Adapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: MyOwnSpecificTreatment (MOST plus)

February 9, 2024 updated by: Centre Leon Berard

A Two-period, Multicenter, Randomized, Open-label, Phase II Study Evaluating the Clinical Benefit of a Maintenance Treatment Targeting Tumor Molecular Alterations in Patients With Progressive Locally-advanced or Metastatic Solid Tumors

The MOST Plus study is a two-period phase II clinical trial, conducted in patients with all types of progressive solid tumors after at least 1 prior systemic treatment regimen for advanced disease (in the absence of a validated second line therapy).

The main goal of this study is to evaluate for these patients the clinical benefit of a maintenance treatment in patients with stable disease (SD) after induction treatment with a selected therapy (Molecular Targeted Therapy (MTT) or with SD, partial response (PR) or complete reponse (CR) with Immunotherapy (IT)).

For MTT, the first period of this trial (induction period) will enable to establish whether the identification of genomic alterations in genes encoding for "actionable" targets in the tumor cells, regardless of the histological subtype, can be used to select efficient treatment targeting the pathway activated by the mutation.

For Immunotherapy, induction period with durvalumab + tremelimumab is expected to be an innovative therapy for an efficient tumor control and may allow to identify types of cancer or molecular types of cancer that are more receptive to immunotherapy.

For all treatments, the second period (maintenance period) will use a randomized design to evaluate the clinical benefit of a maintenance treatment with the targeted therapy or immunotherapy selected based on tumor molecular profile in patients treated by MTT with SD and in patients treated by IT with SD, PR or CR.

Each patient enrolled will receive the matching targeted therapy during 12 weeks (MTT) or 52 weeks (IT). At the end of this induction period:

MTT cohorts :

  • patients with a tumor response (CR: complete response or PR: partial response) will continue the targeted therapy,
  • patients in progression will discontinue the targeted therapy and will be withdrawn from study and oriented towards standard treatments
  • patients with a stable disease at 12 weeks will be randomized in order to determine if they continue or stop the therapy.

IT cohort :

- patients with SD, PR or CR at 52 weeks will be randomized in order to determine if they continue or stop the therapy.

For each MTT treatment group: ~80 patients treated in the first step (induction period), 50 patients randomized in the second step (maintenance period, 25 patients per arm).

For IT treatment group: ~125 patients treated in the first step (induction period), 50 patients randomized in the second step (maintenance period, 25 patients per arm).

In total (for 7 treatment groups): ~ 900 patients treated in the induction period and 350 patients randomized in maintenance period.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

