Adapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: My Own Specific Treatment (MOST plus)
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|ClinicalTrials.gov Identifier: NCT02029001|
Recruitment Status : Recruiting
First Posted : January 7, 2014
Last Update Posted : August 31, 2018
|First Submitted Date ICMJE||January 6, 2014|
|First Posted Date ICMJE||January 7, 2014|
|Last Update Posted Date||August 31, 2018|
|Actual Study Start Date ICMJE||March 2014|
|Estimated Primary Completion Date||January 2020 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE
|Change History||Complete list of historical versions of study NCT02029001 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Pre-specified Outcome Measures
|Original Other Pre-specified Outcome Measures||Same as current|
|Brief Title ICMJE||Adapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: My Own Specific Treatment|
|Official Title ICMJE||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 after induction treatment with a selected therapy (Molecular Targeted Therapy (MTT) or 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 this targeted therapy selected based on tumor molecular profile in patients with stable disease.
Each patient enrolled will receive the matching targeted therapy during 12 weeks (MTT) or 24 weeks (IT). At the end of this induction period:
About 80 patients will be treated in each of the 5 MTT treatment groups opened to enrollment and 125 patients will be treated in IT treatment groups , each group corresponding to an available targeted therapy.
|Detailed Description||Not Provided|
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Malignant Solid Neoplasms|
|Study Arms ICMJE||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE
|Original Estimated Enrollment ICMJE||Same as current|
|Estimated Study Completion Date ICMJE||October 2022|
|Estimated Primary Completion Date||January 2020 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
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, 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. 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 molecular profiling previously established from a biopsied lesion and/or primitive tumor.
I7. The MTT recommended by the multidisciplinary molecular board after the review of tumor molecular profile is not approved and reimbursed in France for the disease affecting the patient.
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 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 1 month 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).
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:
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 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:
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:
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)
|Ages ICMJE||18 Years and older (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Listed Location Countries ICMJE||France|
|Removed Location Countries|
|NCT Number ICMJE||NCT02029001|
|Other Study ID Numbers ICMJE||ET12-081
2012-004510-34 ( EudraCT Number )
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Centre Leon Berard|
|Study Sponsor ICMJE||Centre Leon Berard|
|Collaborators ICMJE||National Cancer Institute, France|
|PRS Account||Centre Leon Berard|
|Verification Date||August 2018|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP