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 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.
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
Interventions
Drug | Synonyms | Arms |
---|
Atezolizumab | Tecentriq | Mutation burden |
Everolimus | Afinitor | MTOR/TSC1/TSC2 |
Cobimetinib | Cotellic | NF1/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 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.
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.
Trial Arms
Name | Type | Description | Interventions |
---|
NF1/MAP2K1 | Experimental | Cobimetinib, 60mg po daily. 28 day cycle; day 1-21 60mg daily, day 22-28 rest period. | |
MTOR/TSC1/TSC2 | Experimental | Everolimus, 10mg po daily. | |
Mutation burden | Experimental | Atezolizumab. 1200mg iv every 3 weeks. | |
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: | Recruiting |
Lead Sponsor: | Uppsala University Hospital |
Trial Keywords
- mutation status
- mutational burden
- molecular profiling
- precision medicine
Last Updated
October 28, 2020