A Study of ART0380 for the Treatment of Advanced or Metastatic Solid Tumors

NCT04657068 | Recruiting Phase 1 FDA Drug

• 1 other identifier: ART0380C001
• Study Type: interventional
• Target: 442
• Locations: 4 countries
• Sites: 79

Brief Summary

This clinical trial is evaluating a drug called ART0380 in participants with advanced or metastatic solid tumors. The main goals of this study are to:

• Find the recommended dose of ART0380 that can be given safely to participants alone and in combination with gemcitabine or irinotecan
• Learn more about the side effects of ART0380 alone and in combination with gemcitabine or irinotecan
• Learn more about the effectiveness of ART0380 alone and in combination with gemcitabine or irinotecan

Conditions

Advanced Cancer; Metastatic Cancer; Ovarian Cancer; Primary Peritoneal Cancer; Fallopian Tube Cancer; Endometrial Cancer; Metastatic Colorectal Cancer; Pancreatic Ductal Adenocarcinoma; Acinar Cell Carcinoma

Keywords

Loss of Ataxia Telangiectasia Mutated (ATM) protein

Outcome Measures

Primary Outcomes (4)

• Part A: Maximum tolerated dose (MTD) by the number of participants with dose limiting toxicities (DLTs) from ART0380 monotherapy and in combination with gemcitabine or irinotecan

  From Cycle 0 Day -2 to Cycle 1 Day 21. Each cycle is 21 days.

• Parts B1/B3/B4: Number of participants with adverse events following administration of ART0380 monotherapy and/or in combination with irinotecan at RP2Ds.

  Safety reported as incidence of adverse events

  From Cycle 1 Day 1 until up to 30 days after the last dose of ART0380. Each cycle is 21 days.

• Part B2: Progression free survival by RECIST 1.1 in participants receiving ART0380 in combination with gemcitabine or gemcitabine alone

  Progression free survival (PFS)

  Every 6 weeks from Cycle 1 Day 1 for 18 weeks, then every 9 weeks up to approximately 24 months. Each cycle is 21 days.

• Parts B5/B6: Object Response Rate (ORR) based on RECIST 1.1 to access anti-tumor activity of ART0380 in combination with irinotecan in each cohort.

  Objective Response Rate (ORR)

  Every 6 weeks from Cycle 1 Day 1, until disease progression or death or start of a new anti-cancer therapy, up to 2 years. Each Cycle is 21 days.

Secondary Outcomes (33)

• Part B2: Number of participants with adverse events following administration of ART0380 in combination with gemcitabine or gemcitabine alone

  From Cycle 1 Day 1 until up to 30 days after the last dose of ART0380 or gemcitabine. Each cycle is 21 days.

• Part B5/B6: Number of participants with adverse events following administration of ART0380 at the RP2D in combination with irinotecan.

  From Cycle 1 Day 1 until up to 30 days after the last dose of ART0380 or irinotecan. Each cycle is 21 days.

• Pharmacokinetic Analysis (single dose): determine the plasma concentration of ART0380 when given alone and in combination

  PK will be measured at each cycle from Cycle 0 to Cycle 4. Each cycle is 21 days.

• Pharmacokinetic Analysis (multiple dose): determine the plasma concentration of ART0380 when given alone and in combination

  PK will be measured at each cycle from Cycle 0 to Cycle 4. Each cycle is 21 days.

• Pharmacokinetic Analysis (single and multiple dose): Renal clearance of ART0380

  Urine PK will be measured during Cycle 1. Cycle 1 is 21 days.

Study Arms (10)

Part A1

EXPERIMENTAL

Part A1 evaluated intermittent and continuous dosing of ART0380 monotherapy. Treatment was given in 21-day cycles.

Drug: ART0380

Part A2

EXPERIMENTAL

Part A2 evaluated intermittent dosing of ART0380 in combination with gemcitabine in 21-day cycles.

Drug: ART0380; Drug: Gemcitabine

Part A3

EXPERIMENTAL

Part A3 evaluated intermittent dosing of ART0380 in combination with irinotecan in 21-day cycles.

