Clinical trial NCT01771458: A Randomized Phase II Trial Comparing Therapy Based on Tumor Molecular Profiling Versus Conventional Therapy in Patients With Refractory Cancer
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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Reccurent/Metastatic Solid Tumor Disease
Keywords: Metastatic/Reccurent
Solid Tumor
Refractory
Molecular profile
Targeted treatment
Lead sponsor: Institut Curie
Sponsor class: OTHER
First posted: 2013-01-18
Enrollment: 742
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Patient's progression free survival (according RECIST 1.1) of targeted therapy based on molecular profiling versus conventional chemotherapy.
Secondary outcomes:
measure: Overall response rate (ORR)
measure: Overall Survival (OS)
measure: Treatments side effects assessement according to the NCI CTCAE v4.03 scale.
measure: Treatment effect variations as defined by tumor growth according to the altered signaling pathway
measure: Patient's progression free survival (according RECIST 1.1) of targeted therapy based on molecular profiling versus conventional chemotherapy after cross-over.
measure: Evaluation of the ability of ctDNA to early predict treament efficacy
measure: Evaluation of the medico-economic impact of the experimental strategy
measure: Technical feasability of the SHIVA trial: number of screened patient compared to number of patients elligible to randomization.
Other outcomes:
Locations:
city: Dijon
country: France
facility: Centre régional de lutte contre le cancer de Bourgogne Georges François Leclerc
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Paris
country: France
facility: Insitut Curie
city: Saint-cloud
country: France
facility: Institut Curie Hopital Rene Huguenin
city: Saint-herblain
country: France
facility: Institut de cancérologie de l'Ouest Centre René Gauducheau
city: Toulouse
country: France
facility: Institut Claudius Régaud
city: Vandoeuvre Les Nancy
country: France
facility: Centre Alexis Vautrin
Study officials:
affiliation: Institut Curie
name: Christophe LE TOURNEAU, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.