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

NCT ID: NCT01771458

Last Updated: 2025-11-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 742 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2016-12-31

Brief 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.

Conditions

Reccurent/Metastatic Solid Tumor Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard chemotherapy

Treatment choice is based on Investigator decision.

Group Type: ACTIVE_COMPARATOR

Tumor biopsy

Intervention Type: PROCEDURE

Standard Chemotherapy

Intervention Type: DRUG

Personalized treatment

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

Group Type: EXPERIMENTAL

Targeted therapy based on molecular profiling : Imatinib

Intervention Type: DRUG

Tumor biopsy

Intervention Type: PROCEDURE

Targeted therapy based on molecular profiling : Everolimus

Intervention Type: DRUG

Targeted therapy based on molecular profiling : Vemurafenib

Intervention Type: DRUG

Targeted therapy based on molecular profiling : Sorafenib

Intervention Type: DRUG

Targeted therapy based on molecular profiling : Erlotinib

Intervention Type: DRUG

Targeted therapy based on molecular profiling : Lapatinib + Trastuzumab

Intervention Type: DRUG

Targeted therapy based on molecular profiling : Dasatinib

Intervention Type: DRUG

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

Intervention Type: DRUG

Targeted therapy based on molecular profiling : Abiraterone

Intervention Type: DRUG

Interventions

Targeted therapy based on molecular profiling : Imatinib

Intervention Type: DRUG

Tumor biopsy

Intervention Type: PROCEDURE

Standard Chemotherapy

Intervention Type: DRUG

Targeted therapy based on molecular profiling : Everolimus

Intervention Type: DRUG

Targeted therapy based on molecular profiling : Vemurafenib

Intervention Type: DRUG

Targeted therapy based on molecular profiling : Sorafenib

Intervention Type: DRUG

Targeted therapy based on molecular profiling : Erlotinib

Intervention Type: DRUG

Targeted therapy based on molecular profiling : Lapatinib + Trastuzumab

Intervention Type: DRUG

Targeted therapy based on molecular profiling : Dasatinib

Intervention Type: DRUG

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

Intervention Type: DRUG

Targeted therapy based on molecular profiling : Abiraterone

Intervention Type: DRUG

Other Intervention Names

Based on each investigator choice

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut Curie

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christophe LE TOURNEAU, MD

Role: PRINCIPAL_INVESTIGATOR

Institut Curie

Locations

Centre régional de lutte contre le cancer de Bourgogne Georges François Leclerc

Dijon, , France

Centre Leon Berard

Lyon, , France

Institut Paoli Calmettes

Marseille, , France

Insitut Curie

Paris, , France

Institut Curie Hopital Rene Huguenin

Saint-Cloud, , France

Institut de cancérologie de l'Ouest Centre René Gauducheau

Saint-Herblain, , France

Institut Claudius Régaud

Toulouse, , France

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, , France

Countries

France

References

Belin L, Kamal M, Mauborgne C, Plancher C, Mulot F, Delord JP, Goncalves A, Gavoille C, Dubot C, Isambert N, Campone M, Tredan O, Ricci F, Alt M, Loirat D, Sablin MP, Paoletti X, Servois V, Le Tourneau C. Randomized phase II trial comparing molecularly targeted therapy based on tumor molecular profiling versus conventional therapy in patients with refractory cancer: cross-over analysis from the SHIVA trial. Ann Oncol. 2017 Mar 1;28(3):590-596. doi: 10.1093/annonc/mdw666.

Reference Type: RESULT

PMID: 27993804 (View on PubMed)

Le Tourneau C, Delord JP, Goncalves A, Gavoille C, Dubot C, Isambert N, Campone M, Tredan O, Massiani MA, Mauborgne C, Armanet S, Servant N, Bieche I, Bernard V, Gentien D, Jezequel P, Attignon V, Boyault S, Vincent-Salomon A, Servois V, Sablin MP, Kamal M, Paoletti X; SHIVA investigators. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol. 2015 Oct;16(13):1324-34. doi: 10.1016/S1470-2045(15)00188-6. Epub 2015 Sep 3.

Reference Type: DERIVED

PMID: 26342236 (View on PubMed)

Other Identifiers

IC 2012-04

Identifier Type: -

Identifier Source: org_study_id