Drug: ART0380; Drug: Irinotecan

Part B1

EXPERIMENTAL

In Part B1, up to 7 cohorts enrolled participants with solid cancers with alterations in the ATM (ataxia-telangiectasia mutated) gene likely to predict for loss of ATM protein will be treated with either * ART0380 monotherapy Or * ART0380 in combination with irinotecan

Drug: ART0380; Drug: Irinotecan

Part B2

EXPERIMENTAL

In Part B2, participants with high grade serous ovarian, primary peritoneal, or fallopian tube carcinoma were randomized (open label) 1:1 to either ART0380 in combination with gemcitabine or gemcitabine alone.

Drug: ART0380; Drug: Gemcitabine

Part B3

EXPERIMENTAL

in Part B3, participants with persistent or recurrent endometrial cancer (EC) received ART0380 monotherapy on either a continuous daily dose or on an intermittent schedule for a 21-day cycle.

Drug: ART0380

Part B4

EXPERIMENTAL

In Part B4, participants with advanced or metastatic solid tumors received ART0380 monotherapy on either a continuous daily dose or on an intermittent schedule for a 21-day cycle.

Drug: ART0380

Part B5

EXPERIMENTAL

In Part B5, participants with colorectal cancer (CRC) will receive ART0380 in combination with irinotecan on a 21-day cycle.

Drug: ART0380; Drug: Irinotecan

Part B6

EXPERIMENTAL

In Part B6, participants with pancreatic ductal adenocarcinoma (PDAC) or acinar cell carcinoma will receive ART0380 in combination with irinotecan on a 21-day cycle.

Drug: ART0380; Drug: Irinotecan

Part A3 Fed/Fast

EXPERIMENTAL

Part A3 Fed/Fast will evaluate intermittent dosing of ART0380 in combination with irinotecan in 21-day cycles in a fasting or fed state.

Drug: ART0380; Drug: Irinotecan

Interventions

ART0380 DRUG

Participants will receive ART0380 by mouth either intermittently (either once daily 3 days on, 4 days off; days 2-4 and 9-11;or days 1-3 and 8-10) or continuously (once daily each day) in 21 day cycles.

Part A1; Part A2; Part A3; Part A3 Fed/Fast; Part B1; Part B2; Part B3; Part B4; Part B5; Part B6

Gemcitabine DRUG

Gemcitabine will be administered on Days 1 and 8 of a 21-day cycle.

Also known as: Gemzar

Part A2; Part B2

Irinotecan DRUG

Irinotecan will be administered as a 90-minute infusion on Days 1 and 8 of a 21 day cycle.

Also known as: Camptosar, Camptothecin-11

Part A3; Part A3 Fed/Fast; Part B1; Part B5; Part B6

Eligibility Criteria

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

You may qualify if:

• Signed informed consent
• Discontinued all previous treatments for cancer for at least 21 days or 5 half-lives, whichever is shorter, and recovered from the acute effects of therapy to CTCAE Grade ≤1. Palliative radiotherapy must have completed 1 week prior to start of study treatment.
• If patients have a known germline BRCA mutation or a cancer with a somatic BRCA mutations or which is HRD positive and for which there is an approved PARP inhibitor, participants should have received such treatment before participating in the study unless contra-indicated
• At least 1 radiologically evaluable lesion (measurable and/or non-measurable) that can be assessed at baseline and is suitable for repeated radiological evaluation by RECIST v1.1 or Prostate Cancer Working Group-3 Guidelines (PCWG-3)
• Acceptable hematologic, renal, hepatic, and coagulation functions independent of transfusions and granulocyte colony-stimulating factor
• Non-irradiated tumor tissue sample (archival or newly obtained core biopsy of a tumor lesion) available for submission for analysis.
• Female patients of childbearing potential and male patients with female partners of childbearing potential are required to use highly effective contraception plus one barrier method during their participation in the study and for 7 months and 5 months respectively following the last dose. For male and female patients given gemcitabine or irinotecan, highly effective contraception plus one barrier method must be used from study entry until 6 months after the last dose of study treatment. Male patients are required to refrain from donating sperm and female patients are required to refrain from donating eggs, during their participation in the study and for 6 months following last dose.
• Estimated life expectancy of ≥12 weeks
• Reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
• Performance status of 0-1 on the ECOG Scale
• Advanced or metastatic cancer which is refractory to standard therapies, or for which no standard therapies exist, or for which the investigator feels no other active therapy is required for the duration of the study
• Performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale
• Advanced or metastatic cancer for which gemcitabine is an appropriate treatment. Prior treatment with gemcitabine is permitted.
• Advanced or metastatic cancer for which irinotecan is an appropriate treatment. Prior treatment with irinotecan is permitted.
• For food effect cohort only: Patients must be able to eat a high-fat meal within a 30 minute period, as provided by the study site.

