Status and phase
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Study type
Funder types
Identifiers
About
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 :
IT cohort :
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.
Enrollment
Sex
Ages
Volunteers
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 :
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):
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:
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:
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.
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:
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)
Primary purpose
Allocation
Interventional model
Masking
900 participants in 2 patient groups
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Central trial contact
Olivier TREDAN, MD; Jean-Yves BLAY, MD
Data sourced from clinicaltrials.gov
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