Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Carcinoma

Cholangiocarcinoma

Melanoma

Carcinoma, Renal Cell

Mesothelioma

Mesothelioma, Malignant

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Adenoma

Neoplasms, Mesothelial

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Bile Duct Cancer

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Malignant Mesothelioma

Intraocular Melanoma

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Niraparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

This cohort will enroll patients with mesothelioma, uveal melanoma, renal cell carcinoma (clear cell type), and cholangiocarcinoma.

This cohort will enroll patients whose tumors have a known DNA damage response mutation in any of the following genes: ARID1A, ATM, ATR, BACH1 (BRIP1), BAP1, BARD1, BLM, CHEK1, CHEK2, CDK2, CDK4, ERCC, FAM175A, FEN1, IDH1, IDH2, MRE11A, NBN (NBS1), PALB2, POLD1, PRKDC (DNA-PK) PTEN, RAD50, RAD51, RAD52, RAD54, RPA1, SLX4, WRN, or XRCC. This cohort is open to patients with any type of malignancy (except prostate).

Patients will take 300 mg of niraparib orally once daily each day of a 28 day cycle.

Thomas George, MD, FACP

This open-label, non-randomized study will investigate the use of niraparib in patients with tumors known to have mutations in BAP1 and other select DNA damage response pathway genes.

BAP1 is an ubiquitin ligase that is critical in helping to regulate the cell cycle, cellular differentiation, and cell death. This protein is also intimately involved with DNA double-strand break repair. Germline mutations in the BAP1 gene are associated with a hereditary cancer syndrome that increases the risk of uveal melanoma, mesothelioma and renal cell carcinoma. PARP is another protein that is crucial in DNA repair and enables continued cell replication and survival. It is hypothesized that PARP inhibition with niraparib will result in significant cytoreduction in patient tumors with mutations in BAP1 and other components of the DNA damage response pathway through synthetic lethality. Synthetic lethality is the inhibition of a gene that a cell relies on to compensate for the loss of another gene, resulting in the cell's demise.

Patients in both cohorts will receive niraparib.

A Trial of Niraparib in BAP1 and Other DNA Damage Response (DDR) Deficient Neoplasms (UF-STO-ETI-001)

A Phase II Trial of the PARP Inhibitor, Niraparib, in BAP1 and Other DNA Damage Response (DDR) Pathway Deficient Neoplasms (UF-STO-ETI-001)

Determine the objective response rate (ORR), which is defined as the percentage of subjects achieving a best overall response of partial or complete response (according to RECIST v1.1 criteria) from the start of the treatment until disease progression/recurrence or 30 days after the end of treatment, whichever occurs first. Per RECIST v1.1 criteria, a partial response is defined as a 30% or more decrease in the sum of the largest diameters of the target lesions. Per RECIST v1.1 criteria, a complete response is defined as the disappearance of target lesions (lymph nodes identified as lesions must have reduction in short axis to \<10 mm).

Determine the median progression-free survival. Progression-free survival is defined as the duration of time from study entry to time of progression or death or the date of last contact, whichever occurs first. Progression is defined by RECIST v1.1 criteria and is defined as an increase of at least 20% in the sum of the largest diameters of target lesions and/or the appearance of new lesions.

Determine the progression-free survival rate at 3 months after study entry in each cohort. This is the percentage of subjects that both have not had disease progression and are alive 3 months after study entry. Disease progression is defined by RECIST v1.1 criteria and is defined as an increase of at least 20% in the sum of the largest diameters of target lesions and/or the appearance of new lesions.

Determine the progression-free survival rate at 6 months after study entry in each cohort. This is the percentage of subjects that both have not had disease progression and are alive 6 months after study entry. Progression is defined by RECIST v1.1 criteria and is defined as an increase of at least 20% in the sum of the largest diameters of target lesions and/or the appearance of new lesions.

Estimate the median overall survival. Overall survival is defined as the duration of time from date of study entry until date of death or date of last contact.