900

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Bordeaux, France, 33076
        • Recruiting
        • Institut Bergonié
        • Contact:
        • Sub-Investigator:
          • Mathilde CABART
        • Sub-Investigator:
          • Guilhem ROUBAUD
        • Sub-Investigator:
          • Yann GODBERT
        • Principal Investigator:
          • Antoine Italiano
        • Sub-Investigator:
          • Maud TOULMONDE
        • Sub-Investigator:
          • Kevin BOURCIER
        • Sub-Investigator:
          • Sophie COUSIN
      • Lyon, France, 69373
        • Recruiting
        • Centre Leon Berard
        • Sub-Investigator:
          • Mehdi BRAHMI
        • Sub-Investigator:
          • Anne-Sophie MICHALLET
        • Sub-Investigator:
          • Thomas BACHELOT
        • Sub-Investigator:
          • Helen BOYLE
        • Sub-Investigator:
          • Aude FLECHON
        • Sub-Investigator:
          • Christelle DE LA FOUCHARDIERE
        • Sub-Investigator:
          • Pierre-Etienne HEUDEL
        • Sub-Investigator:
          • Pierre SAINTIGNY
        • Sub-Investigator:
          • Olivier TREDAN
        • Sub-Investigator:
          • Philippe TOUSSAINT
        • Sub-Investigator:
          • Alice BONNEVILLE-LEVARD
        • Contact:
        • Sub-Investigator:
          • Virginie AVRILLON
        • Sub-Investigator:
          • Christophe BERGERON
        • Sub-Investigator:
          • Pierre BIRON
        • Sub-Investigator:
          • Philippe CASSIER
        • Sub-Investigator:
          • Patrick COMBEMALE
        • Sub-Investigator:
          • Maria CHELGHOUM
        • Sub-Investigator:
          • Françoise DESSEIGNE
        • Sub-Investigator:
          • Cécile FAURE-CONTER
        • Sub-Investigator:
          • Jérome FAYETTE
        • Sub-Investigator:
          • Didier FRAPPAZ
        • Sub-Investigator:
          • Pierre GUIBERT
        • Sub-Investigator:
          • Eve-Marie NEIDHARDT
        • Sub-Investigator:
          • Maurice PEROL
        • Sub-Investigator:
          • Stéphane DEPIL
        • Sub-Investigator:
          • Olfa DERBEL
        • Sub-Investigator:
          • Nathalie MARQUES
        • Sub-Investigator:
          • Matthieu SARABI
        • Sub-Investigator:
          • Nadège CORRADINI
        • Sub-Investigator:
          • Louis DOUBLET
        • Sub-Investigator:
          • Lauriane EBERST
        • Sub-Investigator:
          • Sylvie NEGRIER
        • Sub-Investigator:
          • Katell MICHAUX
        • Sub-Investigator:
          • Juliette REURE
        • Sub-Investigator:
          • Pauline ROCHEFORT
        • Principal Investigator:
          • Jean-Yves Blay, MD
        • Sub-Investigator:
          • Armelle DUFRESNE
        • Sub-Investigator:
          • Isabelle RAY-COQUARD
      • Lyon, France, 69495
        • Recruiting
        • Centre Hospitalier Lyon Sud
        • Contact:
        • Principal Investigator:
          • Benoit You
        • Sub-Investigator:
          • Nathalie BONNIN
        • Sub-Investigator:
          • Marion CHAUVENET
        • Sub-Investigator:
          • Claire FALANDRY
        • Sub-Investigator:
          • Gilles FREYER
        • Sub-Investigator:
          • Olivia LE SAUX
        • Sub-Investigator:
          • Denis MAILLET
        • Sub-Investigator:
          • Julien PERON
        • Sub-Investigator:
          • Sophie TARTAS
        • Sub-Investigator:
          • Véronique TRILLET-LENOIR
      • Marseille, France, 13273
        • Recruiting
        • Institut Paoli Calmettes
        • Sub-Investigator:
          • Slimane DERMECHE
        • Sub-Investigator:
          • Thibaud VALENTIN
        • Sub-Investigator:
          • Loïc MOUREY
        • Sub-Investigator:
          • Audrey MONNEUR
        • Sub-Investigator:
          • Simon LAUNAY
        • Sub-Investigator:
          • Frédéric VIRET
        • Contact:
        • Principal Investigator:
          • François BERTUCCI
        • Sub-Investigator:
          • Jean-Marc EXTRA
        • Sub-Investigator:
          • Anthony GONCALVES
