A MolEcularly Guided Anti-Cancer Drug Off-Label Trial

NCT04185831 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: MEGALiT1901
• Study Type: interventional
• Target: 167
• Locations: 1 country
• Sites: 3

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 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.

Conditions

Solid Tumor

Keywords

mutation status; mutational burden; molecular profiling; precision medicine

Outcome Measures

Primary Outcomes (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

  1 year follow-up after LPFV

Secondary Outcomes (6)

• Additional measurements of treatment efficacy

  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

  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

  1 year follow-up after LPFV

• Genomic analysis

  1 year follow-up after LPFV

• Overall survival

  1 year follow-up after LPFV

Study Arms (4)

NF1/MAP2K1

EXPERIMENTAL

Cobimetinib, 60mg po daily. 28 day cycle; day 1-21 60mg daily, day 22-28 rest period.

Drug: Cobimetinib

MTOR/TSC1/TSC2

EXPERIMENTAL

Everolimus, 10mg po daily.

Drug: Everolimus

Mutation burden

EXPERIMENTAL

Atezolizumab. 1200mg iv every 3 weeks.

Drug: Atezolizumab

PPARi

EXPERIMENTAL

Niraparib. 300mg po daily.

Drug: Niraparib

Interventions

Atezolizumab DRUG

PD-L1 inhibitor

Also known as: Tecentriq

Mutation burden

Everolimus DRUG

MTOR inhibitor

Also known as: Afinitor

MTOR/TSC1/TSC2

Cobimetinib DRUG

MEK inhibitor

Also known as: Cotellic

NF1/MAP2K1

Niraparib DRUG

PARP inhibitor

Also known as: Zejula

PPARi

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Other serious underlying medical conditions, which, in the Investigator's judgment, could impair the ability of the patient to participate in the trial.

Sponsors & Collaborators

• Uppsala University Hospital: lead

Study Sites (3)

Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Skane University Hospital

Lund, Sweden

Location

Uppsala University Hospital

Uppsala, Sweden

Location

MeSH Terms

Interventions

atezolizumab; Everolimus; cobimetinib; niraparib

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Peter Nygren, MD, PhD

  Uppsala University Hospital

  PRINCIPAL INVESTIGATOR

• Peter Asplund, BSc

  Uppsala University Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, professor in oncology

Model Details: Combined umbrella and basket trial. Treatment selection based on mutation status.

Study Record Dates

• First Submitted: November 8, 2019
• First Posted: December 4, 2019
• Study Start: October 20, 2020
• Primary Completion: January 31, 2024
• Study Completion: October 1, 2024
• Last Updated: August 22, 2024

Record last verified: 2024-08

Locations

SE (3)