Clinical Trials /

A MolEcularly Guided Anti-Cancer Drug Off-Label Trial

NCT04185831

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 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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A MolEcularly Guided Anti-Cancer Drug Off-Label Trial
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: MEGALiT1901
  • NCT ID: NCT04185831

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
AtezolizumabTecentriqMutation burden
EverolimusAfinitorMTOR/TSC1/TSC2
NiraparibZejulaATM/BRCA1/BRCA2
CobimetinibCotellicNF1/MAP2K1

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
ATM/BRCA1/BRCA2ExperimentalNiraparib, 300mg po twice daily.
  • Niraparib
NF1/MAP2K1ExperimentalCobimetinib, 60mg po daily. 28 day cycle; day 1-21 60mg daily, day 22-28 rest period.
  • Cobimetinib
MTOR/TSC1/TSC2ExperimentalEverolimus, 10mg po daily.
  • Everolimus
Mutation burdenExperimentalAtezolizumab. 1200mg iv every 3 weeks.
  • Atezolizumab

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Additional measurements of treatment efficacy
Time Frame:1 year follow-up after LPFV
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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 Issue:
Description: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.
Measure:Genomic analysis
Time Frame:1 year follow-up after LPFV
Safety Issue:
Description:Actionable target concordance between genomic analysis results from the Foundation Medicine platform F1CDx with that from the similar local analysis.
Measure:Overall survival
Time Frame:1 year follow-up after LPFV
Safety Issue:
Description: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.
Measure:Feasibility of study design
Time Frame:1 year follow-up after LPFV
Safety Issue:
Description: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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Uppsala University Hospital

Trial Keywords

  • mutation status
  • mutational burden
  • molecular profiling
  • precision medicine

Last Updated

December 2, 2019