        • Sub-Investigator:
          • Gwenaëlle GRAVIS-MESCAM
        • Sub-Investigator:
          • Anne MADROSZYK-FLANDIN
        • Sub-Investigator:
          • Jean-Luc RAOUL
        • Sub-Investigator:
          • Delphine PERROT
        • Sub-Investigator:
          • Magali PROVENSAL
        • Sub-Investigator:
          • Carole TARPIN
        • Sub-Investigator:
          • Louis TASSY
        • Sub-Investigator:
          • Maria Antonietta CAPPIELLO
        • Sub-Investigator:
          • Frederique ROUSSEAU
        • Sub-Investigator:
          • Nicolas MEYER
        • Sub-Investigator:
          • Elisabeth MOYAL
        • Sub-Investigator:
          • Roxana Maria RADUT
        • Sub-Investigator:
          • Henri ROCHE
        • Sub-Investigator:
          • Sarah ZAHI
        • Sub-Investigator:
          • Marine GILABERT
        • Sub-Investigator:
          • Erika LOIR
        • Sub-Investigator:
          • Pauline REIS
      • Paris, France, 75248
        • Recruiting
        • Institut Curie
        • Contact:
        • Sub-Investigator:
          • Philippe BEUZEBOC
        • Sub-Investigator:
          • François-Clément BIDARD
        • Sub-Investigator:
          • Bruno BUECHER
        • Sub-Investigator:
          • Paul-Henri COTTU
        • Sub-Investigator:
          • Catherine DANIEL
        • Sub-Investigator:
          • Véronique DIERAS
        • Sub-Investigator:
          • Valérie LAURENCE
        • Sub-Investigator:
          • Alain LIVARTOWSKI
        • Sub-Investigator:
          • Jean-Yves PIERGA
        • Sub-Investigator:
          • Marie ALT
        • Sub-Investigator:
          • Delphine LOIRAT
        • Sub-Investigator:
          • Marie-Paule SABLIN
        • Sub-Investigator:
          • Mustapha ZOUBIR
        • Sub-Investigator:
          • Francesco RICCI
        • Sub-Investigator:
          • Emanuela ROMANO
        • Sub-Investigator:
          • Olivier COLLARD
        • Sub-Investigator:
          • Edith BORCOMAN
        • Sub-Investigator:
          • Ségolène HESCOT
        • Sub-Investigator:
          • Nouritza TOROSSIAN
        • Principal Investigator:
          • Christophe LE TOURNEAU, MD
      • Strasbourg, France, 67033
        • Recruiting
        • Institut de Cancerologie de Strasbourg Europe
        • Principal Investigator:
          • Lauriane EBERST, MD
        • Sub-Investigator:
          • Philippe BARTHELEMY, MD
        • Sub-Investigator:
          • Christine BELLETIER, MD
        • Sub-Investigator:
          • Meher BEN ABDELGHANI, MD
        • Sub-Investigator:
          • Mickael BURGY, MD
        • Sub-Investigator:
          • Sophie MARTIN, MD
        • Sub-Investigator:
          • Roland SCHOTT, MD
        • Sub-Investigator:
          • Pascale CHIAPPA, MD
        • Sub-Investigator:
          • Justine GANTZER, MD
        • Sub-Investigator:
          • Philippe TRENSZ, MD
        • Contact:
        • Sub-Investigator:
          • Laura BENDER, MD
        • Sub-Investigator:
          • Hélène CARINATO, MD
      • Toulouse, France, 31059
        • Recruiting
        • Institut Claudius Regaud
        • Sub-Investigator:
          • Thibaud VALENTIN
        • Sub-Investigator:
          • Loïc MOUREY
        • Sub-Investigator:
          • Damien POUESSEL
        • Sub-Investigator:
          • Iphigénie KORAKIS
        • Sub-Investigator:
          • Christine CHEVREAU
        • Sub-Investigator:
          • Nicolas MEYER
        • Sub-Investigator:
          • Elisabeth MOYAL
        • Sub-Investigator:
          • Henri ROCHE
        • Contact:
        • Principal Investigator:
          • Carlos-Alberto GOMEZ-ROCA
        • Sub-Investigator:
          • Ewa-Anna COTTURA
        • Sub-Investigator:
          • Florence DALENC
        • Sub-Investigator:
          • Jean-Pierre DELORD
        • Sub-Investigator:
          • Marion DESLANDRES
        • Sub-Investigator:
          • Laurence GLADIEFF
        • Sub-Investigator:
          • Eleonora MAIO D'ESPOSITO
        • Sub-Investigator:
          • Delphine LARRIEU-CIRON