GlaxoSmithKline

University of Florida

All adverse events were assessed by the principal investigator, the treating sub-investigator, and/or the study coordinator. Adverse events were assessed by physical examination, labs, and subject self-reports.

This cohort will enroll patients with mesothelioma, uveal melanoma, renal cell carcinoma (clear cell type), and cholangiocarcinoma.

Niraparib: Patients will take 300 mg of niraparib orally once daily each day of a 28 day cycle.

Cohort A

This cohort will enroll patients whose tumors have a known DNA damage response mutation in any of the following genes: ARID1A, ATM, ATR, BACH1 (BRIP1), BAP1, BARD1, BLM, CHEK1, CHEK2, CDK2, CDK4, ERCC, FAM175A, FEN1, IDH1, IDH2, MRE11A, NBN (NBS1), PALB2, POLD1, PRKDC (DNA-PK) PTEN, RAD50, RAD51, RAD52, RAD54, RPA1, SLX4, WRN, or XRCC. This cohort is open to patients with any type of malignancy (except prostate).

Niraparib: Patients will take 300 mg of niraparib orally once daily each day of a 28 day cycle.

Cohort B

Cohort B (Closed to Enrollment)

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Allison Allegra

The analysis population for both cohorts only includes those subjects with at least one RECIST response assessment at the end of treatment. 6 subjects (5 subjects in Cohort A and 1 subject in Cohort B) did not have at lease one RECIST response assessment at the end of treatment and are not included in the analysis population.

Objective Response Rate (ORR)

Progression-Free Survival

Progression-Free Survival Rate at 3 Months

Progression-Free Survival Rate at 6 Months

Overall Survival

Overall Study

Symptoms and General Pathology

Breast Neoplasms

Triple Negative Breast Neoplasms

Pathologic Complete Response

Breast Diseases

Antirheumatic Agents

Anti-Infective Agents

Capecitabine

Paclitaxel

Cyclophosphamide

Carboplatin

Pembrolizumab

Albumin-Bound Paclitaxel

Epirubicin

Immunomodulating Agents

Taxane

Antimetabolites

Tubulin Modulators

Antimitotic Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

ddEC x 4 + pembrolizumab→ PK x 4 + pembrolizumab, Two-weekly epirubicin/cyclophosphamide (EC) x 4 (epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2), followed after a three-week interval by three-weekly carboplatin x 4 (AUC = 5) together with weekly paclitaxel x 12 (80 mg/m2). Pembrolizumab is given as a 400 mg iv dosis every 6 weeks for the duration of preoperative chemotherapy.\*

CEX x 4→ PK x 4, Three-weekly cyclophosphamide/epirubicin/capecitabine (CEX) (epirubicin 75 mg/m2, cyclophosphamide 600 mg/m2 and capecitabine 900 mg/m2) x 4, followed after a three-week interval by three-weekly carboplatin x 4 (AUC = 5) together with weekly paclitaxel x 12 (80 mg/m2).Pembrolizumab is given as a 400 mg iv dosis every 6 weeks for the duration of preoperative chemotherapy.\*

\*The addition of pembrolizumab is strongly recommended to all participating patients. However, patients with a documented contraindication, or unwilling to receive immunotherapy may be included in the study without the administration of pembrolizumab.

epirubicin, cyclophosphamide, paclitaxel, carboplatin, pembrolizumab

epirubicin, cyclophosphamide, capecitabine, paclitaxel, carboplatin, pembrolizumab

