Reccurent/Metastatic Solid Tumor DiseasePhase 2SHIVANCT01771458
A Randomized Phase II Trial Comparing Therapy Based on Tumor Molecular Profiling Versus Conventional Therapy in Patients With Refractory Cancer
A Phase 2 study testing Targeted therapy based on molecular profiling : Imatinib, Tumor biopsy and Standard Chemotherapy in people with Reccurent/Metastatic Solid Tumor Disease, run by Institut Curie at 8 sites in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Reccurent/Metastatic Solid Tumor Disease
- What is being tested?
- Targeted therapy based on molecular profiling : Imatinib, Tumor biopsy and Standard Chemotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 742 participants
- Where
- 8 sitesFrance
- Study dates
- Oct 2012to Dec 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
France8 sites
Centre régional de lutte contre le cancer de Bourgogne Georges François Leclerc
Dijon, 21079
Centre Leon Berard
Lyon, 69373
Institut Paoli Calmettes
Marseille, 13009
Insitut Curie
Paris, 75248
Institut Curie Hopital Rene Huguenin
Saint-Cloud, 92210
Institut de cancérologie de l'Ouest Centre René Gauducheau
Saint-Herblain, 44000
Institut Claudius Régaud
Toulouse, 31052
Centre Alexis Vautrin
Vandœuvre-lès-Nancy, 54500
About this study
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.
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
- Being tested
- 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
- Keywords
- Metastatic/Reccurent, Solid Tumor, Refractory, Molecular profile, Targeted treatment
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Targeted therapy based on molecular profiling : ImatinibDrug
Tumor biopsyProcedure or surgery
Standard ChemotherapyDrug
Also called Based on each investigator choice
Targeted therapy based on molecular profiling : EverolimusDrug
Targeted therapy based on molecular profiling : VemurafenibDrug
Targeted therapy based on molecular profiling : SorafenibDrug
Targeted therapy based on molecular profiling : ErlotinibDrug
Targeted therapy based on molecular profiling : Lapatinib + TrastuzumabDrug
Targeted therapy based on molecular profiling : DasatinibDrug
Targeted therapy based on molecular profiling : Tamoxifen (or letrozole if contra-indication)Drug
Targeted therapy based on molecular profiling : AbirateroneDrug
| Study group | Role | What they receive |
|---|---|---|
| Standard chemotherapy | Active comparator | Treatment choice is based on Investigator decision. Receives: 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 Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Tumor evaluation according to RECIST 1.1 criteria (every 2 months)
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
Evaluation of tumor growth before and during the study (according to RECIST 1.1)
Patient's progression free survival (according RECIST 1.1) of targeted therapy based on molecular profiling versus conventional chemotherapy after cross-over.
Tumor evaluation according to RECIST 1.1 criteria (every 2 months)
Evaluation of the ability of ctDNA to early predict treament efficacy
Comparing treatment efficacy to ctDNA level (before and during treatment course)
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.
Number of screened patients. Number of patient with a molecular full profil in the timeframe (4 weeks between tumor biopsy and SHIVA's committees decision).
Number of randomized patient.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2013 (estimated)
- Study startOct 2012
- Primary completionOct 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Reccurent/Metastatic Solid Tumor DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 742 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut Curie
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christophe LE TOURNEAU, MD, Principal investigator, Institut Curie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01771458
- Sponsor's protocol ID
- IC 2012-04
- Acronym
- SHIVA
- Status last verified
- Nov 2025
- First submitted
- 27 Nov 2012
- Last updated
- 24 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 27993804Le 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.
PubMed 26342236
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01771458
- Acronym / sponsor ID
- SHIVA / IC 2012-04
- Conditions
- Reccurent/Metastatic Solid Tumor Disease
- Keywords
- Metastatic/Reccurent, Solid Tumor, Refractory, Molecular profile, Targeted treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 742 participants (actual)
- Lead sponsor
- Institut CurieUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- Oct 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 18 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard chemotherapy | Active comparator | Procedure: Tumor biopsy, Drug: Standard ChemotherapyTreatment choice is based on Investigator decision. |
| Personalized treatment | Experimental | 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 : AbirateroneTargeted 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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)
Key exclusion criteria (20 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Targeted therapy based on molecular profiling : Imatinib | Drug | Personalized treatment |
| Tumor biopsy | Procedure or surgery | Personalized treatment, Standard chemotherapy |
| Standard ChemotherapyAlso: Based on each investigator choice | Drug | 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 |
Primary outcome
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)
8 secondary outcomes
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2025.
- Results publication: PubMed 27993804Belin 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.
- Derived from this study: PubMed 26342236Le 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christophe LE TOURNEAU, MD principal investigator
Institut Curie
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Targeted therapy based on molecular profiling : Imatinib, Tumor biopsy and Standard Chemotherapy in people with Reccurent/Metastatic Solid Tumor Disease, run by Institut Curie at 8 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patient's progression free survival (according RECIST 1.1) of targeted therapy based on molecular profiling versus conventional chemotherapy.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01771458, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2025.