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

NCT01771458 | Completed Phase 2 DMC

• 1 other identifier: IC 2012-04
• Study Type: interventional
• Target: 742
• Locations: 1 country
• Sites: 8

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

Keywords

Metastatic/Reccurent; Solid Tumor; Refractory; Molecular profile; Targeted treatment

Outcome Measures

Primary Outcomes (1)

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

  Tumor evaluation according to RECIST 1.1 criteria (every 2 months)

Secondary Outcomes (8)

• 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.

Study Arms (2)

Standard chemotherapy

ACTIVE COMPARATOR

Treatment choice is based on Investigator decision.

Procedure: Tumor biopsy; Drug: Standard Chemotherapy

Personalized treatment

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

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

Interventions

Targeted therapy based on molecular profiling : Imatinib DRUG

Personalized treatment

Tumor biopsy PROCEDURE

Personalized treatment; Standard chemotherapy

Standard Chemotherapy DRUG

Also known as: Based on each investigator choice

Standard chemotherapy

Targeted therapy based on molecular profiling : Everolimus DRUG

Personalized treatment

Targeted therapy based on molecular profiling : Vemurafenib DRUG

Personalized treatment

Targeted therapy based on molecular profiling : Sorafenib DRUG

Personalized treatment

Targeted therapy based on molecular profiling : Erlotinib DRUG

Personalized treatment

Targeted therapy based on molecular profiling : Lapatinib + Trastuzumab DRUG

Personalized treatment

Targeted therapy based on molecular profiling : Dasatinib DRUG

Personalized treatment

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

Personalized treatment

Targeted therapy based on molecular profiling : Abiraterone DRUG

Personalized treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Institut Curie: lead

Study Sites (8)

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

Dijon, 21079, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

Insitut Curie

Paris, 75248, France

Location

Institut Curie Hopital Rene Huguenin

Saint-Cloud, 92210, France

Location

Institut de cancérologie de l'Ouest Centre René Gauducheau

Saint-Herblain, 44000, France

Location

Institut Claudius Régaud

Toulouse, 31052, France

Location

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, 54500, France

Location

Related Publications (2)

• 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.

  PMID: 27993804 RESULT

• 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.

  PMID: 26342236 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Trastuzumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Christophe LE TOURNEAU, MD

  Institut Curie

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2012
• First Posted: January 18, 2013
• Study Start: October 1, 2012
• Primary Completion: October 1, 2016
• Study Completion: December 1, 2016
• Last Updated: November 24, 2025

Record last verified: 2025-11

Locations

FR (8)