Overview

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
Phase phase 2
Sponsor Institut Curie
Start date October 2012
End date October 2016
Trial size 742 participants
Trial identifier NCT01771458, IC 2012-04

Summary

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

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model crossover assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Treatment choice is based on Investigator decision.
tumor biopsy
standard chemotherapy Based on each investigator choice
(Experimental)
Targeted therapy based on the patient molecular profil (if there is at least one abnormality that could be targeted) Elligible therapies in this trial are : Imatinib Everolimus Vemurafenib Sorafenib Erlotinib Lapatinib Trastuzumab Dasatinib Tamoxifen (or letrozole if contra-indication) Abiraterone
targeted therapy based on molecular profiling : imatinib
tumor biopsy
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

Primary Outcomes

Measure
Patient's progression free survival (according RECIST 1.1) of targeted therapy based on molecular profiling versus conventional chemotherapy.
time frame:

Secondary Outcomes

Measure
Overall response rate (ORR)
time frame:
Overall Survival (OS)
time frame:
Treatments side effects assessement according to the NCI CTCAE v4.03 scale.
time frame:
Treatment effect variations as defined by tumor growth according to the altered signaling pathway
time frame:
Patient's progression free survival (according RECIST 1.1) of targeted therapy based on molecular profiling versus conventional chemotherapy after cross-over.
time frame:
Evaluation of the ability of ctDNA to early predict treament efficacy
time frame:
Evaluation of the medico-economic impact of the experimental strategy
time frame:
Technical feasability of the SHIVA trial: number of screened patient compared to number of patients elligible to randomization.
time frame:

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. 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 2. ECOG performance status of 0 or 1 3. 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. 4. Measurable disease 5. Adequate renal function defined by a serum creatinine <1.5xUNL (upper normal limit) 6. Adequate liver function test defined by SGOT & SGPT <3xUNL (5xUNL in case of liver metastases), and bilirubin level <1.5xUNL 7. Adequate bone marrow function defined by platelets >100,000/mm3, hemoglobin >10 g/dL, and neutrophils >1,000/mm3 8. Patients must be affiliated to the French Social Security System 9. Signed informed consent 10. 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 11. 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 12. Agreement to send the CD-ROMs of imaging for central review Exclusion Criteria: 1. Patients who have only bone and/or brain metastases 2. Patients whose brain metastases have not been controlled for >3 months 3. Patient participating in another clinical trial with an experimental drug 4. Patients who are candidate to receive a molecularly targeted agent that is approved for their disease 5. Anticoagulation with anti-vitamin K (Low Molecular Weight Heparin [LMWH] is allowed) 6. 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 7. Pregnant and/or breastfeeding women 8. Individually deprived of liberty or placed under the authority of a tutor 9. Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule 10. Known HIV, HBV, or HCV infection Eligibility criteria for the randomized part : 1. 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) 2. Therapy recommended by the TDC is not approved for the patient's disease 3. ECOG performance status of 0 or 1 4. Adequate renal function defined by a serum creatinine <1.5xUNL 5. Adequate liver function tests defined by SGOT & SGPT <3xUNL (5xUNL in case of liver metastases), and bilirubin level <1.5xUNL 6. Adequate bone marrow function defined by platelets >100,000/mm3, hemoglobin >8 g/dL, and neutrophils >1,000/mm3 7. Albumin, LDH and number of metastatic sites have been documented (in order to determine the RMH prognostic score) 8. LVEF >50% 9. QTc <480 ms on ECG

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Institut Curie.