A Study of ART0380 for the Treatment of Advanced or Metastatic Solid Tumors
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
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
Not stated in the study description — ask the study team about visits and procedures.
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests ART0380 alone or with gemcitabine or irinotecan, two cancer drugs. It aims to find a safe dose, learn about side effects, and see how well treatment works. It is for people with solid tumors that are advanced or have spread to other parts of the body.
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
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Sign a consent form and be willing to follow study visits and rules.
- Be fully active or able to walk and do light work. Be expected to live at least 12 weeks.
- Stop earlier cancer treatments for the required time and recover from most short-term side effects. Radiation used to ease symptoms must end at least 1 week before study treatment.
- Have a tumor that can be checked on scans and a tumor sample from an area not treated with radiation. Some groups need a tumor that can be measured.
- Have blood counts, kidneys, liver, and blood clotting that work well enough without blood transfusions or drugs that raise white blood cell counts.
- Meet the rules for your study group. Groups differ by cancer type, gene changes, and past treatments. Some focus on ovarian, uterine lining, colon or rectal, or pancreatic cancer.
- Have received required earlier treatments, unless they are not safe for you. Some groups limit which cancer drugs you may have had or how many treatments you may have received.
- If you or your partner could become pregnant, use highly effective birth control plus a barrier method during treatment and for the required time afterward. Do not donate eggs or sperm during treatment or for 6 months afterward.
Who can't join
- Be pregnant, breastfeeding, or planning pregnancy during the study or within 7 months after the last dose.
- Plan to father a child during the study or within 5 months after the last dose.
- Have a serious illness that could prevent you from following study rules. Listed conditions include certain HIV/AIDS-related infections in the past year, hepatitis B or C, active or long-term tuberculosis, or an earlier cancer that is not in remission.
- Have ongoing lung tissue disease or lung inflammation, even without symptoms. The provided text cuts off during this rule.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
General Inclusion Criteria: * 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 Additional inclusion criteria for participants in dose escalation (Part A1): * 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 Additional inclusion criteria for participants in dose escalation (Part A2): •Advanced or metastatic cancer for which gemcitabine is an appropriate treatment. Prior treatment with gemcitabine is permitted. Additional inclusion criteria for participants in dose escalation (Part A3): * 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. Additional inclusion criteria for participants in dose expansion (Part B1): * 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 * 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. Additional inclusion criteria for participants in dose expansion (Part B2): * 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. 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 Inclusion criteria specific to Part B3 * Persistent or recurrent endometrial cancer with biological selection.: * Patients should have received taxane/platinum chemotherapy, unless contraindicated. * Measurable disease. Inclusion criteria specific to Part B4 * 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 * Performance status of 0-1 on the ECOG scale Inclusion criteria specific to Part B5 * Metastatic CRC with alterations to the ATM gene * Participants should have previously received appropriate prior lines of therapy in this setting. * Have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1. * Patients have received a maximum of 2 prior chemotherapy regimens for the treatment of CRC. * Serum albumin ≥3g/dL within 7 days prior to first dose. * ECOG Performance Status must be stable for at least 2 weeks prior to enrollment. * Must have the clinical capacity to complete at least one 21-day treatment cycle without, in the investigator's judgment, a foreseeable need for prolonged hospitalization related to their underlying disease Inclusion criteria specific to Part B6: * Metastatic or locally advanced PDAC or acinar cell carcinoma with alterations to the ATM gene * Participants must have received at least 1 prior chemotherapy regimen for the treatment of the advanced disease OR have received neoadjuvant/adjuvant therapy with recurring occurring \<6 months following completion of this treatment. * Have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1. Previously irradiated lesions may not be considered target lesions. * Serum albumin ≥3g/dL within 7 days prior to first dose. * ECOG Performance Status must be stable for at least 2 weeks prior to enrollment. * Must have the clinical capacity to complete at least one 21-day treatment cycle without, in the investigator's judgment, a foreseeable need for prolonged hospitalization related to their underlying disease. General Exclusion Criteria: * 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 Additional exclusion criteria for participants in dose escalation (Part A3, B1, B5, and B6 in combination with irinotecan): * Patients who have symptoms or signs of clinically unacceptable deterioration of the primary disease at the time of screening. * Patients who are known to be homozygous for both UGT1A1 \*6 and \*28 (UGT1A1 7/7 genotype), or simultaneously heterozygous for both UGT1A1 \*6 and \*28. * Patients receiving strong inhibitors of UGT1A1 within 2 weeks before the first dose of study treatment * Part A3 Fed-fasted cohort only: Patients receiving acid reducing agents within 1 week before the first dose of study treatment will be excluded * Part B6: Neuroendocrine (carcinoid, islet cell) or adenosquamous carcinoma pancreatic cancer * Parts B5 and B6: Initiation of opioids in the previous 2 weeks. * Parts B5 and B6: Weight loss \>10% in the previous 8 weeks. * Parts B5 and B6: Active intestinal obstruction, ileus, or significant malabsorption.
