Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Immune System Diseases

Neoplasm Metastasis

Breast Neoplasms

Hypersensitivity

Neoplastic Processes

Antineoplastic Agents

All Drugs and Chemicals

Niraparib

Mitogens

Talazoparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Part A1 will evaluate ART4215 monotherapy administered in 21 day cycles. Up to 90 participants will participate in this dose escalation arm.

Part A2 will evaluate ART4215 given in combination with talazoparib in 21 day cycles. Up to 50 participants will participate in this dose escalation arm.

In Part B1 dose expansion, up to 30 participants with solid cancers that have been treated with a PARP inhibitor for an approved indication will receive ART4215.

In Part B2 dose expansion, up to 20 participants with solid cancers with characteristics indicative of sensitivity to pol theta inhibition will receive ART4215.

In Part B3, approximately 120 participants with HER2 negative BRCA breast cancers will be randomized 1:1 to either ART4215 in combination with talazoparib or talazoparib alone.

Part A3 will evaluate ART4215 given in combination with niraparib in 21-day cycles. Up to 30 participants will participate in this dose escalation arm.

Participants will receive ART4215 by mouth daily in 21-day cycles.

ART4215

Talazoparib will be administered at a dose of 1 mg or 0.75 mg by mouth daily in 21-day cycles.

Niraparib will be administered at a dose of 200 mg or 300 mg by mouth daily in 21-day cycles.

Erika Hamilton, MD

Timothy Yap, MBBS, PhD

This clinical trial is evaluating a drug called ART4215 in participants with advanced or metastatic solid tumors. The main goals of this study are to:

* Find the recommended dose of ART4215 that can be given safely to participants alone and in combination with talazoparib
* Learn more about the side effects of ART4215 alone and in combination with talazoparib
* Learn more about the effectiveness of ART4215 alone and in combination with talazoparib
* Learn more about the effectiveness of ART4215 alone and in combination with niraparib

This is an open-label Phase I/IIa study designed to evaluate ART4215, a new first-in-class investigational medicinal product that is a potent and selective inhibitor of deoxyribonucleic acid (DNA) polymerase (pol) theta. ART4215 is being developed as an oral anti-cancer agent for monotherapy treatment of patients with cancers that harbor defects in DNA repair and in combination with anticancer medicines that cause DNA damage.

A Study of ART4215 for the Treatment of Advanced or Metastatic Solid Tumors

A Phase I/IIa, Open-label, Multi-centre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the DNA Polymerase Theta Inhibitor ART4215 Administered Orally as Monotherapy and in Combination to Patients With Advanced or Metastatic Solid Tumors

DLTs are defined as adverse events (graded according to NCI CTCAE v5.0) during Cycle 1 that are related to ART4215 monotherapy, in combination with talazoparib or in combination with niraparib

Number of adverse events as characterized by type, frequency, seriousness (graded according to NCI CTCAE v5.0) and relationship to ART4215

PFS is defined as the time from the start of randomization until the earliest objective disease progression defined by RECIST v1.1 or death by any cause in the absence of progression.

Number of adverse events as characterized by type, frequency, seriousness (graded according to NCI CTCAE v5.0) and relationship to ART4215 in combination with talazoparib

BOR will be calculated as the best response from date study treatment started until progression or censoring date in the absence of progression. BOR will be based on RECIST v1.1 and Prostate Cancer Working Group-3 (PCWG-3) (for prostate cancer).

ORR is defined as the proportion of patients who have a best response of either complete response (CR) or partial response (PR) based on RECIST v1.1 or PCWG-3. Response must be confirmed (at least two responses of CR or PR a minimum of 4 weeks apart and prior to progression/subsequent therapy) for Parts A, B1 and B2.

DCR is defined as the proportion of patients with CR, PR, or SD based on RECIST v1.1 or PCWG-3.

DOR will be defined for patients with a BOR of CR/PR as the time from the date of first documented response until date of documented progression (by RECIST v1.1 or PCWG-3) or death in the absence of disease progression. BOR should be confirmed in Parts A, B1, and B2.

Change in tumor size will be assessed for all patients with target lesion measurements at baseline.

PFS is defined as the time from the start of study treatment until the earliest objective disease progression defined by RECIST v1.1 or PCWG-3 or death by any cause in the absence of progression.