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

I1. Male or female patient ≥ 18 years of age.

I2. Histologically or cytologically confirmed diagnosis of metastatic or locally advanced and unresectable solid tumor of any type, except for Nilotinib cohort: only pigmented villonodular synovitis are eligible, not amenable to curative treatment. Concerning primitive tumors of the central nervous system (CNS), all histological types of malignant tumors (including parenchymal and meningeal tumors) are eligible (except for IT).

I3. Documented disease progression at the time of study entry.

I4. At least one prior systemic treatment regimen for locally advanced or metastatic disease - except for Nilotinib cohort : patients can be treated with Nilotinib in first line systemic treatment.

Patients who are candidates for a validated second line treatment regimen are not eligible for the study. For patients with a primitive CNS tumor, the absence of other therapeutic options must be validated by the reference committee for the patient's pathology before inclusion. As there is no prior systemic treatment regimen available for locally advanced or metastatic PEComa, these tumors are eligible for a MTT treatment in first line of their advanced or metastatic disease. No previous treatment by immunotherapy is allowed for IT group.

I5. Patient with measurable disease, defined as at least one lesion that can be accurately measured on CT-scan or MRI according to RECIST 1.1.

I6. A multidisciplinary molecular board must have recommended one of the investigational MTT available in the study after review of a tumor (or blood for pazopanib, olaparib and immunotherapy cohorts) molecular profiling previously established from a biopsied lesion and/or primitive tumor, and/or from a liquid biopsy, respectively (for pazopanib, olaparib and immunotherapy cohorts).

I7. The MTT recommended by the multidisciplinary molecular board after the review of tumor or blood molecular profile is not approved and reimbursed in France for the disease affecting the patient in the same label.

I8. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.

I9. Adequate organ system function as assessed by the following minimal laboratory requirements :

  • Absolute neutrophil count (ANC) ≥ 1 x 109/L (for pazopanib and olaparib: ≥ 1.5 x 109/L)
  • Platelets ≥ 100 x 109/L
  • Hemoglobin ≥ 9 g/dL. Transfusion is not allowed within 7 days of screening assessment. (For olaparib: Hemoglobin ≥ 10 g/dL. Transfusion is not allowed within 28 days of screening assessment, no features suggestive of myelodysplastic syndrome (MDS)/Acute myeloid leukemia (AML) on peripheral blood smear within the 28 days)
  • For pazopanib: activated partial thromboplastin time (aPTT) ≤ 1.2x Upper limit of normal (ULN) and prothrombin time (PT) or international normalized ratio (INR) ≤ 1.2x ULN; Subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation.
  • Aspartate Aminotransferase (AST) and alanine transaminase (ALT) ≤ 3x ULN in the absence of liver metastases (≤ 5x ULN for patients with liver involvement of their cancer) and total bilirubin ≤ 1.5x ULN. (for pazopanib: AST and ALT ≤ 2.5x ULN; concomitant elevations in bilirubin and AST or ALT above 1x ULN are not permitted; for olaparib and IT: AST and ALT ≤ 2.5x ULN in the absence of liver metastases (≤ 5x ULN for patients with liver involvement of their cancer) and total bilirubin ≤ 1.5x ULN.).
  • Serum creatinine ≤ 1.5x ULN or creatinine clearance ≥ 50 mL/min (calculated by Cockcroft-Gault formula, or modification of diet in renal disease (MDRD) formula for patients older than 65 years) (for pazopanib: creatinine clearance ≥ 30 mL/min; for olaparib : creatinine clearance ≥ 51 mL/min; for IT : creatinine clearance ≥ 40 mL/min )
  • For pazopanib: Urine Protein to Creatinine ratio (UPC) <1; if UPC ≥1, 24-hour urine protein must be <1g (use of urine dipstick for renal function assessment is not acceptable).
  • Corrected QT (QTc) interval ≤ 450 msecs (≤ 480 msecs if recommended MTT has no known effect on QT interval) on screening ECG, within 14 days prior to C1D1 (for olaparib : QTc < 470 msec on 2 or more time points within a 24 hour period on screening ECG, within 7 days prior to C1D1).

I10. Life expectancy of at least 4 months.

I11. Specific toxicities related to any prior anti-cancer therapy must have resolved to grade ≤1 (defined by the NCI-CTCAE v4.03) except for alopecia, vitiligo and fatigue. Grade 2 neutropenia or anemia is accepted.

I12. Women of childbearing potential must have a negative pregnancy test performed within 3 days prior to study treatment start. A positive urine test must be confirmed by a serum pregnancy test.

I13. Women of childbearing potential (entering the study after a confirmed menstrual period and who have a negative pregnancy test) and men of reproductive potential must agree, if sexually active, to use two methods of medically acceptable forms of contraception during the study and for at least 8 weeks following the last treatment intake. (for olaparib : during the study and for at least 6 months for women and 3 months for men following the last treatment intake; for IT : during the study and for at least 3 months following the last treatment intake). Refrain from breastfeeding (for nilotinib cohort : not breast-feed for at least two weeks after the last dose of nilotinib) and egg cell donation. Males should not donate sperm during or for 3 months after treatment I14. Signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrollment.

I15. The patient must be affiliated to the French social security system.

I16. The recommended study treatment must have been approved by the medical staff of the Steering committee.

I17. Patient should be able and willing to comply with study visits and procedures as per protocol.