Study sites (41)
AL
- University of Alabama at Birmingham · Birmingham, AL 35294-3300More trials in Birmingham
AR
- University of Arkansas - Winthrop P. Rockefeller Cancer Institute · Little Rock, AR 72205More trials in Little Rock
AZ
- Mayo Clinic (Arizona) · Scottsdale, AZ 85259More trials in Scottsdale
CA
- USC Norris Comprehensive Cancer Center · Los Angeles, CA 90033More trials in Los Angeles
- Sansum Clinic · Santa Barbara, CA 93105More trials in Santa Barbara
- Providence Medical Foundation · Santa Rosa, CA 95403More trials in Santa Rosa
CO
- Rocky Mountain Cancer Center · Denver, CO 80218More trials in Denver
- Sarah Cannon Research Institute at HealthONE · Denver, CO 80218More trials in Denver
FL
- Florida Cancer Specialists · Fort Myers, FL 33901More trials in Fort Myers
- Mayo Clinic (Florida) · Jacksonville, FL 32224More trials in Jacksonville
- Cancer Specialists of North Florida · Jacksonville, FL 32256More trials in Jacksonville
- Florida Cancer Specialists · Orlando, FL 32827More trials in Orlando
- Florida Cancer Specialists · Sarasota, FL 34232More trials in Sarasota
- Florida Cancer Specialists · West Palm Beach, FL 33401More trials in West Palm Beach
IL
- Hope and Healing Cancer Services · Hinsdale, IL 60521More trials in Hinsdale
IN
- Community Health Network · Indianapolis, IN 46250More trials in Indianapolis
LA
- Our Lady of the Lake · Baton Rouge, LA 70808More trials in Baton Rouge
MD
- Maryland Oncology Hematology - Primary · Columbia, MD 21044More trials in Columbia
MN
- Minnesota Oncology Hematology · Maple Grove, MN 55369More trials in Maple Grove
- Mayo Clinic (Minnesota) · Rochester, MN 55905More trials in Rochester
MO
- Washington University · St Louis, MO 63110More trials in St Louis
NY
- Hematology Oncology Associates of Central New York · East Syracuse, NY 13057More trials in East Syracuse
- Northwell Health Cancer Institute · Lake Success, NY 11042More trials in Lake Success
OH
- Oncology Hematology Care Primary · Cincinnati, OH 45242More trials in Cincinnati
- Taylor Cancer Research Center · Maumee, OH 43537More trials in Maumee
OK
- Stephenson Cancer Center · Oklahoma City, OK 73104More trials in Oklahoma City
OR
- Oregon Health & Science University · Portland, OR 97239More trials in Portland
PA
- University of Pennsylvania / Abramson Cancer Center · Philadelphia, PA 19104More trials in Philadelphia
- Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization · Philadelphia, PA 19107More trials in Philadelphia
TN
- Tennessee Oncology, PLLC · Chattanooga, TN 37404More trials in Chattanooga
- Baptist Cancer Center · Memphis, TN 38120More trials in Memphis
- SCRI Oncology Partners · Nashville, TN 37203More trials in Nashville
- Vanderbilt Medical Center · Nashville, TN 37232More trials in Nashville
TX
- Texas Oncology - Central/South Texas · Austin, TX 78705More trials in Austin
- Mary Crowley Cancer Research · Dallas, TX 75230More trials in Dallas
- Texas Oncology - Baylor Charles A. Sammons Cancer Center · Dallas, TX 75246More trials in Dallas
- Texas Oncology - Northeast Texas · Flower Mound, TX 75028More trials in Flower Mound
- Oncology Consultants · Houston, TX 77030More trials in Houston
- Texas Oncology - San Antonio · San Antonio, TX 78240More trials in San Antonio
UT
- Utah Cancer Specialists · Salt Lake City, UT 84106More trials in Salt Lake City
VA
- Virginia Cancer Specialists · Fairfax, VA 22031More trials in Fairfax