Multi-Line Therapy Trial in Unresectable Metastatic Colorectal Cancer

NCT01910610 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: STRATEGIC-1 C12- 22013-001928-19
• Study Type: interventional
• Target: 464
• Locations: 3 countries
• Sites: 56

Brief Summary

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

Conditions

Colorectal Cancer Metastatic

Keywords

wild-type RAS metastatic colorectal cancer

Outcome Measures

Primary Outcomes (1)

• Duration of Disease Control (DDC)

  DDC is defined as the sum of PFS of each active treatment course planned in the treatment strategy. DDC excludes 1) intervals between disease progression and re-initiation of treatment, and 2) PFS of inactive treatment if PD occurs at first evaluation after treatment re-initiation (either reintroduction in a stop-and-go strategy or subsequent course of treatment in a multi-line strategy).

  From baseline until end of strategy; up to 80 months after the beginning of the study

Secondary Outcomes (7)

• Assessment of Quality of life (QoL)

  From baseline until end of strategy; up to 80 months after the beginning of the study

• Overall Survival (OS)

  Up to 80 months after the beginning of the study

• Time to Failure of Strategy (TFS)

  Up to 80 months after the beginning of the study

• Progression-free survival (PFS) per sequence of therapy

  Up to 80 months after the beginning of the study

• Tumor Response Rate (RR)

  From baseline until end of strategy; up to 80 months after the beginning of the study

Study Arms (2)

STRATEGY A

EXPERIMENTAL

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

Biological: FOLFIRI-cetuximab; Biological: mFOLFOX6-bevacizumab; Biological: XELOX + bevacizumab

STRATEGY B

EXPERIMENTAL

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

Biological: OPTIMOX-bevacizumab; Biological: irinotecan-based chemo + bevacizumab; Biological: Anti-EGFR agent (cetuximab +/- irinotecan or panitumumab); Biological: XELOX + bevacizumab

Interventions

FOLFIRI-cetuximab BIOLOGICAL

STRATEGY A

mFOLFOX6-bevacizumab BIOLOGICAL

STRATEGY A

OPTIMOX-bevacizumab BIOLOGICAL

STRATEGY B

irinotecan-based chemo + bevacizumab BIOLOGICAL

STRATEGY B

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

STRATEGY B

XELOX + bevacizumab BIOLOGICAL

STRATEGY A; STRATEGY B

Eligibility Criteria

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

You may qualify if:

• Signed and dated informed consent, and willing and able to comply with protocol requirements,
• Histologically proven adenocarcinoma of the colon and/or rectum,
• 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
• Metastatic disease confirmed,
• 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),
• At least one measurable or evaluable lesion as assessed by CT-scan or MRI (Magnetic Resonance Imaging) according to RECIST v1.1,
• Age ≥18 years,
• ECOG Performance status (PS) 0-2,
• Hematological status: neutrophils (ANC) ≥1.5x109/L; platelets ≥100x109/L; haemoglobin ≥9g/dL,
• Adequate renal function: serum creatinine level \<150µM,
• Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alkaline phosphatase \<5xULN,
• Proteinuria \<2+ (dipstick urinalysis) or ≤1g/24hour,
• 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,
• 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,
• Registration in a national health care system (CMU included for France).

You may not qualify if:

• 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,
• Exclusive bone metastasis,
• Uncontrolled hypercalcemia,
• Pre-existing permanent neuropathy (NCI grade ≥2),
• Uncontrolled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \>100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy,
• Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
• Treatment with any investigational medicinal product within 28 days prior to study entry,
• Other serious and uncontrolled non-malignant disease,
• Gilbert's syndrome,
• 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,
• 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,
• Pregnant or breastfeeding women,
• Patients with known allergy/hypersensitivity to any component of study drugs,
• History of arterial thrombo and/or embolic event (e.g. myocardial infarction, stroke,…) within 6 months prior to randomization,
• Chronic inflammatory bowel disease

Sponsors & Collaborators

• GERCOR - Multidisciplinary Oncology Cooperative Group: lead
• Hoffmann-La Roche: collaborator