I18. Patient must fulfill ALL following conditions (criteria only applicable for Durvalumab + Tremelimumab cohort):

  • Availability of a pre-treatment sample of primary tumor (only formalin-fixed paraffin-embedded (FFPE) block with sufficient material) and presence of at least one biopsiable tumor lesion for on-treatment biopsy,
  • Weight > 50 Kg,
  • Patient with a maximum of 2 prior lines of treatment at time of C1D1 for their metastatic or locally advanced.

Exclusion Criteria:

Patients eligible for this study must not meet any of the following criteria:

E1. Previous treatment in advanced phase with an investigational therapy inhibiting the same target proteins as this recommended for the study.

E2. Any contra-indication to receive the recommended MTT, including known or suspected hypersensitivity to compounds of similar chemical or biologic composition as the active substance, or to any of the excipients.

E3. For nilotinib, sorafenib, pazopanib, lapatinib and olaparib: Patient with hypokalemia (< Lower Limit of Normal) or known history of congenital long QT syndrome (QT interval prolongation).

E4. Prior malignancy or presence of any other active malignancy. Subjects who have had another malignancy and have been disease-free for 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.

E5. Patient who have had major surgery or trauma within 28 days prior to first dose of investigational product. Patient must have recovered from any effects of any major surgery.

E6. Patient with symptomatic or uncontrolled CNS metastatic involvement of his/her cancer, unless the patient have stable neurological function without evidence of CNS progression within 12 weeks prior to study entry and does not require treatment with enzyme-inducing anticonvulsants or steroids. Patients with a primitive tumor of the CNS are not eligible to IT and if one of the following conditions is fulfilled:

  • Alteration of cognitive functions impeding the patient's comprehension of study and the provision of informed consent by the patient himself/herself.
  • Need for supportive care treatment(s) interfering with study treatment.

E7. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment: radiation therapy (for olaparib : within 3 weeks or 5 half-lives of a drug whichever is longer), surgery or tumor embolization within 14 days prior to the first dose of study treatment OR immunotherapy within 28 days (except for IT : patient already treated with an immunotherapy are excluded) OR chemotherapy (for olaparib : within 3 weeks or 5 half-lives of a drug whichever is longer), biologic therapy, investigational therapy or hormonal therapy within 14 days or 5 half-lives of a drug (whichever is longer). Palliative radiotherapy is authorized only if the irradiated field does not include target lesions.

E8. Administration of any non-oncologic investigational agent within 30 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study treatment.

E9. For oral treatment : Patient with any condition that impairs their ability to swallow and retain tablets and may affect the absorption of the investigational product are excluded.

E10. For pazopanib: Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:

  • Active peptic ulcer disease
  • Known intraluminal metastatic lesion(s) with risk of bleeding
  • Inflammatory bowel disease or other gastrointestinal conditions with increased risk of perforation
  • History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.

E11. For pazopanib and IT: Evidence of active bleeding or bleeding diathesis. E12. For pazopanib: Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage.

  • Lesions infiltrating major pulmonary vessels (contiguous tumour and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating (abutting) the vessels is acceptable.
  • Large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed.
  • Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed.

E13. For pazopanib: Recent hemoptysis.

E14. Any clinically significant and/or uncontrolled medical disease that could compromise the patient's ability to tolerate study treatment or would likely interfere with study procedures or results. These conditions include but are not limited to:

  • Active clinically serious bacterial or fungal infection
  • History of uncontrolled or significant cardiac disease within the past 6 months: left ventricular ejection fraction (LVEF) < 50%, congestive cardiac failure, active ischemic heart disease, ventricular arrhythmia, myocardial infarction within 1 year, unstable angina pectoris, cardiac surgery. (except for Nilotinib, all patients with uncontrolled or significant cardiac disease are excluded)
  • Patients with cerebrovascular accident (including transient ischemic attack), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months are not eligible for pazopanib treatment group
  • Poorly controlled hypertension [for pazopanib: defined as systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg]
  • Severely impaired lung function
  • Active gastrointestinal tract ulceration
  • Acute or chronic uncontrolled liver disease, or severe renal disease
  • Uncontrolled diabetes
  • Known history of human immunodeficiency virus (HIV) infection, or active viral infection (hepatitis B virus (HBV), hepatitis C virus (HCV)) at the time of study entry and/or requiring anti-viral therapy, or chronic hepatitis B or C. Detection of hepatitis C RNA must be performed before inclusion of patients with a history of HCV infection: patients with a positive result are excluded.
  • History of organ allograft or patient taking immunosuppressive treatment.