OS is defined as the time from the start of study treatment until death due to any cause.

Artios Pharma Ltd

Carcinoma

Breast Diseases

Skin Diseases

Hormones

Fulvestrant

Estrogens

Antineoplastic Agents, Hormonal

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

NUV-422 will be administered orally at escalating dose levels in combination with fulvestrant until the recommended Phase 2 combination dose (RP2cD) is determined.

500 mg fulvestrant will be administered IM on Days 1 and 15 of Cycle 1 and Day 1 of every cycle thereafter.

NUV-422 will be administered orally at the RP2cD in combination with fulvestrant.

500 mg fulvestrant will be administered IM on Days 1 and 15 of Cycle 1 and Day 1 of every cycle thereafter.

NUV-422 will be administered orally at the RP2cD.

500 mg fulvestrant will be administered IM on Days 1 and 15 of Cycle 1 and Day 1 of every cycle thereafter.

NUV-422 is an investigational drug for oral dosing.

NUV-422

NUV-422-03 is a randomized, non-comparative Phase 1/2 dose escalation and expansion study designed to evaluate the safety and efficacy of NUV-422 in combination with fulvestrant relative to NUV-422 monotherapy and fulvestrant monotherapy. The study population is comprised of adults with HR+HER2- aBC. Patients will self-administer NUV-422 orally in 28-day cycles and receive 500 mg fulvestrant intramuscularly (IM) on Days 1 and 15 of Cycle 1 and Day 1 of every cycle thereafter. Patients will be treated until disease progression, toxicity, withdrawal of consent, or termination of the study.

Sequential assignment or parallel assignment will be applied (in both Phase 1 and Phase 2), depending on the stage of the study at the time of a patient's enrollment.

Study of NUV-422 in Combination With Fulvestrant in Patients With HR+HER2- aBC

Randomized, Non-Comparative Phase 1/2 Study of NUV-422 in Combination With Fulvestrant in Patients With Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative (HR+HER2-) Advanced Breast Cancer (aBC)

Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs), and laboratory abnormalities

Nuvation Bio Inc.

This arm will evaluate AC682 monotherapy administered in 28-day cycles. Up to 30 participants will participate in this dose escalation arm.

Participants will receive AC682 by mouth daily in 28-day cycles.

AC682

This clinical trial is evaluating a drug called AC682 in participants with estrogen receptor positive/human epidermal growth factor 2 negative (ER+/HER2-) locally advanced or metastatic breast cancer. The main goals of this study are to:

* Identify the recommended dose of AC682 that can be given safely to participants
* To evaluate the side effects of AC682
* To evaluate pharmacokinetics of AC682
* To evaluate the effectiveness of AC682

This is a Phase I, first in human, open-label dose-escalation study of AC682, an orally available estrogen receptor degrader, given as a single agent.

A Study of AC682 for the Treatment of Locally Advanced or Metastatic ER+ Breast Cancer

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-Tumor Activity of AC682 in Patients With Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Locally Advanced or Metastatic Breast Cancer

Adverse events will be graded according to NCI CTCAE v5.0.

Accutar Biotechnology Inc

Patients with hormone sensitive HER2 negative primary breast cancer without lymph node metastasis. Treatment recommendations will be based on the Prosigna test result, in addition to conventional clinicopathological parameters.

Prosigna Breast Cancer Prognostic Gene Signature Assay (PAM50) risk of recurrence (ROR) analysis CE marked assay termed Prosigna™ using digital bar code technology (NanoString Technologies Inc.).

Multi-parameter tests

Bjørn Naume, MD PhD

The present project focuses on how to reduce both over- and under-treatment with adjuvant chemotherapy to a large number of breast cancer patients in Norway. A set of primary tumor prognostic factors can be analysed for potential achievement of this. Furthermore, multi-parameter tests, including detailed molecular analysis of the primary tumors might further improve the selection of patients among the lymph node negative. The study seeks to advance the development of personalised treatment of patients with early breast cancer without lymph node metastasis, by the evaluation of multi-parameter analysis as a means of identifying those patients who are likely to benefit from chemotherapy whilst sparing those who are unlikely to do so from an unnecessary and unpleasant treatment.

