A Randomised Phase II Study of Roginolisib in Patients with Advanced/metastatic Uveal Melanoma

Study Purpose

The goal of this clinical trial is to learn how roginolisib works in comparison to standard treatment in adult patients with uveal/ocular melanoma. The main questions it aims to answer are: Does roginolisib extend overall survival compared to standard treatment? How does dosing of roginolisib impact quality of life compared to standard treatment?

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Male or female aged 18 years or older; 2. Histologically or cytologically proven diagnosis of advanced or metastatic UM or ocular melanoma (arising from ocular melanocytes regardless of intraocular location) 3. Patients who have progressed following at least 1 prior immunotherapy treatment for advanced or metastatic UM. For patients who are HLA-A*02:01 positive prior treatment should have included tebentafusp, if available or patients clinically suitable. Patients who have also received prior melphalan hepatic infusion may be included; 4. Presence of at least one lesion suitable for biopsy. Biopsies will be mandatory at Screening and C5D1 (see Sections 8.1.3 and 8.6 for more information); 5. Presence of at least one measurable lesion as per RECIST v1.1. Any lesion that is biopsied cannot be used as a measurable lesion for the purposes of RECIST v1.1 assessments; 6. ECOG performance status of 0 to 1; 7. Male or female patients of child-bearing potential must be willing to use highly effective forms of contraception (refer to APPENDIX 7 for details on highly effective methods of contraception and definitions of women of childbearing potential and of fertile men) 8. All other relevant medical conditions must be well managed and stable, in the Investigator's opinion, for at least 28 days prior to first dose of roginolisib; 9. Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses.

Exclusion Criteria:

1. Inability to swallow oral medication; 2. a). History of a prior Grade 3 or 4 irAE or any grade ocular irAE from prior immunotherapy which did not respond to corticosteroid therapy or resolved with treatment interruptions and returned to at least Grade 1; b). Have not recovered from toxic effect(s) of prior therapy to ≤ Grade 1, other than alopecia or fatigue or neuropathy which must be ≤ Grade 1; 3. Presence of symptomatic or untreated CNS metastases or CNS metastases that require doses of corticosteroids within the prior 3 weeks to first dose of roginolisib. Patients with brain metastases are eligible if lesions have been treated with localised therapy and there is no evidence of progressive disease for at least 4 weeks prior to the first dose of IMP; 4. Abnormal liver enzymes defined as: 1. ALT or AST ≥ 3× upper limit of normal (ULN) (≥ 5× ULN in patients with liver metastases); 2. Total bilirubin ≥ 1.5 × ULN are excluded unless direct bilirubin is ≤ ULN. If there is no institutional ULN, then direct bilirubin must be < 40% of total bilirubin to be eligible (except patients with Gilbert syndrome); 5. Any other clinically significant out of range laboratory values; 6. Clinically significant cardiac disease or impaired cardiac function which may limit the patient´s participation in the clinical study. These may include unstable angina (i.e., not responsive to medical intervention), myocardial infarct in last 6 months, QTcF prolongation of more than 500 ms; 7. Evidence of interstitial lung disease or active, non-infectious pneumonitis, pulmonary fibrosis; 8. Active infection requiring systemic antibiotic therapy. Patients requiring systemic antibiotics for infection must have completed therapy at least 1 week prior to the first dose of IMP; 9. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional protocol; 10. Malignant disease, other than that being treated in this study (e.g., skin/cutaneous and/or mucosal melanoma). Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to first dose of IMP; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type; 11. Any medical condition that would, in the Investigator's or Sponsor's judgment, prevent the patient's participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results; 12. Treatment with anti-tumour medications or investigational drugs within 14 days or 5 half-lives (whichever is longer) of administration of first dose of IMP; 13. Major surgery within 2 weeks of the first dose of IMP (minimally invasive procedures such as bronchoscopy, tumour biopsy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery and are not exclusionary); 14. Radiotherapy within 4 weeks of the first dose of IMP, with the exception of palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumour mass; 15. Pregnant, likely to become pregnant, or lactating women.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT06717126
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

iOnctura
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Michael Lahn, MD
Principal Investigator Affiliation iOnctura
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries Italy, Spain, United Kingdom
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Uveal Melanoma, Ocular Melanoma
Additional Details

A Phase II open-label, randomised, parallel-arm study, which will assess the clinical efficacy of oral roginolisib (IOA 244 [roginolisib hemi-fumarate]) as monotherapy against a control of Investigator´s treatment choice in patients with advanced or metastatic uveal melanoma (UM). This study will enrol approximately 85 male and female patients aged over 18 years with advanced or metastatic UM, who have progressed following at least 1 prior immunotherapy treatment. The disease must be measurable (i.e., at least 1 measurable lesion) as per RECIST v1.1 by Computerised Tomography (CT) scan or Magnetic Resonance Imaging (MRI).

