Multi-Line Therapy Trial in Unresectable Metastatic Colorectal Cancer

NCT ID: NCT01910610

Last Updated: 2024-03-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

464 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-10-30

Study Completion Date

2024-12-31

Brief Summary

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

Detailed Description

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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.

Conditions

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Colorectal Cancer Metastatic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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STRATEGY A

FOLFIRI-cetuximab, followed by oxaliplatin-based chemotherapy with bevacizumab

Group Type EXPERIMENTAL

FOLFIRI-cetuximab

Intervention Type BIOLOGICAL

mFOLFOX6-bevacizumab

Intervention Type BIOLOGICAL

XELOX + bevacizumab

Intervention Type BIOLOGICAL

STRATEGY B

OPTIMOX-bevacizumab, followed by irinotecan-based chemotherapy with bevacizumab, followed by anti-EGFR mab with or without irinotecan

Group Type EXPERIMENTAL

OPTIMOX-bevacizumab

Intervention Type BIOLOGICAL

irinotecan-based chemo + bevacizumab

Intervention Type BIOLOGICAL

Anti-EGFR agent (cetuximab +/- irinotecan or panitumumab)

Intervention Type BIOLOGICAL

XELOX + bevacizumab

Intervention Type BIOLOGICAL

Interventions

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FOLFIRI-cetuximab

Intervention Type BIOLOGICAL

mFOLFOX6-bevacizumab

Intervention Type BIOLOGICAL

OPTIMOX-bevacizumab

Intervention Type BIOLOGICAL

irinotecan-based chemo + bevacizumab

Intervention Type BIOLOGICAL

Anti-EGFR agent (cetuximab +/- irinotecan or panitumumab)

Intervention Type BIOLOGICAL

XELOX + bevacizumab

Intervention Type BIOLOGICAL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role collaborator

GERCOR - Multidisciplinary Oncology Cooperative Group

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Benoist Chibaudel, MD

Role: PRINCIPAL_INVESTIGATOR

Institut Hospitalier Franco-Britannique

Locations

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Centre Hospitalier Annecy Gennevois

Annecy, , France

Site Status

Centre hospitalier Auxerre

Auxerre, , France

Site Status

Centre François Baclesse

Caen, , France

Site Status

Centre Hospitalier

Cannes, , France

Site Status

Centre Hospitalier Chateauroux

Châteauroux, , France

Site Status

Hospices Civils de Colmar

Colmar, , France

Site Status

Hôpital Henri Mondor

Créteil, , France

Site Status

Centre Hospitalier

Dax, , France

Site Status

Centre d'oncologie et de radiothérapie du Parc

Dijon, , France

Site Status

Centre Georges François Leclerc

Dijon, , France

Site Status

CHD Vendée

La Roche-sur-Yon, , France

Site Status

Hôpital Louis Pasteur

Le Coudray, , France

Site Status

Hôpital Privé de l'Estuaire

Le Havre, , France

Site Status

Clinique Victor Hugo

Le Mans, , France

Site Status

Institut d'oncoloige Hartmann

Levallois-Perret, , France

Site Status

Institut Hospitalier Franco-Britannique

Levallois-Perret, , France

Site Status

Centre Bourgogne

Lille, , France

Site Status

Centre Hospitalier de Bretagne Sud

Lorient, , France

Site Status

Hôpital Privé Jean Mermoz

Lyon, , France

Site Status

Hôpital Européen

Marseille, , France

Site Status

Hôpital Nord

Marseille, , France

Site Status

Centre Hospitalier Layné

Mont-de-Marsan, , France

Site Status

Centre d'oncologie de Gentilly

Nancy, , France

Site Status

Centre Sainte Catherine de Sienne

Nantes, , France

Site Status

Hôpital Cochin

Paris, , France

Site Status

Hôpital Pitié-Salpêtrière

Paris, , France

Site Status

Hôpital Saint-Antoine

Paris, , France

Site Status

Hôpital Saint-Joseph

Paris, , France

Site Status

Hôpital Saint-Louis

Paris, , France

Site Status

Hôpital Tenon

Paris, , France

Site Status

Institut Mutualiste Montsouris

Paris, , France

Site Status

Hôpital Périgueux

Périgueux, , France

Site Status

Clinique Armoricaine de Radiologie

Saint-Brieuc, , France

Site Status

Clinique de l'Alliance

Saint-Cyr-sur-Loire, , France

Site Status

Institut de Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, , France

Site Status

CH de Senlis

Senlis, , France

Site Status

Centre Hospitalier de Sens

Sens, , France

Site Status

Hôpital Broussais - CH Saint Malo

St-Malo, , France

Site Status

Clinique Sainte-Anne

Strasbourg, , France

Site Status

Hôpital Foch

Suresnes, , France

Site Status

Hôpitaux du Léman

Thonon-les-Bains, , France

Site Status

Hôpital Sainte Musse

Toulon, , France

Site Status

Clinique Générale

Valence, , France

Site Status

Institut de Cancérologie

Villeneuve-d'Ascq, , France

Site Status

Bon Secours Hospital

Cork, , Ireland

Site Status

Cork University Hospital

Cork, , Ireland

Site Status

Adelaide & Meath Hospital Dublin ( AMNCH)

Dublin, , Ireland

Site Status

Beaumont Hospital

Dublin, , Ireland

Site Status

Mater Misericordiae University Hospital

Dublin, , Ireland

Site Status

Mater Private Hospital

Dublin, , Ireland

Site Status

St. James's Hospital

Dublin, , Ireland

Site Status

St. Vincent's University Hospital

Dublin, , Ireland

Site Status

University Hospital Galway

Galway, , Ireland

Site Status

University Hospital Waterford

Waterford, , Ireland

Site Status

Sheba Tel Hashomer

Ramat Gan, , Israel

Site Status

Assaf Harofeh Medical Center

Ẕerifin, , Israel

Site Status

Countries

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France Ireland Israel

References

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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.

Reference Type DERIVED
PMID: 26141683 (View on PubMed)

Other Identifiers

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2013-001928-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

STRATEGIC-1 C12- 2

Identifier Type: -

Identifier Source: org_study_id

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