You may not qualify if:

• Women who are pregnant, breast feeding, or who plan to become pregnant while in the study or within 7 months after the last administration of study treatment
• Men who plan to father a child while in the study or within5 months after the last administration of study treatment
• Serious concomitant systemic disorder that would compromise the participants ability to adhere to the protocol including: one or more opportunistic HIV/AIDs-related infections within the past 12 months, a known hepatitis B virus, or known hepatitis C virus; documented active or chronic tuberculosis infection; malignancy prior to the one currently being treated that is not in remission
• Have ongoing interstitial lung disease or pneumonitis (whether symptomatic or asymptomatic).
• Moderate or severe cardiovascular disease
• Valvulopathy that is severe, moderate, or deemed clinically significant
• Documented major electrocardiogram (ECG) abnormalities which are clinically significant
• Symptomatic or uncontrolled brain metastases, spinal cord compression, or leptomeningeal disease requiring concurrent treatment
• Received a live vaccine within 30 days before the first dose of study treatment
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate
• Recent major surgery within 4 weeks prior to entry into the study or minor surgery within 1 week of entry into the study
• Drainage for ascites, pleural effusion or pericardial fluid within 4 weeks before the first dose of study treatment.
• A significant bleeding disorder or vasculitis or had a Grade ≥3 bleeding episode within 12 weeks prior to enrollment
• Currently enrolled in a clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study
• Patients who have symptoms or signs of clinically unacceptable deterioration of the primary disease at the time of screening.

Sponsors & Collaborators

• Artios Pharma Ltd: lead

Study Sites (79)

University of Alabama at Birmingham

Birmingham, Alabama, 35294-3300, United States

RECRUITING

Mayo Clinic (Arizona)

Scottsdale, Arizona, 85259, United States

RECRUITING

University of Arkansas - Winthrop P. Rockefeller Cancer Institute

Little Rock, Arkansas, 72205, United States

RECRUITING

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

Sansum Clinic

Santa Barbara, California, 93105, United States

RECRUITING

Providence Medical Foundation

Santa Rosa, California, 95403, United States

RECRUITING

Rocky Mountain Cancer Center

Denver, Colorado, 80218, United States

RECRUITING

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

RECRUITING

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

RECRUITING

Mayo Clinic (Florida)

Jacksonville, Florida, 32224, United States

RECRUITING

Cancer Specialists of North Florida

Jacksonville, Florida, 32256, United States

RECRUITING

Florida Cancer Specialists

Orlando, Florida, 32827, United States

COMPLETED

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

RECRUITING

Florida Cancer Specialists

West Palm Beach, Florida, 33401, United States

RECRUITING

Hope and Healing Cancer Services

Hinsdale, Illinois, 60521, United States

RECRUITING

Community Health Network

Indianapolis, Indiana, 46250, United States

RECRUITING

Our Lady of the Lake

Baton Rouge, Louisiana, 70808, United States

RECRUITING

Maryland Oncology Hematology - Primary

Columbia, Maryland, 21044, United States

RECRUITING

Minnesota Oncology Hematology

Maple Grove, Minnesota, 55369, United States

RECRUITING

Mayo Clinic (Minnesota)

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

Hematology Oncology Associates of Central New York

East Syracuse, New York, 13057, United States

RECRUITING

Northwell Health Cancer Institute

Lake Success, New York, 11042, United States

RECRUITING

Oncology Hematology Care Primary

Cincinnati, Ohio, 45242, United States

RECRUITING

Taylor Cancer Research Center

Maumee, Ohio, 43537, United States

RECRUITING

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

University of Pennsylvania / Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Tennessee Oncology, PLLC

Chattanooga, Tennessee, 37404, United States

RECRUITING

Baptist Cancer Center

Memphis, Tennessee, 38120, United States

COMPLETED

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

Texas Oncology - Central/South Texas

Austin, Texas, 78705, United States

RECRUITING

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

RECRUITING

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

RECRUITING

Texas Oncology - Northeast Texas

Flower Mound, Texas, 75028, United States

RECRUITING

Oncology Consultants

Houston, Texas, 77030, United States

COMPLETED

Texas Oncology - San Antonio

San Antonio, Texas, 78240, United States

RECRUITING

Utah Cancer Specialists

Salt Lake City, Utah, 84106, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Institut Gustave Roussy