Arms & Interventions

Arms

Experimental: Arm 1 - Roginolisib 80mg

IOA-244: 80 mg (corresponding to 72 mg roginolisib) daily

Active Comparator: Arm 2 - Investigator choice of standard of care

Investigator´s choice of therapy

Experimental: Arm 3 - Roginolisib 40mg

IOA-244: 40 mg (corresponding to 36 mg roginolisib) daily

Interventions

Drug: - roginolisib

rognolisib

Drug: - Investigator choice of standard therapy

Investigator will choose the most appropriate treatment standardly given to patients

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Bari, Italy

Status

Not yet recruiting

Address

SSD Tumori Rari e Melanoma Viale Orazio Flacco

Bari, , 70124

Site Contact

Michele Guida, Dr

[email protected]

+39 0805555136

Napoli, Italy

Status

Not yet recruiting

Address

IRCSS National Cancer Institute, "G.Pascale" Foundation Dip. CORP-S di Ricerca ed Assistenziale Cute, Melanoma lmmunologia Oncologica Sperimentale e Terapie Innovative

Napoli, , 80131

Site Contact

Paolo A Ascierto, Dr

[email protected]

39 08117770443

Padova, Italy

Status

Not yet recruiting

Address

IRCSS Istituto Oncologico Veneto UOS Oncologia 2 del Melanoma Ospedale Busonera

Padova, , 35128

Site Contact

Jacopo Pigozzo, Dr

[email protected]

39 0498215938

IRCCS Istituto Clinico Humanitas, Rozzano, Italy

Status

Not yet recruiting

Address

IRCCS Istituto Clinico Humanitas

Rozzano, , 20089

Site Contact

Armando Santoro, Prof

[email protected]

39 02 82244080

A.O.U.S. Santa Maria delle Scotte, Sienna, Italy

Status

Not yet recruiting

Address

A.O.U.S. Santa Maria delle Scotte

Sienna, , 53100

Site Contact

Michele Maio, Prof

[email protected]

+390577586335

Barcelona, Spain

Status

Not yet recruiting

Address

Institut Catala d'Oncologia - ICO L'Hospitalet

Barcelona, , 08908

Site Contact

Josep Piulats, Dr Josep M Piulats

[email protected]

+34932607744

Hospital Universitario La Paz, Madrid, Spain

Status

Not yet recruiting

Address

Hospital Universitario La Paz

Madrid, , 28046

Site Contact

Enrique Espinosa, Dr

[email protected]

+34917277516

Santiago de Compostela, Spain

Status

Not yet recruiting

Address

Complejo Hospitalario Universitario de Santiago - CHUS

Santiago de Compostela, , 15706

Site Contact

Teresa Curiel, Dr Teresa Curiel

[email protected]

+34663609134

Seville, Spain

Status

Not yet recruiting

Address

Hospital Universitario Virgen Macarena, University of Seville

Seville, ,

Site Contact

Maria del Carmen Álamo de la Gala, Dr Álamo de la Gala

[email protected]

+34629310196

Valencia, Spain

Status

Not yet recruiting

Address

Consorcio Hospital General Universitario de València - CHGUV

Valencia, , 46014

Site Contact

Alfonso Berrocal-Jaime, Dr Alfonso Berrocal-Jaime

[email protected]

+34963131800 #437635

Northwood, Middlesex, United Kingdom

Status

Recruiting

Address

East and North Hertfordshire NHS Trust (Mount Vernon Cancer Centre)

Northwood, Middlesex, HA6 2RN

Site Contact

Paul Nathan, Prof Paul Nathan

[email protected]

02038262535

Bebington, Wirral, United Kingdom

Status

Not yet recruiting

Address

The Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, Wirral, CH63 4JH

Site Contact

Joseph Sacco, Dr Joseph Sacco

[email protected]

0151 556 5000

Glasgow, United Kingdom

Status

Recruiting

Address

Beatson West of Scotland Cancer Centre, Glasgow (NHS Greater Glasgow & Clyde)

Glasgow, , G12 0YN

Site Contact

Prof Jeff Evans

[email protected]

0141 301 7073

University College London Hospital NHS, London, United Kingdom

Status

Not yet recruiting

Address

University College London Hospital NHS

London, , NW1 2PG

Site Contact

Heather Shaw, Dr Heather Shaw

[email protected]

020 3447 2929 #72930

Royal Marsden Hospital, London, United Kingdom

Status

Not yet recruiting

Address

Royal Marsden Hospital

London, , SW3 6JJ

Site Contact

James Larkin, Prof James Larkin

[email protected]

0207 811 8576

Southampton, United Kingdom

Status

Recruiting

Address

University Hospital Southampton NHS Foundation

Southampton, , SO16 6YD

Site Contact

Matthew Wheater, Dr Matthew Wheater

[email protected]

02381208639

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