Study Sites (56)

Centre Hospitalier Annecy Gennevois

Annecy, France

Location

Centre hospitalier Auxerre

Auxerre, France

Location

Centre François Baclesse

Caen, France

Location

Centre Hospitalier

Cannes, 06400, France

Location

Centre Hospitalier Chateauroux

Châteauroux, France

Location

Hospices Civils de Colmar

Colmar, France

Location

Hôpital Henri Mondor

Créteil, France

Location

Centre Hospitalier

Dax, 40107, France

Location

Centre d'oncologie et de radiothérapie du Parc

Dijon, France

Location

Centre Georges François Leclerc

Dijon, France

Location

CHD Vendée

La Roche-sur-Yon, France

Location

Hôpital Louis Pasteur

Le Coudray, France

Location

Hôpital Privé de l'Estuaire

Le Havre, France

Location

Clinique Victor Hugo

Le Mans, France

Location

Institut d'oncoloige Hartmann

Levallois-Perret, France

Location

Institut Hospitalier Franco-Britannique

Levallois-Perret, France

Location

Centre Bourgogne

Lille, France

Location

Centre Hospitalier de Bretagne Sud

Lorient, France

Location

Hôpital Privé Jean Mermoz

Lyon, France

Location

Hôpital Européen

Marseille, France

Location

Hôpital Nord

Marseille, France

Location

Centre Hospitalier Layné

Mont-de-Marsan, France

Location

Centre d'oncologie de Gentilly

Nancy, France

Location

Centre Sainte Catherine de Sienne

Nantes, France

Location

Hôpital Cochin

Paris, France

Location

Hôpital Pitié-Salpêtrière

Paris, France

Location

Hôpital Saint-Antoine

Paris, France

Location

Hôpital Saint-Joseph

Paris, France

Location

Hôpital Saint-Louis

Paris, France

Location

Hôpital Tenon

Paris, France

Location

Institut Mutualiste Montsouris

Paris, France

Location

Hôpital Périgueux

Périgueux, France

Location

Clinique Armoricaine de Radiologie

Saint-Brieuc, France

Location

Clinique de l'Alliance

Saint-Cyr-sur-Loire, France

Location

Institut de Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, France

Location

CH de Senlis

Senlis, France

Location

Centre Hospitalier de Sens

Sens, France

Location

Hôpital Broussais - CH Saint Malo

St-Malo, France

Location

Clinique Sainte-Anne

Strasbourg, France

Location

Hôpital Foch

Suresnes, France

Location

Hôpitaux du Léman

Thonon-les-Bains, 74200, France

Location

Hôpital Sainte Musse

Toulon, France

Location

Clinique Générale

Valence, France

Location

Institut de Cancérologie

Villeneuve-d'Ascq, 59657, France

Location

Bon Secours Hospital

Cork, Ireland

Location

Cork University Hospital

Cork, Ireland

Location

Adelaide & Meath Hospital Dublin ( AMNCH)

Dublin, Ireland

Location

Beaumont Hospital

Dublin, Ireland

Location

Mater Misericordiae University Hospital

Dublin, Ireland

Location

Mater Private Hospital

Dublin, Ireland

Location

St. James's Hospital

Dublin, Ireland

Location

St. Vincent's University Hospital

Dublin, Ireland

Location

University Hospital Galway

Galway, Ireland

Location

University Hospital Waterford

Waterford, Ireland

Location

Sheba Tel Hashomer

Ramat Gan, Israel

Location

Assaf Harofeh Medical Center

Ẕerifin, Israel

Location

Related Publications (1)

• 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.

  PMID: 26141683 DERIVED

MeSH Terms

Interventions

Bevacizumab; Panitumumab; XELOX

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Benoist Chibaudel, MD

  Institut Hospitalier Franco-Britannique

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2013
• First Posted: July 29, 2013
• Study Start: October 30, 2013
• Primary Completion: July 13, 2023
• Study Completion: December 1, 2024
• Last Updated: March 12, 2024

Record last verified: 2024-03

Locations

IL (2); FR (44); IE (10)