Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Amino Acids

Doxorubicin

Liposomal doxorubicin

Mitogens

Tyrosine Kinase Inhibitors

Tucatinib

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Protein Kinase Inhibitors

Tyrosine

Participants will receive tucatinib 300mg by mouth twice daily continuously in combination with Doxil 40mg/m2 given intravenously on day 1 of each cycle. Cycles will be 28 days. Up to 36 participants will be enrolled in this Phase 2 study.

Participants will receive tucatinib 300mg by mouth twice daily continuously (days 1-28) of each 28 day cycle.

Participants will receive Doxil 40mg/m2 intravenously on day 1 of each 28 day cycle (with a maximum cumulative dose of 550mg/m2).

Doxil

Sarah Cannon Development Innovations

Erika Hamilton, MD

This clinical trial is evaluating tucatinib in combination with Doxil in participants with human epidermal growth factor 2 positive (HER2+) locally advanced or metastatic breast cancer. The main goals of this study are to:

* Learn how well the combination of tucatinib and Doxil works
* Learn more about the side effects of the combination of tucatinib and Doxil

This is a Phase 2, open-label, single-arm study evaluating the combination of tucatinib with Doxil in participants with HER2+ breast cancer who have received at least one prior line of anti-HER2 therapy for locally advanced/metastatic disease or relapsed within 6 months of completion of anti-HER2 adjuvant therapy.

This study will start with a lead-in phase wherein the first 6 patients will be evaluated weekly for one treatment cycle (28 days) to ensure the regimen is safe and tolerable. If no severe and/or unexpected toxicities are observed in these initial patients, the study will continue to enroll a total of 36 patients.

Study of Tucatinib and Doxil in Participants With Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Metastatic Breast Cancer

Phase 2 Single Arm Trial With a Safety Lead-in of Tucatinib in Combination With Doxil for the Treatment of HER2+ Metastatic Breast Cancer

Proportion of participants with confirmed complete response (CR) or partial response (PR) to tucatinib in combination with Doxil according to RECIST v1.1 criteria.

Incidence of treatment related adverse events (AEs) using CTCAE v5.0.

Time from the first day of study drug administration (day 1) until disease progression as defined by RECIST v1.1, or death on study.

Seagen Inc.

SCRI Development Innovations, LLC

Symptoms and General Pathology

Neoplasm Metastasis

Neoplastic Processes

Capecitabine

Trastuzumab

Hormones

Fulvestrant

Pertuzumab

Antimetabolites

Antineoplastic Agents, Immunological

Antineoplastic Agents, Hormonal

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Pertuzumab(Perjeta): Participants will receive 840 milligrams (mg) loading dose of pertuzumab, followed every 3 weeks thereafter by a dose of 420 mg via intravenous (IV) infusion until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. It depends on the patient's choice.

Trastuzumab(Herceptin): Participants will receive trastuzumab (8 mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles) administered by IV infusion every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.

Fulvestrant(Faslodex): 500mg intramuscular injections at day 1, 15, 28 and every 4 weeks thereafter

Pertuzumab(Perjeta): Participants will receive 840 milligrams (mg) loading dose of pertuzumab, followed every 3 weeks thereafter by a dose of 420 mg via intravenous (IV) infusion until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. It depends on the patient's choice.

Trastuzumab(Herceptin): Participants will receive trastuzumab (8 mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles) administered by IV infusion every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.

Capecitabine: 1000mg/m2 orally Bid on day 1 to day 14 every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.

Participants will receive 840 milligrams (mg) loading dose of pertuzumab, followed every 3 weeks thereafter by a dose of 420 mg via intravenous (IV) infusion until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.

Participants will receive trastuzumab (8 mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles) administered by IV infusion every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.

500mg intramuscular injections at day 1, 15, 28 and 4 weeks thereafter

1000mg/m2 orally Bid on day 1 to day 14 every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.

Xuexin He, MD

Jiajia Huang, MD

The purpose of this study is to evaluate the effectiveness of anti-HER2 therapy plus Fulvestrant or Capecitabine in women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 positive (HER2+), non-visceral metastases, stage IV breast cancer.

This is a prospective, randomized, 2-arm, multicenter study to compare the safety and efficiency of anti-HER2 therapy (Trastuzumab ± Pertuzumab) plus fulvestrant versus anti-HER2 therapy (Trastuzumab ± Pertuzumab) plus capecitabine in women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 positive (HER2+), non-visceral metastases, stage IV breast cancer. Subjects will be randomized into one of two treatment arms. Arm A subjects will receive the anti-HER2 therapy plus fulvestrant. Arm B subjects will receive the anti-HER2 therapy plus capecitabine. The use of Pertuzumab depends on patients' choices.

Anti-HER2 Therapy + Fulvestrant/Capecitabine in Women With HR+, HER2+, Non-visceral Metastases Stage IV Breast Cancer

A Phase 3, Randomized, Multicenter, Open-Label Study to Compare the Efficacy and Safety of Anti-HER2 Therapy Plus Fulvestrant or Capecitabine in First-line Treatment of Women With HR+, HER2+, Non-visceral Metastases, Stage IV Breast Cancer

Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurred first.

Overall survival (OS) was defined as the time from randomization to death from any cause.

Clinical Benefit Rate (CBR) is estimated by dividing the number of patients with CR, PR, or SD (for patients with measurable disease) ≥ 24 weeks from randomization.

DOCB was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurred first (only for patients of CB)

Seriousness and attribution to the study medications of AEs

Second Affiliated Hospital, School of Medicine, Zhejiang University

Principal Investigator

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
Study of Tucatinib and Doxil in Participants With Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Metastatic Breast Cancer	NCT05748834	Breast Cancer	Tucatinib Doxil	18 Years -	SCRI Development Innovations, LLC
Anti-HER2 Therapy + Fulvestrant/Capecitabine in Women With HR+, HER2+, Non-visceral Metastases Stage IV Breast Cancer	NCT04337658	HER2-positive B...	Pertuzumab Trastuzumab Fulvestrant Capecitabine	18 Years - 75 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University
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 Tucatinib and Doxil in Participants With Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Metastatic Breast Cancer	NCT05748834	Breast Cancer	Tucatinib Doxil	18 Years -	SCRI Development Innovations, LLC

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