Clinical Trials /

Multi-Line Therapy Trial in Unresectable Metastatic Colorectal Cancer

NCT01910610

Description:

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

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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.

Clinical Trial IDs

  • ORG STUDY ID: STRATEGIC-1 C12- 2
  • SECONDARY ID: 2013-001928-19
  • NCT ID: NCT01910610

Conditions

  • Colorectal Cancer Metastatic

Interventions

DrugSynonymsArms
FOLFIRI-cetuximabSTRATEGY A
mFOLFOX6-bevacizumabSTRATEGY A
OPTIMOX-bevacizumabSTRATEGY B
irinotecan-based chemo + bevacizumabSTRATEGY B
Anti-EGFR agent (cetuximab +/- irinotecan or panitumumab)STRATEGY B
XELOX + bevacizumabSTRATEGY A

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
STRATEGY AExperimentalFOLFIRI-cetuximab, followed by oxaliplatin-based chemotherapy with bevacizumab
    STRATEGY BExperimentalOPTIMOX-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
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Duration of Disease Control
      Time Frame:From baseline until end of strategy, assessed up to 80 months after the beginning of the study
      Safety Issue:
      Description:

      Secondary Outcome Measures

      Measure:Quality of life
      Time Frame:from baseline until end of strategy, assessed up to 80 months after the beginning of the study
      Safety Issue:
      Description:QoL will be considered to be improved if at least one time to QoL score deterioration (Five targeted dimensions) will be significantly longer without a significant shorter time to QoL score dimensions for other 4 targeted dimensions.
      Measure:Overall Survival
      Time Frame:time interval from randomization to the date of death from any cause. Assessed up to 80 months after the beginning of the study.
      Safety Issue:
      Description:
      Measure:Time to Failure of Strategy
      Time Frame:Assessed up to 80 months after the beginning of the study
      Safety Issue:
      Description:TFS is defined as beginning with the initiation of the strategy under investigation and ending with the first of the following events: 1) death, 2) disease progression on the last received planned sequence, 3) patient requires the addition of a new (unplanned) therapeutic agent, 4) patient experiences disease progression during a partial or complete break in therapy from initial treatment strategy and receives no further therapy within one month.
      Measure:Progression-free survival (PFS) per sequence of therapy
      Time Frame:the time interval from randomization to the date of first documented disease progression or death from any cause, whichever occurs first. Assessed up to 80 months after the beginning of the study
      Safety Issue:
      Description:
      Measure:Tumor Response Rate (RR)
      Time Frame:from baseline until end of strategy, assessed up to 80 months after the beginning of the study
      Safety Issue:
      Description:
      Measure:Curative salvage surgery rate
      Time Frame:from baseline until end of strategy, assessed up to 80 months after the beginning of the study
      Safety Issue:
      Description:
      Measure:Safety profile of each treatment sequence
      Time Frame:Assessed from study entry to 1 month after last study drug administration, assessed up to 80 months after the beginning of the study
      Safety Issue:
      Description:The study will take into account all adverse events observed during and after drug administration, with a particular interest for: Any AE Any serious AE Any serious AE related to study treatment Any NCI-CTC grade 3 or 4 AE Any AE causing discontinuation of study treatment Any AE causing a dose reduction of study medication Any AE leading to death

      Details

      Phase:Phase 3
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:GERCOR - Multidisciplinary Oncology Cooperative Group

      Trial Keywords

      • wild-type RAS metastatic colorectal cancer

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