RECRUITING

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

Conditions

Advanced Cancer Metastatic Cancer Ovarian Cancer Primary Peritoneal Cancer Fallopian Tube Cancer Loss of Ataxia Telangiectasia Mutated (ATM) protein

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

A Phase I/IIa, Open-label, Multi-center Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the ATR Kinase Inhibitor ART0380 Administered Orally as Monotherapy and in Combination to Patients With Advanced or Metastatic Solid Tumors

Quick Facts

Study Start:2020-12-13

Study Completion:2025-06

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04657068

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Signed written informed consent * Have not received a previous treatment targeting the ATR/CHK1 pathway * 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 * 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 0-2 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. * Performance status of 0-2 on the ECOG scale * Advanced or metastatic cancer for which irinotecan is an appropriate treatment. Prior treatment with irinotecan is permitted. * Performance status of 0-1 on the ECOG scale * Patients with advanced or metastatic solid tumors with alterations to the ATM gene likely to predict for loss of ATM protein * Have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1 * Performance status of 0-1 on the ECOG scale * For France only ART0380 Monotherapy; Patient that is not eligible for curative treatment, for whom all standard of care therapies have failed and no therapies known to provide clinical benefit are available. * Combination arms; Patients for which irinotecan is an appropriate treatment. Prior treatment with irinotecan is permitted. * For Spain only ART0380 Combination therapy, Patient that is not eligible for curative treatment, for whom standard of care therapies have failed. * Patients with a known germline BRCA mutation, or a cancer with a known somatic BRCA mutation, or which is known to be HRD positive, and for which there is an approved PARP inhibitor should have received such treatment before participating in the study, unless contra-indicated. * Females with histologically-confirmed diagnosis of high grade serous carcinoma of the ovary, fallopian tube or primary peritoneum that is not amenable to curative therapy * Platinum-resistant disease, defined as disease progression within 6 months of last receipt of platinum-based chemotherapy. Patients must not have had primary platinum-refractory disease (disease that progressed during first-line platinum-based therapy). * No more than one prior regimen in the platinum-resistant setting. Hormonal therapies and antiangiogenic therapies (as single agents) and PARP inhibitors used as maintenance therapy are not considered as separate lines of therapy. Patients should have previously received bevacizumab and chemotherapy unless contra-indicated. * Have not received prior treatment with gemcitabine unless administered in combination with a platinum with no disease progression within 12 months after completion of that regimen * Have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1 * Performance status of 0-1 on the on the ECOG scale * Persistent or recurrent endometrial cancer with biological selection.: * Patients should have received taxane/platinum chemotherapy, unless contraindicated. * Measurable disease. * Performance status of 0-1 on the ECOG scale. * Advanced or metastatic solid cancers of any histology with biological selection * If a PD-1/PDL-1 inhibitor (eg, pembrolizumab) is approved and available for the patient's cancer, the patient should have received such treatment before participating in this study. * Radiologically evaluable disease * Metastatic CRC with alterations to the ATM gene * Participants should have previously received and failed appropriate prior lines of therapy in this setting. * Have at least 1 measurable lesion assessable using standard techniques by RECSIT v1.1. * Performance status of 0-1 on the ECOG scale. * Prior treatment with irinotecan is permitted.	* 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; known history of clinical diagnosis of tuberculosis; 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 * 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 are known to be homozygous for the UGT1A1 \6 or \28. (UGT1A1 7/7 genotype), or simultaneously heterozygous for the UGT1A1 \6 and \28. (UGT1A1 7/7 genotype) * Patients receiving inhibitors of UGT1A1 within 2 weeks before the first dose of study treatment