E15. Patient unable or unwilling to discontinue use of prohibited medications for at least 14 days or 5 half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study.

E16. Pregnant or breastfeeding women. E17. Patients with any medical, psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule or evaluations of the study results.

E18. Patient currently treated with drugs that could interfere with study drugs metabolism E19. Patients filling at least one of these criteria are excluded. (Specific to olaparib)

  • Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
  • Patients considered a poor medical risk due to a serious, uncontrolled seizures, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent myocardial infarction, unstable spinal cord compression , superior vena cava syndrome, extensive bilateral lung disease on High-resolution computed tomography (HRCT) scan.
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation and whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable) are not allowed.
  • Concomitant use of known strong CYP3A inhibitors or moderate CYP3A inhibitors. The required washout period prior to starting olaparib is 2 weeks.
  • Concomitant use of known strong or moderate CYP3A inducers. The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
  • Patients eligible for olaparib (Lynparza®) in its approved indication in France E20. For IT: Patients filling at least one of these criteria are excluded.
  • Patients with lung or urothelial or head and neck cancers or CNS tumors or patients who fulfill conditions to receive one of the investigational therapy of the study
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of Durvalumab or Tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10mg/day of prednisone, or an equivalent corticosteroid.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Arm B:Interruption of targeted treatment

Targeted treatment received during induction period will be discontinued until a first documented off-treatment disease progression occurs. At progression, treatment reintroduction may be proposed to the patient (left at the investigator's appreciation, and upon patient approval).

Treatment may be continued until on-treatment disease progression, unacceptable toxicity or for a maximum of 136 weeks from the date of patient's first study drug intake following inclusion for nilotinib, everolimus, sorafenib, lapatinib, pazopanib, olaparib or until loss of clinical benefit, or until a permanent study drug discontinuation criteria is met for durvalumab + tremelimumab.

If the investigator considers that the treatment cannot be safely reintroduced (regarding patient's condition and/or laboratory results), the patient will be withdrawn from study.
Experimental: Arm A: Maintenance treatment

Patients will continue targeted treatment matching the molecular alterations identified in their tumor

  • for a maximum of 136 weeks starting from the date of patient's first study drug intake following inclusion or a discontinuation criteria (unacceptable toxicity, interruption of study drug more than 28 days, documented on-treatment disease progression, patient decision, investigator decision, pregnancy) is met for nilotinib, everolimus, sorafenib, lapatinib, pazopanib, olaparib.
  • until loss of clinical benefit, or until a permanent study drug discontinuation criteria is met (unacceptable toxicity, interruption of study drug more than 28 days, documented on-treatment disease progression, patient decision, investigator decision, pregnancy) or for up to 2 years duration for patients with CR/PR/SD with the possibility of rechallenge in case of PD after IT cessation for durvalumab + tremelimumab
Drug: Nilotinib (400 mg BID)
Patient with advanced pigmented villonodular synovitis and tumors with mutations of ABL1, KIT, PDGFRA, PDGFRB, DDR1, DDR2, CSF1R, or amplification/translocation of the genes and/or of the ligands.
Other Names:
  • Open cohort
Drug: Everolimus (10 mg QD)
Patients whose tumor harbors mutations or amplification of the PIK3CA, PIK3R1, AKT1, AKT2, mTOR, RICTOR, RAPTOR genes, or with TSC1, TSC2 or PTEN loss (defined as complete loss of both gene copies OR loss of one copy + mutation on the other copy or loss of one copy + loss of expression using immunohistochemistry).
Other Names:
  • Closed cohort
Drug: Sorafenib (400 mg BID)
Patients whose tumor harbors mutations of VEGFR1-3, PDGFRB, FLT3, BRAF (other than V600 mutations), CRAF, HRAS, KRAS or RET or amplification/translocation of the genes and/or of the ligands.
Other Names:
  • Closed cohort
Drug: Lapatinib (1500 mg QD)
Patients whose tumor harbors mutations or amplifications of HER2
Other Names:
  • Closed cohort
Drug: Pazopanib (800 mg QD)
Patients whose tumor harbors mutations of VEGFR1-3, PDGFRA, PDGFRB or KIT* or amplification /translocation of the genes and/or of the ligands.
Other Names:
  • Closed cohort
Combination product: Durvalumab + Tremelimumab
Any molecular types of tumor (which are known to be immunogenic or with high mutation load), except lung, urothelial and head and neck or CNS tumors, or patients who fulfill conditions to receive any other MTT of the MOST Plus study.
Other Names:
  • Open cohort
Drug: Olaparib (300 mg BID)