Villejuif, Cedex, 94805, France

RECRUITING

Institut Bergonie

Bordeau, 33076, France

RECRUITING

Marseille University Hospital Timone

Marseille, 13005, France

RECRUITING

Saint-Louis Hospital

Paris, 75010, France

RECRUITING

Hospital de la Pitié-Salpêtrière

Paris, 75013, France

RECRUITING

Hospital General Universitario de Elche

Elche, Alicante, 03203, Spain

RECRUITING

H. Parc Tauli

Sabadell, Barcelona, 08208, Spain

RECRUITING

Next Oncology Barcelona, IOB

Barcelona, Catalonia, 08023, Spain

RECRUITING

Hospital Arnau de Vilanova

Lleida, Catalonia, 25198, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

RECRUITING

Next - Hospital Quironsalud Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

RECRUITING

Hospital Clínico Universitario Virgen de la Arrixaca

El Palmar, Murcia, 30120, Spain

RECRUITING

Clínica Universidad de Navarra

Madrid, Planta -2, 28027, Spain

RECRUITING

Hospital Clínico Universitario de Santiago (CHUS)

A Coruña, 00000, Spain

RECRUITING

Hospital Teresa Herrera (CHUAC)

A Coruña, 15006, Spain

RECRUITING

Institut Català d'Oncologia Badalona - Hospital Germans Trias i Pujol

Badalona, 08916, Spain

RECRUITING

Vall d'Hebron Institute of Oncology (VIHO)

Barcelona, 08035, Spain

RECRUITING

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

RECRUITING

ICO Hospitalet

Barcelona, 08903, Spain

RECRUITING

Hospital Universitario Reina Sofia de Córdoba

Córdoba, 14004, Spain

RECRUITING

Hospital Universitari Doctor Josep Trueta- ICO de Girona

Girona, 17007, Spain

RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

RECRUITING

MD Anderson Cancer Center (Madrid

Madrid, 28033, Spain

RECRUITING

Hospital Clinico San Carlos

Madrid, 28040, Spain

RECRUITING

START Madrid Fundacion Jimenez Diaz

Madrid, 28040, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

START Madrid (Hospital San Chinarro)

Madrid, 28050, Spain

RECRUITING

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

RECRUITING

Hospital Universitario De Navarra

Pamplona, 31008, Spain

RECRUITING

START Rioja

Rioja, 26006, Spain

RECRUITING

Hospital Virgen Macarena

Seville, 41009, Spain

RECRUITING

Hospital Virgen del Rocío

Seville, 41013, Spain

RECRUITING

Instituto Valenciano de Oncología (IVO)

Valencia, 00000, Spain

RECRUITING

Incliva Biomedical Research Institute, University of Valencia

Valencia, 46010, Spain

RECRUITING

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

RECRUITING

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

RECRUITING

Guy's and St Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

RECRUITING

Sarah Cannon Research Institute UK

London, W1G 6AD, United Kingdom

RECRUITING

The Christie NHS Foundation Trust - The Christie Clinic

Manchester, M20 4BX, United Kingdom

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis; Ovarian Neoplasms; Fallopian Tube Neoplasms; Endometrial Neoplasms; Colorectal Neoplasms; Carcinoma, Acinar Cell; Hereditary Sensory and Autonomic Neuropathies

Interventions

Gemcitabine; Irinotecan

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Uterine Neoplasms; Uterine Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Camptothecin; Alkaloids

Study Officials

• Melissa Johnson, MD

  Tennessee Oncology

  STUDY CHAIR

• Antonio Gonzalez, MD, PHD

  Clinica Universidad de Navarra, Madrid

  STUDY CHAIR

• Susanna Ulahannan, MD

  Oklahoma University

  PRINCIPAL INVESTIGATOR

• Kim Reiss Binder, MD

  University of Pennsylvania / Abramson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah Cannon Development Innovations

CONTACT

844-710-6157; SCRI.InnovationsMedical@scri.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2020
• First Posted: December 8, 2020
• Study Start: January 27, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (40); ES (30); FR (5); GB (4)