- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04185831
A MolEcularly Guided Anti-Cancer Drug Off-Label Trial (MEGALiT)
October 26, 2020 updated by: Peter Nygren, Uppsala University Hospital
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
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 3 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.
Study Overview
Status
Unknown
Conditions
Intervention / Treatment
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 3 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
Interventional
Enrollment (Anticipated)
154
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
- Name: Hannah Karlsson, PhD
- Phone Number: +46186171654
- Email: hannah.karlsson@akademiska.se
Study Locations
-
-
-
Gothenburg, Sweden
- Recruiting
- Sahlgrenska University Hospital
-
Contact:
- Lars Ny, MD, PhD
- Email: lars.ny@oncology.gu.se
-
Principal Investigator:
- Lars Ny, MD, PhD
-
Lund, Sweden
- Not yet recruiting
- Skåne University Hospital
-
Contact:
- Ana Carneiro, MD, PhD
- Email: ana.carneiro@med.lu.se
-
Principal Investigator:
- Ana Carneiro, MD, PhD
-
Uppsala, Sweden
- Recruiting
- Uppsala University Hospital
-
Contact:
- Joakim Crona, MD, PhD
- Email: joakim.crona@medsci.uu.se
-
Contact:
- Hannah Karlsson, PhD
- Email: hannah.karlsson@akademiska.se
-
Principal Investigator:
- Joakim Crona, MD, PhD
-
-
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
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Adult (age >18 years)
- 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.
- 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.
- ECOG performance status 0-2.
Patients must have acceptable organ function as defined below:
- Absolute neutrophil count ≥ 1.5 x 10^9/L
- Hemoglobin > 90 g/L
- Platelets > 75 x 10^9/L
- Total bilirubin < 2 x ULN
- ASAT (SGOT) and ALAT (SGPT) < 2.5 x institutional ULN (or < 5 x ULN in patients with known hepatic metastases)
- Serum creatinine ≤ 1.5 × ULN or calculated or measured creatinine clearance ≥ 50 mL/min/1.73 m2
- Patients must have objectively measurable disease (by physical or radiographic examination).
- Ability to understand and the willingness to sign a written informed consent document.
- For orally administered drugs, the patient must be able to swallow and tolerate oral medication and must have no known malabsorption syndrome.
- 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.
- Selected tumor types might have disease-specific inclusion criteria, defined by disease-specific study appendix.
Exclusion Criteria:
- Ongoing treatment-related toxicity > grade 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.
- Patients pregnant or nursing.
- Patients of childbearing potential and sexually active and not willing to use highly effective contraceptive.
- 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.
- Some concomitant diseases qualified for exclusion as detailed in main protocol.
- Other serious underlying medical conditions, which, in the Investigator's judgment, could impair the ability of the patient to participate in the trial.
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: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: NF1/MAP2K1
Cobimetinib, 60mg po daily.
28 day cycle; day 1-21 60mg daily, day 22-28 rest period.
|
MEK inhibitor
Other Names:
|
Experimental: MTOR/TSC1/TSC2
Everolimus, 10mg po daily.
|
MTOR inhibitor
Other Names:
|
Experimental: Mutation burden
Atezolizumab.
1200mg iv every 3 weeks.
|
PD-L1 inhibitor
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
1 year follow-up after LPFV
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
1 year follow-up after LPFV
|
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.
|
1 year follow-up after LPFV
|
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.
|
1 year follow-up after LPFV
|
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.
|
1 year follow-up after LPFV
|
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.
|
1 year follow-up after LPFV
|
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
|
1 year follow-up after LPFV
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Peter Nygren, MD, PhD, Uppsala University Hospital
- Study Director: Peter Asplund, BSc, Uppsala University Hospital
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)
October 20, 2020
Primary Completion (Anticipated)
December 1, 2022
Study Completion (Anticipated)
December 1, 2022
Study Registration Dates
First Submitted
November 8, 2019
First Submitted That Met QC Criteria
December 2, 2019
First Posted (Actual)
December 4, 2019
Study Record Updates
Last Update Posted (Actual)
October 28, 2020
Last Update Submitted That Met QC Criteria
October 26, 2020
Last Verified
October 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MEGALiT1901
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
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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