A Randomized Phase II Trial Comparing Therapy Based on Tumor Molecular Profiling Versus Conventional Therapy in Patients With Refractory Cancer (SHIVA)

Institut Curie

Status and phase: Unknown; Phase 2

Conditions: Reccurent/Metastatic Solid Tumor Disease

Treatments: Drug: Targeted therapy based on molecular profiling : Dasatinib; Procedure: Tumor biopsy; Drug: Standard Chemotherapy; Drug: Targeted therapy based on molecular profiling : Imatinib; Drug: Targeted therapy based on molecular profiling : Vemurafenib; Drug: Targeted therapy based on molecular profiling : Abiraterone; Drug: Targeted therapy based on molecular profiling : Tamoxifen (or letrozole if contra-indication); Drug: Targeted therapy based on molecular profiling : Erlotinib; Drug: Targeted therapy based on molecular profiling : Sorafenib; Drug: Targeted therapy based on molecular profiling : Everolimus; Drug: Targeted therapy based on molecular profiling : Lapatinib + Trastuzumab

Study type: Interventional

Funder types: Other

Identifiers

NCT01771458

IC 2012-04

Details and patient eligibility

About

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.

Enrollment: 742 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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742 participants in 2 patient groups

Standard chemotherapy

Active Comparator group

Description:

Treatment choice is based on Investigator decision.

Treatment:

Drug: Standard Chemotherapy

Procedure: Tumor biopsy

Personalized treatment

Experimental group

Description:

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

Treatment:

Drug: Targeted therapy based on molecular profiling : Lapatinib + Trastuzumab

Drug: Targeted therapy based on molecular profiling : Everolimus

Drug: Targeted therapy based on molecular profiling : Erlotinib

Drug: Targeted therapy based on molecular profiling : Sorafenib

Drug: Targeted therapy based on molecular profiling : Abiraterone

Drug: Targeted therapy based on molecular profiling : Tamoxifen (or letrozole if contra-indication)

Drug: Targeted therapy based on molecular profiling : Imatinib

Drug: Targeted therapy based on molecular profiling : Dasatinib

Drug: Targeted therapy based on molecular profiling : Vemurafenib

Procedure: Tumor biopsy