Several known prognostic factors are used to identify breast cancer patients with an unfavourable prognosis to receive adjuvant systemic therapy, such as tumor size, histological grade, hormone receptor status and axillary lymph node metastasis. However, a large majority of early stage breast cancer patients with small primary tumors and no lymph-node metastasis receive such treatment without being at risk of developing recurrent distant disease. Furthermore, today still only about 1/3-1/2 of the patients with occult residual cancer who receive standard adjuvant chemotherapy and/or endocrine therapy are cured as a consequence of this treatment.Therefore, the future clearly needs a more precise stratification for treatment decisions. As several alternative potent therapeutic agents exist for breast cancer, a detailed characterization of the individual breast cancer disease may improve individualized prognostication and treatment. The possibilities for detailed characterization of the primary tumor have grown substantially during the last 10 years, and the prognostic and predictive impact of various molecular-based analytical tests and algorithms has been established. In order to bring forward such strategies to the individual patient in a routine clinical setting, a project with a clear goal of establishing and evaluating the most validated molecular profiles is needed.This project will evaluate the consequences of a molecular based classification of breast cancer on treatment selection as well as on economical issues such as laboratory expenses and costs related to treatment. The safety and reproducibility of the molecular assays will also be evaluated and compared to existing prognostic and predictive markers. Finally, it will also provide an opportunity for development and prospective testing of novel prognostic or predictive subtype-specific molecular markers. The project is multidisciplinary involving personnel from the following disciplines; pathology, molecular pathology, surgery, oncology and molecular biology.

Patients with lymph node negative ER+positive HER2 negative breast cancer who have completed primary surgery, are candidates for this study. Patient can be included after written informed consent has been obtained and eligibility has been established and approved. It will be organized as a multi-center study. The study will be run as a one-armed trial. Patients with appropriate primary tumor characteristics will be informed at first postoperative visit.

Treatment recommendations will be based on the Prosigna test result, in addition to conventional clinicopathological parameters. The Prosigna test will be performed after study inclusion. Before the Prosigna test result will be informed, the treating physician has to report the type of adjuvant treatment that would have been recommended without performing the Prosigna test. After the Prosigna test results is available, the final decision of adjuvant systemic treatment plan is registered.

During and after adjuvant treatment, the follow-up of patients will be according to usual care and Norwegian Breast Cancer Group (NBCG) guideline recommendations, including annual mammography and/or breast ultrasound. The events recorded during follow-up will be reported in the Norwegian Breast Cancer Registry (NBCR) which will be the main study CRF. The annual follow-up can be organized at the hospital or with the general practioner (including telephone contact from study center).

The study will recruit a total of 2150 patients, of whom approximately 1500 will not be recommended chemotherapy. After inclusion, the patients will be followed for breast cancer related events for at least 5 years (8 years from study start).

Study assessments includes the following: Demographics (age, sex) (at inclusion), medical non-breast cancer related history (not to be included in case report form, only in the medical record). Physical examination including locoregional examination of breast/chest wall and regional lymph nodes, additional examination if clinically indicated. Functional status according to NBCR.

Mammography and if indicated breast ultrasound, if not bilateral mastectomy (before surgery and at follow-up visits).Clinical status (at follow-up).

In addition to information from the patient questionnaires, patient medication (including continuation of endocrine treatment or other breast cancer treatment related medication) will be collected through the Norwegian Prescription Database and occupational disability/sick leave through the Norwegian Labor and Welfare Administration (NAV) or FD-Trygd. As the recorded patients' data in the project will be stored for a very long time, it will later be relevant to link information against the information from the Cancer Registry of Norway and the Death Cause Registry.

At baseline, 3 months, 6 months, 1 year, 2 years and at 5 year follow-up all patients will be asked to answer questionnaires consisting of established scales with good psychometric properties and single items covering socio-demographics, comorbidity, work ability, general health and quality of life (including RAND-36 and the EQ-5D), fatigue (fatigue questionnaire73), anxiety (GAD-7 questionnaire) and depressive symptoms74, life style, sleep and breast cancer specific symptoms and complaints (EORTC QLQ-BR23, FACT-B and FACT-ES).

Formal economic evaluation of cost-benefit will be performed based on simulation of treatment paths. First, an analysis of the expected cost of the interventions (patient and hospital costs) will be performed. The second step will involve an estimation of the benefits. A likely key benefit is the potential reduction in health resource use (for instance late effects that need health service and sick-leave) resulting from fewer patients treated with chemotherapy. The size of the cost/benefits will be estimated from data provided by the questionnaires as mentioned above as well as from other external sources.

