Neoplasms

All Conditions

Immune System Diseases

Rare Diseases

Carcinoma

Hypersensitivity

Carcinoma, Acinar Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Acinic Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Administered orally (300 mg) twice daily continuously for 21-day cycles for up to 2 years.

NCI Medical Oncology Referral Office

Christine C Alewine, M.D.

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Background:

Pancreatic Acinar Cell Carcinoma (PACC) is a rare pancreatic tumor. People with PACC usually present with advanced disease, and their prognosis is poor. Researchers want to learn if a cancer drug called olaparib can help.

Objective:

To see if olaparib is an effective treatment for PACC.

Eligibility:

People aged 18 and older with PACC whose cancer did not respond to previous treatments or is not eligible for surgery.

Design:

Participants will be screened with the following:

Medical history

Physical exam

Blood and urine tests

Electrocardiogram (to test heart function)

Computed tomography (CT) scans

Pregnancy test (if needed)

Tumor biopsy (if a sample is not available)

Treatment will be given in 21-day cycles. Participants will take olaparib by mouth twice daily for each cycle. They will keep a medicine diary. They will receive treatment for up to 2 years. They may stop treatment early if their cancer gets worse or they have serious side effects.

Participants will have study visits at the beginning of each cycle. At visits, they will repeat some screening tests. They will be asked about any changes in medicines they are taking and how they are feeling. They will have CT scans every 8 weeks starting in cycle 2.

Participants will give blood samples for research. They may have optional tumor biopsies.

Participants will have 2 follow-up visits in the 30 days after treatment ends or before they begin a new anti-cancer treatment. Then they will be contacted every 3 months by phone for 1 year.

Participation will last for up to 3 years.

Background:

* Pancreatic Acinar Cell Carcinoma (PACC) is a rare pancreatic tumor, representing 0.5-1% of all pancreatic malignancies.
* PACC is commonly advanced at presentation and median overall survival in this population is poor.
* PACC is pathologically and biochemically distinct from pancreatic adenocarcinoma.
* No clinical trials for PACC have ever been reported.
* Patients are most commonly treated with combination regimens used for either pancreatic or colon adenocarcinoma with poor (approximately 30%) response rates in the first-line setting.
* PACC pathological specimens demonstrate evidence of high chromosomal instability, a hallmark of DNA repair deficiency.
* Data derived from ovarian and prostate cancer patients has demonstrated that mutations in DNA repair genes can define subgroups of cancer patients with distinct vulnerabilities to DNA damage response inhibitors.
* Olaparib is a Poly-ADP ribose polymerase (PARP)-1 inhibitor that has been FDA approved for the treatment of BRCA-mutant homologous recombination repair (HRR) deficient cancers.
* As PACC has multiple hallmarks of HRR deficiency, we hypothesize that PACC will be sensitive to PARP inhibition with olaparib.
* Pre-clinical modeling of PACC has been very limited with no currently available animal models or cell lines, which precludes testing this hypothesis in the laboratory setting.

Objective:

- To assess the anti-tumor activity of single agent olaparib, a PARP inhibitor, in participants with advanced pancreatic acinar cell carcinoma (PACC)

Eligibility:

* Participants must have advanced previously treated PACC
* Age \>=18 years
* Adequate organ and bone marrow function

Design:

* This is a phase II, single arm, single center study of olaparib in subjects with advanced previously treated PACC.
* All subjects will take olaparib by mouth twice daily for up to two years or until disease progression or intolerable side effects.
* Subjects will be assessed for safety (continuously) and efficacy (every 8 weeks).
* Up to 13 evaluable participants will be enrolled.

Olaparib in Subjects With Advanced Pancreatic Acinar Cell Carcinoma

Phase II Study of Olaparib in Subjects With Advanced Pancreatic Acinar Cell Carcinoma

.All IPD recorded in the medical record will be shared with intramural investigators upon request.@@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

Disease control rate, median duration of treatment response, median progression-free survival (PFS) and median overall survival (OS)

National Cancer Institute (NCI)

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

Patients with epithelial ovarian adenocarcinoma with archival tumor tissue available for analysis were identified through the Hellenic Cooperative Oncology Group (HeCOG)'s tumor repository. Patients had received treatment at HeCOG-affiliated institutions following standard international guidelines.

Tumor tissue processing and all NGS genotyping were performed at the Laboratory of Molecular Oncology (Hellenic Foundation for Cancer Research / AUTH). Paraffin H\&E sections from the retrieved tissue blocks were centrally reviewed for tumor histology and tissue adequacy for DNA extraction and were marked for macrodissection along with tumor DNA content \[(former tumor cell content (TCC%)\] assessment. DNA was extracted from macrodissected tissue fragments with the QIAamp® DNA mini kit (Qiagen, Hilden, Germany), measured in a Qubit fluorometer (Thermo Fisher Scientific, Paisley, UK), and genotyped with NGS in an Ion Torrent Proton sequencer (Thermo Fisher Scientific) by using a previously published custom panel (Kotoula, Lakis et al. 2019). Following stringent variant quality filtering (Kotoula, Chatzopoulos et al. 2021), 500 tumors

Tumor molecular profiling

ELENA FOUNTZILAS, MD

Molecular alterations in Homologous Recombination Repair (HRR) genes have been associated with clinical benefit from chemotherapy and/or Poly (ADP-ribose) polymerase (PARP) inhibitors in patients with epithelial ovarian cancer. Therefore, the performance of tumor molecular profiling is currently recommended by international guidelines at initial diagnosis, among other reasons, for the modification of the treatment plan. The investigators' hypothesis was that tumor molecular profiling reveals additional parameters that can improve the predictive and prognostic role of the mere presence of HRR gene mutations. The study aimed to investigate the prognostic and predictive role of clonality of pathogenic variants in HRR genes and/or concurrent pathogenic variants in other clinically relevant genes.

Pathogenic Variants in Homologous Recombination Repair Genes in Patients With Epithelial Ovarian Cancer

Clonality of Pathogenic Variants in Homologous Recombination Repair Genes in Patients With Epithelial Ovarian Cancer

The time from ovarian cancer diagnosis to the date of death from any cause

The time from initiation of first-line chemotherapy to the first documented progression, death from any cause or last contact, whichever occurred first

Hellenic Cooperative Oncology Group

Prostatic Neoplasms

Genital Neoplasms, Male

Genital Diseases, Male

Prostatic Diseases

Male Urogenital Diseases

Anti-Infective Agents

Formaldehyde

Patients with recurrent locally advanced, metastatic and/or high-grade operable prostate cancer and available formalin-fixed paraffin-embedded tumor tissue. Patients received treatment at Hellenic Cooperative Oncology Group (HeCOG)-affiliated departments of oncology. Tumor molecular profiling was performed.

Tumor molecular profiling was assessed using the ForeSENTIA® Prostate panel developed by NIPD Genetic

The aim of the study was to evaluate the prevalence, the prognostic and predictive value of gene alterations in unselected patients with prostate cancer. Patients with histologically confirmed prostate cancer, treated at Hellenic Cooperative Oncology Group (HeCOG)-affiliated departments, were included. The presence of gene alterations was assessed using the ForeSENTIA® Prostate panel developed by NIPD Genetic.

Data on tumor molecular profiling of European patients with prostate cancer is limited. The aim of the study was to evaluate the prevalence, the prognostic and predictive value of gene alterations in unselected patients with prostate cancer. Patients with histologically confirmed prostate cancer, treated at Hellenic Cooperative Oncology Group (HeCOG)-affiliated departments, were included. The presence of gene alterations was assessed using the ForeSENTIA® Prostate panel developed by NIPD Genetic. The primary endpoint was the prevalence of gene alterations in homologous recombination repair (HRR) genes. Secondary endpoint was overall survival.

FFPE tumor blocks from patients with recurrent locally advanced, metastatic and/or high-grade operable prostate cancer

Tumor Molecular Profiling in Patients With Prostate Cancer

Investigation of Mutations in DNA Damage Repair Genes and Other Actionable Molecular Aberrations as Biomarkers in Patients With Prostate Cancer

Time from diagnosis to the date of death, through the completion of the study

Number of patients with somatic mutations

NIPD Genetics

Skin and Connective Tissue Diseases

Digestive System Diseases

Breast Neoplasms

Pancreatic Neoplasms

Cholangiocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Pancreatic Cancer

Bile Duct Cancer

Niraparib

Niraparib 100mg or 200mg, PO, qd，d1-d21

Anlotinib

Jiayang Zhang, M.D.

Anqiang Wang, M.D.

Huiping Li, M.D.

Jiafu Ji, M.D.

Homologous Recombination Repair (HRR) gene mutations can be detected in many solid tumors, patients with HRR gene mutations may benefit from PARP inhibitor. Antiangiogenic drugs can induce hypoxia and increase the sensitivity to PARP inhibitor. The combination of PARP inhibitor and antiangiogenic drug can play a synergistic anti-tumor role and achieve good efficacy in HRR gene-mutated tumors. The purpose of the study is to determine the dose limiting toxicity (DLT) and maximum tolerable dose (MTD) of Niraparib plus Anlotinib in HRR gene-mutated advanced solid tumors, and evaluate the safety and effectiveness of this combination therapy preliminarily.

This is a single-arm, single-center, phase I study to investigate the DLT and MDT, safety and efficacy of Niraparib combined with Anlotinib in the treatment of advanced solid tumors with HRR gene mutations. In this study, 52 histological or cytological diagnosis, previous treatment failure patients of HER2 negative breast cancer, cholangiocarcinoma, gastric adenocarcinoma and pancreatic cancer are included and receive Niraparib combined with Anlotinib. Patients are required to carry pathogenic or suspected pathogenic gBRCA or sBRCA mutations, or HRR gene mutations defined by the inclusion criteria. The study will be divided into two phase. The first phase will include 6-12 patients on a 21-day cycle to determine the DLT and MTD. In the second phase, 40 patients will be included to treated with Niraparib plus Anlotinib until disease progression or intolerable toxicity or withdrawal of the trial.

Niraparib Combined With Anlotinib in Homologous Recombination Repair (HRR) Gene-mutated Advanced Solid Tumors

A Single Arm, Single Center, Phase I Trial of Niraparib Plus Anlotinib in Advanced Solid Tumors With Homologous Recombination Repair (HRR) Gene Mutations

Within six months after the trial complete, study protocol, informed consent form and clinical study report will be shared.

The frequency and severity of adverse events and toxicity based upon NCI CTCAE version 5.0 during subjects receiving the treatment

The ORR is a combination of CR (the target lesion completely disappeared over 4 weeks) and PR (Target lesions were reduced by more than 30% for more than 4 weeks).

PFS is defined as the time from enrollment to first documentation of tumor progression, or to death due to any cause in the absence of previous documentation of objective tumor progression.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Olaparib in Subjects With Advanced Pancreatic Acinar Cell Carcinoma	NCT05286827	Pancreatic Acin...	Olaparib	18 Years -	National Institutes of Health Clinical Center (CC)
Pathogenic Variants in Homologous Recombination Repair Genes in Patients With Epithelial Ovarian Cancer	NCT04716374	Epithelial Ovar...	Tumor molecular...	18 Years -	Hellenic Cooperative Oncology Group
Tumor Molecular Profiling in Patients With Prostate Cancer	NCT05573789	Prostate Cancer Metastatic Pros...	Tumor molecular...	18 Years -	Hellenic Cooperative Oncology Group
Tumor Molecular Profiling in Patients With Prostate Cancer	NCT05573789	Prostate Cancer Metastatic Pros...	Tumor molecular...	18 Years -	Hellenic Cooperative Oncology Group
Tumor Molecular Profiling in Patients With Prostate Cancer	NCT05573789	Prostate Cancer Metastatic Pros...	Tumor molecular...	18 Years -	Hellenic Cooperative Oncology Group
Niraparib Combined With Anlotinib in Homologous Recombination Repair (HRR) Gene-mutated Advanced Solid Tumors	NCT04764084	HER2-negative B... Gastric Adenoca... Cholangiocarcin... Pancreatic Canc...	Niraparib Anlotinib	18 Years - 70 Years	Peking University Cancer Hospital & Institute

Spots Global Cancer Trial Database for homologous recombination repair