,
15. Chronic inflammatory bowel disease
16. Total bowel obstruction,
17. History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to randomization,
18. Serious, non-healing wound, active ulcer or untreated bone fracture,
19. History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding,
20. Current or recent (within 10 days of randomization) use of aspirin (\>325 mg/d), clopidogrel (\>75 mg/d) or use of oral anticoagulants or thrombolytic agents.
21. Concomitant administration of live, attenuated virus vaccine such as yellow fever vaccine
22. Concomitant administration of prophylactic phenytoin.
23. Treatment with sorivudine or its chemically related analogues, such as brivudine.
24. Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency.
25. Concomitant use with St John's Wort
26. Patients with interstitial pneumonitis or pulmonary fibrosis

Primary outcomes:
measure: Duration of Disease Control (DDC)
timeFrame: From baseline until end of strategy; up to 80 months after the beginning of the study
Secondary outcomes:
measure: Assessment of Quality of life (QoL)
timeFrame: From baseline until end of strategy; up to 80 months after the beginning of the study
measure: Overall Survival (OS)
timeFrame: Up to 80 months after the beginning of the study
measure: Time to Failure of Strategy (TFS)
timeFrame: Up to 80 months after the beginning of the study
measure: Progression-free survival (PFS) per sequence of therapy
timeFrame: Up to 80 months after the beginning of the study
measure: Tumor Response Rate (RR)
timeFrame: From baseline until end of strategy; up to 80 months after the beginning of the study
measure: Curative salvage surgery rate
timeFrame: From baseline until end of strategy; up to 80 months after the beginning of the study
measure: Safety profile of each treatment sequence
timeFrame: From study entry to 1 month after last study drug administration; up to 80 months after the beginning of the study
Other outcomes:
Locations:
city: Annecy
country: France
facility: Centre Hospitalier Annecy Gennevois
city: Auxerre
country: France
facility: Centre hospitalier Auxerre
city: Caen
country: France
facility: Centre François Baclesse
city: Cannes
country: France
facility: Centre Hospitalier
city: Chateauroux
country: France
facility: Centre Hospitalier Chateauroux
city: Colmar
country: France
facility: Hospices Civils de Colmar
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Dax
country: France
facility: Centre Hospitalier
city: Dijon
country: France
facility: Centre d'oncologie et de radiothérapie du Parc
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: La Roche sur Yon
country: France
facility: CHD Vendée
city: Le Coudray
country: France
facility: Hôpital Louis Pasteur
city: Le Havre
country: France
facility: Hôpital Privé de l'Estuaire
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Levallois Perret
country: France
facility: Institut d'oncoloige Hartmann
city: Levallois Perret
country: France
facility: Institut Hospitalier Franco-Britannique
city: Lille
country: France
facility: Centre Bourgogne
city: Lorient
country: France
facility: Centre Hospitalier de Bretagne Sud
city: Lyon
country: France
facility: Hôpital Privé Jean Mermoz
city: Marseille
country: France
facility: Hôpital Européen
city: Marseille
country: France
facility: Hôpital Nord
city: Mont de Marsan
country: France
facility: Centre Hospitalier Layné
city: Nancy
country: France
facility: Centre d'oncologie de Gentilly
city: Nantes
country: France
facility: Centre Sainte Catherine de Sienne
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital Pitié-Salpêtrière
city: Paris
country: France
facility: Hôpital Saint-Antoine
city: Paris
country: France
facility: Hôpital Saint-Joseph
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hôpital Tenon
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Périgueux
country: France
facility: Hôpital Périgueux
city: Saint Cyr sur Loire
country: France
facility: Clinique de l'Alliance
city: Saint Malo
country: France
facility: Hôpital Broussais - CH Saint Malo
city: Saint Priest en Jarez
country: France
facility: Institut de Cancérologie Lucien Neuwirth
city: Saint-Brieuc
country: France
facility: Clinique Armoricaine de Radiologie
city: Senlis
country: France
facility: CH de Senlis
city: Sens
country: France
facility: Centre Hospitalier de Sens
city: Strasbourg
country: France
facility: Clinique Sainte-Anne
city: Suresnes
country: France
facility: Hôpital Foch
city: Thonon Les Bains
country: France
facility: Hôpitaux du Léman
city: Toulon
country: France
facility: Hôpital Sainte Musse
city: Valence
country: France
facility: Clinique Générale
city: Villeneuve-d'Ascq
country: France
facility: Institut de Cancérologie
city: Cork
country: Ireland
facility: Bon Secours Hospital
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: Adelaide & Meath Hospital Dublin ( AMNCH)
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Dublin
country: Ireland
facility: Mater Private Hospital
city: Dublin
country: Ireland
facility: St. James's Hospital
city: Dublin
country: Ireland
facility: St. Vincent's University Hospital
city: Galway
country: Ireland
facility: University Hospital Galway
city: Waterford
country: Ireland
facility: University Hospital Waterford
city: Ramat Gan
country: Israel
facility: Sheba Tel Hashomer
city: Zerifin
country: Israel
facility: Assaf Harofeh Medical Center
Study officials:
affiliation: Institut Hospitalier Franco-Britannique
name: Benoist Chibaudel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chibaudel B, Bonnetain F, Tournigand C, de Larauze MH, de Gramont A, Laurent-Puig P, Paget J, Hadengue A, Notelet D, Benetkiewicz M, Andre T, de Gramont A. STRATEGIC-1: A multiple-lines, randomized, open-label GERCOR phase III study in patients with unresectable wild-type RAS metastatic colorectal cancer. BMC Cancer. 2015 Jul 4;15:496. doi: 10.1186/s12885-015-1503-7.