Establishment of Molecular Profiling for Individual Clinical Routine Treatment Decision in Early Breast Cancer

Measured by FACT-B and FACT-ES questionnaire

To establish the cost-effectiveness (i.e. health resource use in hospitals and society) of test-directed (Prosigna) treatment strategy compared to standard practice.Formal economic evaluation of cost-benefit will be performed based on simulation of treatment paths. Firstly, an analysis of the expected cost of the interventions (patient and hospital costs) will be performed. The second step will involve an estimation of the benefits. The size of the benefits will be estimated from data provided by the clinical study as well as from other external sources. Finally, the information on costs and benefits will be used in a formal model that simulates the various treatment paths a patient can take (with the associated probabilities, costs and benefits). These simulations will lead to conclusion about the cost per quality adjusted life of the new procedures compared to the current system as well as more general social gains (including benefits such as reduced sick pay).

Differences in the number of patients receiving the various adjuvant treatments using Prosigna-test (in addition to the routine clinicopathological variables) as basis for treatment decisions compared to standard adjuvant treatment recommendations (based on clinicopathological variables only).

Patients receiving no adjuvant chemotherapy based on Prosigna test results in combination with routine clinicopathological variables, will be recorded for metastatic events during the follow up period. To identify factors associated with survival, methods to be applied include Kaplan-Meier plots and Cox regression analyses. To statistically assess the association between breast cancer subgroups found in the analysis described above and clinical endpoints, statistical tests for comparison of survival in two or more groups (log rank test) will be used. Multivariate regression analysis will be used to adjust for other factors (such as age). Possible violations of the proportional hazards assumption inherent in both types of tests above will be detected using graphical methods as well as formal tests based on the Schoenfeld residuals.

Patients receiving no adjuvant chemotherapy based on Prosigna test results in combination with routine clinicopathological variables, will be recorded breast cancer recurrence events during the follow up period. To identify factors associated with survival, methods to be applied include Kaplan-Meier plots and Cox regression analyses. To statistically assess the association between breast cancer subgroups found in the analysis described above and clinical endpoints, statistical tests for comparison of survival in two or more groups (log rank test) will be used. Multivariate regression analysis will be used to adjust for other factors (such as age). Possible violations of the proportional hazards assumption inherent in both types of tests above will be detected using graphical methods as well as formal tests based on the Schoenfeld residuals.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of ART4215 for the Treatment of Advanced or Metastatic Solid Tumors	NCT04991480	Advanced Cancer Metastatic Canc... Breast Cancer	ART4215 Talazoparib Niraparib	18 Years -	Artios Pharma Ltd
Study of NUV-422 in Combination With Fulvestrant in Patients With HR+HER2- aBC	NCT05191004	Advanced Breast... Metastatic Brea... Breast Cancer Breast Carcinom... Cancer of the B... Cancer of Breas... Malignant Tumor... Breast Tumor	NUV-422 Fulvestrant	18 Years -	Nuvation Bio Inc.
A Study of ART4215 for the Treatment of Advanced or Metastatic Solid Tumors	NCT04991480	Advanced Cancer Metastatic Canc... Breast Cancer	ART4215 Talazoparib Niraparib	18 Years -	Artios Pharma Ltd
A Study of AC682 for the Treatment of Locally Advanced or Metastatic ER+ Breast Cancer	NCT05080842	Breast Cancer	AC682	18 Years -	Accutar Biotechnology Inc
Establishment of Molecular Profiling for Individual Clinical Routine Treatment Decision in Early Breast Cancer	NCT03904173	Breast Cancer Breast Neoplasm... Hormone Recepto...	Multi-parameter...	18 Years -	Oslo University Hospital
Study of NUV-422 in Combination With Fulvestrant in Patients With HR+HER2- aBC	NCT05191004	Advanced Breast... Metastatic Brea... Breast Cancer Breast Carcinom... Cancer of the B... Cancer of Breas... Malignant Tumor... Breast Tumor	NUV-422 Fulvestrant	18 Years -	Nuvation Bio Inc.

Spots Global Cancer Trial Database for human epidermal growth factor receptor 2 negative