A Randomized Phase II Trial Comparing Therapy Based on Tumor Molecular Profiling Versus Conventional Therapy in Patients With Refractory Cancer
This trial is active, not recruiting.
|Condition||reccurent/metastatic solid tumor disease|
|Treatments||targeted therapy based on molecular profiling : imatinib, tumor biopsy, standard chemotherapy, targeted therapy based on molecular profiling : everolimus, targeted therapy based on molecular profiling : vemurafenib, targeted therapy based on molecular profiling : sorafenib, targeted therapy based on molecular profiling : erlotinib, targeted therapy based on molecular profiling : lapatinib + trastuzumab, targeted therapy based on molecular profiling : dasatinib, targeted therapy based on molecular profiling : tamoxifen (or letrozole if contra-indication), targeted therapy based on molecular profiling : abiraterone|
|Start date||October 2012|
|End date||October 2016|
|Trial size||742 participants|
|Trial identifier||NCT01771458, IC 2012-04|
SHIVA is a proof of concept randomized phase II trial which compares two treatment strategies for patients with refractory cancer.
From a tumor biopsy, a molecular profile of the disease is established (mutations, amplifications, hormone receptor status). If a molecular abnormality is identified for which an approved targeted agent is available, patients are randomized randomized between two arms:
- Targeted therapy based on the molecular profile
- Conventional therapy based on investigator's choice.
A cross-over is proposed at disease progression.
|United States||No locations recruiting|
|Other countries||No locations recruiting|
|Dijon, France||Centre régional de lutte contre le cancer de Bourgogne Georges François Leclerc||no longer recruiting|
|Lyon, France||Centre Leon Berard||no longer recruiting|
|Marseille, France||Institut Paoli Calmettes||no longer recruiting|
|Paris, France||Insitut Curie||no longer recruiting|
|Saint-cloud, France||Institut Curie Hopital Rene Huguenin||no longer recruiting|
|Saint-herblain, France||Institut de cancérologie de l'Ouest Centre René Gauducheau||no longer recruiting|
|Toulouse, France||Institut Claudius Régaud||no longer recruiting|
|Vandoeuvre Les Nancy, France||Centre Alexis Vautrin||no longer recruiting|
|Endpoint classification||efficacy study|
|Intervention model||crossover assignment|
Patient's progression free survival (according RECIST 1.1) of targeted therapy based on molecular profiling versus conventional chemotherapy.
Overall response rate (ORR)
Overall Survival (OS)
Treatments side effects assessement according to the NCI CTCAE v4.03 scale.
Treatment effect variations as defined by tumor growth according to the altered signaling pathway
Patient's progression free survival (according RECIST 1.1) of targeted therapy based on molecular profiling versus conventional chemotherapy after cross-over.
Evaluation of the ability of ctDNA to early predict treament efficacy
Evaluation of the medico-economic impact of the experimental strategy
Technical feasability of the SHIVA trial: number of screened patient compared to number of patients elligible to randomization.
Male or female participants at least 18 years old.
- Patient with recurrent/metastatic solid tumor who failed or are not candidate for treatments usually proposed in first intentions and for whom a prospective clinical trial has been indicated in a tumor board
- ECOG performance status of 0 or 1
- Biopsiable disease (tumor biopsy mandatory for tumor profiling). The biopsy can be performed when patients are being treated with standard therapy for their recurrent/metastatic cancer if it is not planned to treat them with molecularly targeted agents in the future.
- Measurable disease
- Adequate renal function defined by a serum creatinine <1.5xUNL (upper normal limit)
- Adequate liver function test defined by SGOT & SGPT <3xUNL (5xUNL in case of liver metastases), and bilirubin level <1.5xUNL
- Adequate bone marrow function defined by platelets >100,000/mm3, hemoglobin >10 g/dL, and neutrophils >1,000/mm3
- Patients must be affiliated to the French Social Security System
- Signed informed consent
- For female of child-bearing potential: a negative pregnancy test <72 hours before starting study treatment is required. If sexually active, female of childbearing potential must use "highly effective" methods of contraception for the study duration and for 3 months following the last treatment
- For male of reproductive potential: any sexually active male patient must use a condom while on study treatment and for 3 months following the last treatment
- Agreement to send the CD-ROMs of imaging for central review
- Patients who have only bone and/or brain metastases
- Patients whose brain metastases have not been controlled for >3 months
- Patient participating in another clinical trial with an experimental drug
- Patients who are candidate to receive a molecularly targeted agent that is approved for their disease
- Anticoagulation with anti-vitamin K (Low Molecular Weight Heparin [LMWH] is allowed)
- Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, including uncontrolled diabetes, cardiac disease, uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infection within one year, chronic liver or renal disease, active gastrointestinal tract ulceration, severely impaired lung function
- Pregnant and/or breastfeeding women
- Individually deprived of liberty or placed under the authority of a tutor
- Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Known HIV, HBV, or HCV infection Eligibility criteria for the randomized part :
- Identification of tumor molecular abnormalities for which the Therapeutic Decision Committee (TDC) recommends a molecularly targeted therapy available in the context of the trial (even if the molecular profile is incomplete)
- Therapy recommended by the TDC is not approved for the patient's disease
- ECOG performance status of 0 or 1
- Adequate renal function defined by a serum creatinine <1.5xUNL
- Adequate liver function tests defined by SGOT & SGPT <3xUNL (5xUNL in case of liver metastases), and bilirubin level <1.5xUNL
- Adequate bone marrow function defined by platelets >100,000/mm3, hemoglobin >8 g/dL, and neutrophils >1,000/mm3
- Albumin, LDH and number of metastatic sites have been documented (in order to determine the RMH prognostic score)
- LVEF >50%
- QTc <480 ms on ECG
|Official title||A Randomized Proof-of-concept Phase II Trial Comparing Therapy Based on Tumor Molecular Profiling Versus Conventional Therapy in Patients With Refractory Cancer.|
|Principal investigator||Christophe LE TOURNEAU, MD|
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