Inclusion Criteria

Exclusion Criteria

* Signed written informed consent
* Have not received a previous treatment targeting the ATR/CHK1 pathway
* 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
* 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 0-2 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.
* Performance status of 0-2 on the ECOG scale
* Advanced or metastatic cancer for which irinotecan is an appropriate treatment. Prior treatment with irinotecan is permitted.
* Performance status of 0-1 on the ECOG scale
* Patients with advanced or metastatic solid tumors with alterations to the ATM gene likely to predict for loss of ATM protein
* Have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1
* Performance status of 0-1 on the ECOG scale
* For France only ART0380 Monotherapy; Patient that is not eligible for curative treatment, for whom all standard of care therapies have failed and no therapies known to provide clinical benefit are available.
* Combination arms; Patients for which irinotecan is an appropriate treatment. Prior treatment with irinotecan is permitted.
* For Spain only ART0380 Combination therapy, Patient that is not eligible for curative treatment, for whom standard of care therapies have failed.
* Patients with a known germline BRCA mutation, or a cancer with a known somatic BRCA mutation, or which is known to be HRD positive, and for which there is an approved PARP inhibitor should have received such treatment before participating in the study, unless contra-indicated.
* Females with histologically-confirmed diagnosis of high grade serous carcinoma of the ovary, fallopian tube or primary peritoneum that is not amenable to curative therapy
* Platinum-resistant disease, defined as disease progression within 6 months of last receipt of platinum-based chemotherapy. Patients must not have had primary platinum-refractory disease (disease that progressed during first-line platinum-based therapy).
* No more than one prior regimen in the platinum-resistant setting. Hormonal therapies and antiangiogenic therapies (as single agents) and PARP inhibitors used as maintenance therapy are not considered as separate lines of therapy. Patients should have previously received bevacizumab and chemotherapy unless contra-indicated.
* Have not received prior treatment with gemcitabine unless administered in combination with a platinum with no disease progression within 12 months after completion of that regimen
* Have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1
* Performance status of 0-1 on the on the ECOG scale
* Persistent or recurrent endometrial cancer with biological selection.:
* Patients should have received taxane/platinum chemotherapy, unless contraindicated.
* Measurable disease.
* Performance status of 0-1 on the ECOG scale.
* Advanced or metastatic solid cancers of any histology with biological selection
* If a PD-1/PDL-1 inhibitor (eg, pembrolizumab) is approved and available for the patient's cancer, the patient should have received such treatment before participating in this study.
* Radiologically evaluable disease
* Metastatic CRC with alterations to the ATM gene
* Participants should have previously received and failed appropriate prior lines of therapy in this setting.
* Have at least 1 measurable lesion assessable using standard techniques by RECSIT v1.1.
* Performance status of 0-1 on the ECOG scale.
* Prior treatment with irinotecan is permitted.

* 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; known history of clinical diagnosis of tuberculosis; 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
* 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 are known to be homozygous for the UGT1A1 \*6 or \*28. (UGT1A1 7/7 genotype), or simultaneously heterozygous for the UGT1A1 \*6 and \*28. (UGT1A1 7/7 genotype)
* Patients receiving inhibitors of UGT1A1 within 2 weeks before the first dose of study treatment

Contacts and Locations

Study Contact

Sarah Cannon Development Innovations

CONTACT

844-710-6157

SCRI.InnovationsMedical@scri.com

Principal Investigator

Melissa Johnson, MD

STUDY_CHAIR

Tennessee Oncology

Antonio Gonzalez, MD, PHD

STUDY_CHAIR

Clinica Universidad de Navarra, Madrid

Study Locations (Sites)

University of Alabama at Birmingham

Birmingham, Alabama, 35294-3300

United States

University of Arkansas - Winthrop P. Rockefeller Cancer Institute

Little Rock, Arkansas, 72205

United States

Rocky Mountain Cancer Center

Denver, Colorado, 80218

United States

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218

United States

Florida Cancer Specialists

Fort Myers, Florida, 33901

United States

Florida Cancer Specialists

Orlando, Florida, 32827

United States

Florida Cancer Specialists

Sarasota, Florida, 34232

United States

Florida Cancer Specialists

West Palm Beach, Florida, 33401

United States

Community Health Network

Indianapolis, Indiana, 46250

United States

Hematology Oncology Associated of Central New York

New York, New York, 13057

United States

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104

United States

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

Philadelphia, Pennsylvania, 19107

United States

Tennessee Oncology, PLLC

Chattanooga, Tennessee, 37404

United States

SCRI Oncology Partners

Nashville, Tennessee, 37203

United States

Mary Crowley Cancer Research

Dallas, Texas, 75230

United States

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246

United States

Utah Cancer Specialists

Salt Lake City, Utah, 84106

United States

Virginia Cancer Specialists

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: Artios Pharma Ltd

Melissa Johnson, MD, STUDY_CHAIR, Tennessee Oncology
Antonio Gonzalez, MD, PHD, STUDY_CHAIR, Clinica Universidad de Navarra, Madrid

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-12-13

Study Completion Date2025-06

Study Record Updates

Study Start Date2020-12-13

Study Completion Date2025-06

Terms related to this study

Keywords Provided by Researchers

Loss of Ataxia Telangiectasia Mutated (ATM) protein

Additional Relevant MeSH Terms

Advanced Cancer
Metastatic Cancer
Ovarian Cancer
Primary Peritoneal Cancer
Fallopian Tube Cancer