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Solid TumorPhase 2MEGALiTNCT04185831

A MolEcularly Guided Anti-Cancer Drug Off-Label Trial

A Phase 2 study testing Atezolizumab, Everolimus and Cobimetinib in people with Solid Tumor, run by Uppsala University Hospital at 3 sites in Sweden.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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 3 treatment cohorts and part 2 that will include an expanded cohort of patients and treatment cohorts. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor
What is being tested?
Atezolizumab, Everolimus and Cobimetinib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
167 participants
Where
3 sitesSweden
Study dates
20 Oct 2020to Oct 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 16Show fewer
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

3 sites in 1 country.

Sweden3 sites

  • Sahlgrenska University Hospital

    Gothenburg

  • Skane University Hospital

    Lund

  • Uppsala University Hospital

    Uppsala

Other trials in Sweden

About this study

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

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.

Read the 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.

Conditions
Solid Tumor
Being tested
Atezolizumab, Everolimus, Cobimetinib, Niraparib
Keywords
mutation status, mutational burden, molecular profiling, precision medicine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Also called Tecentriq

    PD-L1 inhibitor

  • EverolimusDrug

    Also called Afinitor

    MTOR inhibitor

  • CobimetinibDrug

    Also called Cotellic

    MEK inhibitor

  • NiraparibDrug

    Also called Zejula

    PARP inhibitor

Study groups in NCT04185831
Study groupRoleWhat they receive
NF1/MAP2K1ExperimentalCobimetinib, 60mg po daily. 28 day cycle; day 1-21 60mg daily, day 22-28 rest period.
Receives: Drug: Cobimetinib
MTOR/TSC1/TSC2ExperimentalEverolimus, 10mg po daily.
Receives: Drug: Everolimus
Mutation burdenExperimentalAtezolizumab. 1200mg iv every 3 weeks.
Receives: Drug: Atezolizumab
PPARiExperimentalNiraparib. 300mg po daily.
Receives: Drug: Niraparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR) and tumor control rate [Time Frame: From first dose up to 24 months]

    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

    Measured: 1 year follow-up after LPFV

Secondary outcomes (6)

  1. Additional measurements of treatment efficacy

    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.

    Measured: 1 year follow-up after LPFV

  2. Drug-related safety, evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03

    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.

    Measured: 1 year follow-up after LPFV

  3. Biopsy safety: NCI Common Terminology Criteria for Adverse Events 4.03 as grade 3 - 4 adverse event related to the procedure

    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.

    Measured: 1 year follow-up after LPFV

  4. Genomic analysis

    Actionable target concordance between genomic analysis results from the Foundation Medicine platform F1CDx with that from the similar local analysis.

    Measured: 1 year follow-up after LPFV

  5. Overall survival

    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.

    Measured: 1 year follow-up after LPFV

  6. Feasibility of study design

    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

    Measured: 1 year follow-up after LPFV

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Dec 2019
  2. Study start20 Oct 2020
  3. Primary completion31 Jan 2024
  4. Study completionOct 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Combined umbrella and basket trial. Treatment selection based on mutation status.
Masking
None (open label)
Enrolment
167 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04185831
Sponsor's protocol ID
MEGALiT1901
Acronym
MEGALiT
Status last verified
Aug 2024
First submitted
8 Nov 2019
Last updated
22 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atezolizumab, Everolimus and Cobimetinib in people with Solid Tumor, run by Uppsala University Hospital at 3 sites in Sweden.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 22 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04185831.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2024.

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