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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Institut Curie
Sponsor:
Information provided by (Responsible Party):
Institut Curie
ClinicalTrials.gov Identifier:
NCT01771458
First received: November 27, 2012
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Reccurent/Metastatic Solid Tumor Disease
Drug: Targeted therapy based on molecular profiling : Imatinib
Procedure: Tumor biopsy
Drug: Standard Chemotherapy
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
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Institut Curie:

Primary Outcome Measures:
  • 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 Outcome Measures:
  • 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.



Estimated Enrollment: 1000
Study Start Date: October 2012
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard chemotherapy
Treatment choice is based on Investigator decision.
Procedure: Tumor biopsy Drug: Standard Chemotherapy
Other Name: Based on each investigator choice
Experimental: 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

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01771458

Contacts
Contact: Patricia TRESCA, MD patricia.tresca@curie.net

Locations
France
Centre régional de lutte contre le cancer de Bourgogne Georges François Leclerc Not yet recruiting
Dijon, France, 21079
Contact: Nicolas ISAMBERT, MD         
Principal Investigator: Nicolas ISAMBERT, MD         
Centre Leon Berard Not yet recruiting
Lyon, France, 69373
Contact: Olivier TREDAN, MD         
Principal Investigator: Olivier TREDAN, MD         
Institut Paoli Calmettes Not yet recruiting
Marseille, France, 13009
Contact: Anthony GONCALVES, MD         
Principal Investigator: Anthony GONCALVES, MD         
Insitut Curie Recruiting
Paris, France, 75248
Contact: Christophe Le Tourneau, MD    +33 1 44 32 44 07      
Sub-Investigator: Christophe Le Tourneau, MD         
Institut Curie Hopital Rene Huguenin Recruiting
Saint-cloud, France, 92210
Contact: Emmanuel MITRY, DOCTOR         
Principal Investigator: Emmanuel MITRY, MD         
Institut de cancérologie de l'Ouest Centre René Gauducheau Not yet recruiting
Saint-herblain, France, 44000
Contact: Mario CAMPONE, DOCTOR         
Principal Investigator: Mario CAMPONE, MD         
Institut Claudius Régaud Not yet recruiting
Toulouse, France, 31052
Contact: Jean-Pierre DELORD, MD         
Principal Investigator: Jean-Pierre DELORD, MD         
Centre Alexis Vautrin Not yet recruiting
Vandoeuvre Les Nancy, France, 54500
Contact: Céline GAVOILLE, MD         
Principal Investigator: Céline GAVOILLE, MD         
Sponsors and Collaborators
Institut Curie
Investigators
Principal Investigator: Christophe LE TOURNEAU, MD Institut Curie
  More Information

No publications provided

Responsible Party: Institut Curie
ClinicalTrials.gov Identifier: NCT01771458     History of Changes
Other Study ID Numbers: IC 2012-04
Study First Received: November 27, 2012
Last Updated: March 3, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Institut Curie:
Metastatic/Reccurent
Solid Tumor
Refractory
Molecular profile
Targeted treatment

Additional relevant MeSH terms:
Neoplasms
Dasatinib
Erlotinib
Everolimus
Lapatinib
Letrozole
Sorafenib
Tamoxifen
Trastuzumab
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Aromatase Inhibitors
Bone Density Conservation Agents
Enzyme Inhibitors
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Selective Estrogen Receptor Modulators
Therapeutic Uses

ClinicalTrials.gov processed this record on November 23, 2014