Niklas Loman, MD, PhD

Lina Zander, RN

Jeanette du Pont Jensen, MD

Lone Volmer, MD

Sopie Yammeni, MD

Ulla Brix Tange, MD

Karin Peschardt, MD

Vesna Glavicic, MD

Erik Hugger Jakobsen, MD

Lars Norberg, MD, PhD

MD, PhD

Lars Norberg

Zakaria Einbeigi, MD, PhD

Per Edlund, MD, PhD

Barbro Linderholm, MD, PhD

Alaa Haidar, MD, PhD

Ida Spång Rosén, MD

Kilian Bachmeier, MD

Rosita Nordkvist, RN

Jenny Bergqvist, MD, PhD

Jenny Bergkvist, MD, PhD

Camilla Wendt, MD, PhD

Anna-Karin Wennstig, MD, PhD

Anne Andersson, MD, PhD

Henrik Lindman, MD, PhD

Cecilia Nilsson, MD, PhD

Ulrik Narbe, MD, PhD

Antonis Valachis, MD, PhD

Primary aim: To compare the effect on pathologic complete response (pCR) rate of adding capecitabine to carboplatin based preoperative chemotherapy in early ER-negative and HER2-negative breast cancer. Pembrolizumab is allowed in both arms after approval for TNBC 2022.

Primary aim: Pathological complete response rate after preoperative chemotherapy is the primary end-point of the study, which will be evaluated by comparing the effects of neoadjuvant administration of a carboplatin-based treatment and treatment adding capecitabine on pCR. After the approval of pembrolizumab in the preoperative treatment of early TNBC in 2022 the study will consist of two cohorts, one (cohort 1) without the addition of pembrolizumab, and one (cohort 2) with the addition of pembrolizumab to both study arms. The primary evaluation will be performed on the entire study population including both cohorts.

Primary translational aim: To investigate if the effects of the treatments depend on homologous repair deficiency (HRD)-status. More specifically, the aim is to test for differential effect of the two treatments on pCR for HRD-negative (HRD low and intermediate by oncoscan) and HRD-positive (HRD high by oncoscan) patients.

NordicTrip, a Translational Study of Preoperative Chemotherapy in TNBC

A Translational Randomized Phase III Study Exploring the Effect of the Addition of Capecitabine to Carboplatine Based Chemotherapy in Early "Triple Negative" Breast Cancer

Distribution of different histopathological subsets of Triple Negative Breast Cancer (TNBC).

Distribution of subsets of Triple Negative Breast Cancer (TNBC) associated with different inherited breast cancer genes (BRCA1, BRCA2, PALB2, TP53, CHEK2, ATM, RAD51 C and RAD51D).

Distribution of subsets of Triple Negative Breast Cancer (TNBC) associated with somatic mutations, (Eg BRCA1, BRCA2, PALB2, TP53, and other).

Distribution of different subsets of Triple Negative Breast Cancer (TNBC) defined based on epigenetic alterations associated with silencing of BRCA1, RAD51 and related HRD-associated genes.

pCR rate in different histopathological subsets of Triple Negative Breast Cancer (TNBC).

pCR rate in subsets of Triple Negative Breast Cancer (TNBC) associated with different inherited breast cancer genes (BRCA1, BRCA2, PALB2, TP53, CHEK2, ATM, RAD51 C and RAD51D).

pCR rate in subsets of Triple Negative Breast Cancer (TNBC) associated with somatic mutations, (Eg BRCA1, BRCA2, PALB2, TP53, and other).

pCR rate in different subsets of Triple Negative Breast Cancer (TNBC) based on epigenetic alterations associated with silencing of BRCA1, RAD51 and related HRD-associated genes.

pCR rate in subsets of Triple Negative Breast Cancer (TNBC) associated with the expression of PDL1.

Rate of pathological complete response, allowing residual dcis, at surgery after preoperative chemotherapy.

Pathological complete response rate, allowing residual dcis, stratified for homologous repair deficiency.

Rate of included patients with toxicity grade 3 or greater during study treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Trial of Niraparib in BAP1 and Other DNA Damage Response (DDR) Deficient Neoplasms (UF-STO-ETI-001)	NCT03207347	Mesothelioma Uveal Melanoma Renal Cell Carc... Cholangiocarcin...	Niraparib	18 Years - 80 Years	University of Florida
NordicTrip, a Translational Study of Preoperative Chemotherapy in TNBC	NCT04335669	Breast Cancer Triple Negative...	epirubicin, cyc... epirubicin, cyc...	18 Years - 75 Years	Lund University Hospital

Spots Global Cancer Trial Database for homologous repair deficiency