ATM, BAP1 et BRIP1 Mutation only if double hit documented; BRCA2, BRCA1, RAD51C, PALB2, RAD51D Mutation; BRCA1, BRCA2, ATM and BAP1 Loss; BRCA1, BRCA2, ATM and BAP 1 : mutation and heterozygote deletion. except for patients eligible to olaparib's available labels and reimbursements in France.

NOTE : only prostate cancer with RECIST 1.1 evaluable disease are eligible until the French price and reimbursement

Other Names:
  • Open cohort

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Induction Progression-Free Rate after induction treatment
Time Frame: 12 weeks for MTT or 52 weeks for IT after initiation of study treatment
The proportion of patients without documented disease progression within induction period (the first 12 weeks of study treatment or 52 weeks for IT).
12 weeks for MTT or 52 weeks for IT after initiation of study treatment
Progression-Free Survival (PFS) in both study arms after randomization
Time Frame: 16 weeks after randomisation date
Measured from the date of randomization until the date of event defined as the first documented progression or death from any cause. Patients with no event at the time of the analysis will be censored at the date of the last available tumor assessment.
16 weeks after randomisation date

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Over the induction period
Proportion of patients with complete response (CR) or partial response (PR) as best overall response over the induction period.
Over the induction period
Overall survival (OS)
Time Frame: from the date of randomization to the date of death from any cause
from the date of randomization to the date of death from any cause
Patient's quality of life score (QLQ-C30) in both arms after randomization
Time Frame: At randomization (week 12 for MTT or week 52 for IT), 16 weeks after randomisation (week 28 for MTT or week 68 for IT) and end of study for patient (week 136 for MTT or until up to 130 months after treatment start for IT)
At randomization (week 12 for MTT or week 52 for IT), 16 weeks after randomisation (week 28 for MTT or week 68 for IT) and end of study for patient (week 136 for MTT or until up to 130 months after treatment start for IT)
Safety assessment
Time Frame: Over the whole study
Type, frequency, seriousness and causality of adverse events reported from treatment initiation based on the common toxicity criteria grade (NCI CTC-AE-V4.03)
Over the whole study

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of response (exploratory outcome)
Time Frame: Over the whole study
Measured from the time of first documented response (CR or PR) until the first documented disease progression or death due to underlying cancer, and censored at the date of the last available tumor assessment
Over the whole study
Medico-economic evaluation: cost analysis and cost-effectiveness analysis
Time Frame: From randomization until patient's end of study

Incremental cost-effectiveness ratios (ICERs) will be expressed as:

  • the cost per life year gained;
  • the cost per progression-free year gained.
From randomization until patient's end of study
Progression Free Survival (exploratory outcome)
Time Frame: Through study completion, an average of 1 year
Measured from the date of the first administration of the treatment until the date of event defined as the first documented progression or death from any cause. Patients with no event at the time of the analysis will be censored at the date of the last available tumor assessment.
Through study completion, an average of 1 year
Molecular evolution of tumor at progression (for olaparib and durvalumab + tremelimumab groups)
Time Frame: Through study completion, an average of 1 year
ctDNA analysis
Through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Leon Berard

Collaborators

National Cancer Institute, France

Investigators

  • Principal Investigator: Jean-Yves BLAY, MD, Centre Leon Berard

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2014

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

October 1, 2027

Study Registration Dates

First Submitted

January 6, 2014

First Submitted That Met QC Criteria

January 6, 2014

First Posted (Estimated)

January 7, 2014

Study Record Updates

Last Update Posted (Estimated)

February 13, 2024

Last Update Submitted That Met QC Criteria

February 9, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ET12-081
  • 2012-004510-34 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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