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A MolEcularly Guided Anti-Cancer Drug Off-Label Trial (MEGALiT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04185831
Recruitment Status : Not yet recruiting
First Posted : December 4, 2019
Last Update Posted : December 4, 2019
Sponsor:
Information provided by (Responsible Party):
Peter Nygren, Uppsala University Hospital

Tracking Information
First Submitted Date  ICMJE November 8, 2019
First Posted Date  ICMJE December 4, 2019
Last Update Posted Date December 4, 2019
Estimated Study Start Date  ICMJE January 2020
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 2, 2019)
Objective Response Rate (ORR) and tumor control rate [Time Frame: From first dose up to 24 months] [ Time Frame: 1 year follow-up after LPFV ]
The proportion of patients that have a best overall response of complete response (CR), partial response (PR) or stable disease ≥16 weeks, as assessed by RECIST 1.1 criteria
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: December 2, 2019)
  • Additional measurements of treatment efficacy [ Time Frame: 1 year follow-up after LPFV ]
    Time to and duration of tumor response and stable disease, progression free survival, overall survival and progression free survival on study drug compared with that on the treatment preceding study drug treatment.
  • Drug-related safety, evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 [ Time Frame: 1 year follow-up after LPFV ]
    Incidence and severity of study drug related adverse events (AEs) and serious adverse events (SAEs). Include recording of changes in laboratory values, vital signs (body temperature, blood pressure, heart rate, respiratory rate), and assessment of physical, dermatological examinations graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
  • Biopsy safety: NCI Common Terminology Criteria for Adverse Events 4.03 as grade 3 - 4 adverse event related to the procedure [ Time Frame: 1 year follow-up after LPFV ]
    Safety of core needle biopsy in advanced cancer scored according to NCI Common Terminology Criteria for Adverse Events 4.03 as grade 3 - 4 adverse event related to the procedure.
  • Genomic analysis [ Time Frame: 1 year follow-up after LPFV ]
    Actionable target concordance between genomic analysis results from the Foundation Medicine platform F1CDx with that from the similar local analysis.
  • Overall survival [ Time Frame: 1 year follow-up after LPFV ]
    Overall survival of patients starting treatment in accordance with 1 of the 4 groups of genomic markers compared with patients included in the trial but that do not start such treatment due to lack of appropriate marker.
  • Feasibility of study design [ Time Frame: 1 year follow-up after LPFV ]
    Feasibility of comprehensive genomic testing of fresh tumor tissue for treatment decision, defined as the proportion of patients included with actionable genomic analysis within 4 weeks from inclusion
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A MolEcularly Guided Anti-Cancer Drug Off-Label Trial
Official Title  ICMJE MEGALiT - a Multicenter, Basket and Umbrella Explorative Trial on the Efficacy and Safety of Molecular Profile Selected Commercially Available Targeted Anti-cancer Drugs in Patients With Advanced Cancers Progressive on Standard Therapy
Brief Summary This is a prospective, open-label, non-randomized combined basket- and umbrella trial divided in two parts; a limited feasibility-oriented part 1 including 154 patients and 4 treatment cohorts and part 2 that will include an expanded cohort of patients and treatment cohorts. The overall aims of the study are to test the feasibility, safety and efficacy of comprehensive genomic profiling on fresh tumor biopsies as a basis for treatment decision making and to compare two different sequencing, bioinformatics and decision-making platforms (part 1). Also to evaluate the efficacy and safety of off-label treatment with cancer drugs in patients selected based on genomic biomarker matching.
Detailed Description This is a prospective, open-label, non-randomized combined basket- and umbrella trial divided in two parts; a limited feasibility-oriented part 1 including 154 patients and 4 treatment cohorts (mutation/drug) and part 2 that will include an expanded cohort of patients and treatment cohorts. The overall aims of the study are to test the feasibility, safety and efficacy of comprehensive genomic profiling on fresh tumor biopsies as a basis for treatment decision making and to compare two different sequencing, bioinformatics and decision-making platforms (part 1). Also to evaluate the efficacy and safety of off-label treatment with cancer drugs in patients selected based on genomic biomarker matching.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Combined umbrella and basket trial. Treatment selection based on mutation status.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor
Intervention  ICMJE
  • Drug: Atezolizumab
    PD-L1 inhibitor
    Other Name: Tecentriq
  • Drug: Everolimus
    MTOR inhibitor
    Other Name: Afinitor
  • Drug: Niraparib
    PARP inhibitor
    Other Name: Zejula
  • Drug: Cobimetinib
    MEK inhibitor
    Other Name: Cotellic
Study Arms  ICMJE
  • Experimental: ATM/BRCA1/BRCA2
    Niraparib, 300mg po twice daily.
    Intervention: Drug: Niraparib
  • Experimental: NF1/MAP2K1
    Cobimetinib, 60mg po daily. 28 day cycle; day 1-21 60mg daily, day 22-28 rest period.
    Intervention: Drug: Cobimetinib
  • Experimental: MTOR/TSC1/TSC2
    Everolimus, 10mg po daily.
    Intervention: Drug: Everolimus
  • Experimental: Mutation burden
    Atezolizumab. 1200mg iv every 3 weeks.
    Intervention: Drug: Atezolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: December 2, 2019)
154
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Adult (age >18 years)
  2. Patients with histologically-proven, locally advanced or metastatic solid tumor (part 1; hematological malignancies also eligible in part 2) progressive while on last line established therapy considered available for the patient. For re-recruitment (part 2) patients must be progressive while on trial defined treatment or off-protocol treatment.
  3. Fresh tumor sampling by biopsy must be possible, except for patients with CNS malignancy who can be included based on molecular analysis of archived tumor material.
  4. ECOG performance status 0-2.
  5. Patients must have acceptable organ function as defined below:

    1. Absolute neutrophil count ≥ 1.5 x 10^9/L
    2. Hemoglobin > 90 g/L
    3. Platelets > 75 x 10^9/L
    4. Total bilirubin < 2 x ULN
    5. ASAT (SGOT) and ALAT (SGPT) < 2.5 x institutional ULN (or < 5 x ULN in patients with known hepatic metastases)
    6. Serum creatinine ≤ 1.5 × ULN or calculated or measured creatinine clearance ≥ 50 mL/min/1.73 m2
  6. Patients must have objectively measurable disease (by physical or radiographic examination).
  7. Ability to understand and the willingness to sign a written informed consent document.
  8. For orally administered drugs, the patient must be able to swallow and tolerate oral medication and must have no known malabsorption syndrome.
  9. Negative pregnancy test in women of childbearing potential (premenopausal or <12 months of amenorrhea post-menopause and who have not undergone surgical sterilization). Women of childbearing potential must use highly effective method of contraception, i.e. combined hormonal contraception, or progestogen-only hormonal contraception, or intrauterine device, or intrauterine hormone-releasing system, or bilateral tubal occlusion, or vasectomized partner, or sexual abstinence for the duration of participation in the study, and four months following completion of study therapy.
  10. Selected tumor types might have disease-specific inclusion criteria, defined by disease-specific study appendix.

Exclusion Criteria:

  1. Ongoing treatment-related toxicity > grade 2.
  2. Patients receiving any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) except for medications that are prescribed for supportive care but may potentially have an anti-cancer effect (e.g., megestrol acetate, bisphosphonates, somatostatin analogues and prednisone, or equivalent, >5 mg/d). These medications must have been started ≥ 1 week prior to the screening visit on this study. Radiotherapy to non-target lesions is allowed.
  3. Patients pregnant or nursing.
  4. Patients of childbearing potential and sexually active and not willing to use highly effective contraceptive.
  5. Patients with known active progressive CNS metastases. Patients with previously treated CNS metastases are eligible, provided that the patient has not experienced a seizure or had a clinically significant change in neurological status within the 3 months prior to inclusion. All patients with previously treated CNS metastases must be stable for at least 1 month after completion of treatment and off steroid treatment prior to inclusion.
  6. Some concomitant diseases qualified for exclusion as detailed in main protocol.
  7. Other serious underlying medical conditions, which, in the Investigator's judgment, could impair the ability of the patient to participate in the trial.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Hannah Karlsson, PhD +46186171654 hannah.karlsson@akademiska.se
Listed Location Countries  ICMJE Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04185831
Other Study ID Numbers  ICMJE MEGALiT1901
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Peter Nygren, Uppsala University Hospital
Study Sponsor  ICMJE Uppsala University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Peter Nygren, MD, PhD Uppsala University Hospital
Study Director: Peter Asplund, BSc Uppsala University Hospital
PRS Account Uppsala University Hospital
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP