Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Pancreatic Neoplasms

Disease Progression

Pancreatic Cancer

Anticonvulsants

Central Nervous System Depressants

Psychotropic Drugs

All Drugs and Chemicals

Herbal and Botanical

Amino Acids

Valproic Acid

Neratinib

Enzyme Inhibitors

Neurotransmitter Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Cola

Tyrosine

Neratinib by mouth (PO) once daily + Divalproex Sodium (Valproate) by mouth (PO) twice daily on days 1-28 of each course.

Colon Cancer (RAS-mutated) - Phase II dose expansion at recommended phase II dose (RP2D)

Glioblastoma with a RAS-mutation or EGFR alteration at RP2D

Combination of Neratinib and Divalproex Sodium (Valproate) will be given to patients with advanced solid tumors (dose escalation) and Ras-mutated cancers (dose expansion). Doses of Neratinib are escalated in small groups of patients during the dose expansion portion of the study.

Combination of Neratinib and Divalproex Sodium (Valproate) will be given to patients with advanced solid tumors (dose escalation) and Ras-mutated cancers (dose expansion).

Divalproex Sodium

massey SIIT Team

Massey Team Delta

Massey SIIT Team

Andrew Poklepovic, MD

To determine the recommended phase 2 dose (RP2D) of the combination of neratinib and sodium valproate when given to patients with advanced solid tumors. Then to explore the antitumor effects of the neratinib and sodium valproate combination in advanced solid tumors with attention to RAS-mutated tumors, EGFR-altered GBM, and ocular melanoma, as part of the phase 2 expansion cohort.

The purpose of this trial is to test the safety of combining 2 drugs, neratinib (Nerlynx) and divalproex sodium (Depakote DR), also commonly called valproate, when treating patients with advanced cancer.

In an earlier stage of this trial the purpose was to test different doses of neratinib in combination with divalproex sodium to see which doses should be used in future research trials. This trial will also help us to learn how advanced tumors respond to the combination of neratinib and divalproex sodium.

Neratinib + Valproate in Advanced Solid Tumors, w/Expansion Cohort in Ras-Mutated Ca

Phase 1/2 Study of Neratinib and Divalproex Sodium (Valproate) in Advanced Solid Tumors, With an Expansion Cohort in Ras-Mutated Cancers

There is no plan to make individual participant data available to other researchers at this time.

RP2D for the combination of neratinib and sodium valproate that is less than or the same as the maximum tolerated dose (MTD).

Determine the safety and toxicity of the combination of neratinib and sodium valproate by the number of participants with serious adverse events, and types of events as assessed by utilizing the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.

Phase 2 advanced solid tumor cohorts only: Evaluate number of participants with tumor response based on Response Evaluation Criteria in Solid Tumors (RECIST v1.1), in patients evaluable for response.

Phase 2 GBM cohort only: Evaluate number of participants with tumor control based on objective response based on Response Assessment in Neuro-Oncology (RANO) criteria or Macdonald criteria, or disease control defined as PFS ≥ 6-month in patients evaluable for response

Evaluate the number of participants with progression free survival (PFS) defined as the duration of time from start of combination treatment (Cycle 1, Day 1) to date of progression.

Puma Biotechnology, Inc.

Virginia Commonwealth University

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Genital Neoplasms, Male

Carcinoma

Fallopian Tube Neoplasms

Urogenital Neoplasms

Genital Diseases

Urogenital Diseases

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Fallopian Tube Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Antineoplastic Agents

Poly(ADP-ribose) Polymerase Inhibitors

Rucaparib

Rucaparib administered at dose and schedule last taken in parent study, or per investigator decision.

Participants discontinued rucaparib treatment and were in long-term follow-up in the parent study.

This protocol is designed to provide participants currently benefiting from rucaparib treatment in a Clovis-sponsored clinical study with continued access to treatment for as long as they continue to benefit. Participants in long-term follow-up (LTFU) in a parent study may also enroll in this study for continued data collection, as applicable based on parent study objectives.

Participants enrolled in this study are required to have completed an End-of-Treatment (EOT) Visit with associated assessments as specified in the Clovis-sponsored parent study (NCT01891344; NCT01968213; NCT02855944). Participants who are no longer receiving treatment and are in LTFU in the parent study (NCT02855944) may enroll into the LTFU portion of this study, as applicable based on parent study objectives, without repeating the EOT visit.

The starting dose of rucaparib administered at initiation of this study will be the same as the last dose received in the parent study, or as deemed appropriate by the investigator and based on available dose strength tablets. The first treatment in the rollover study will begin at the next scheduled treatment visit following the EOT Visit in the parent study.

Participants enrolled to receive continued rucaparib may be treated until disease progression, as assessed by the investigator, unacceptable toxicity, withdrawal of consent, death, loss to follow-up, or study closure by the sponsor. If a participant demonstrates disease progression per investigator assessment while receiving treatment with rucaparib but continues to derive clinical benefit, then continuation of treatment beyond progression is permitted based on investigator decision and participant consent. If a participant continues treatment post-progression, all study assessments should be continued per institutional standard of care. The participant should be discontinued from treatment once it is clear that no further clinical benefit can be achieved.

CATCH-R: A Rollover Study to Provide Continued Access to Rucaparib

CATCH-R: A Rollover Study to Provide Continued Access to Clinical Therapy With Rucaparib

An SAE was any untoward medical occurrence that occurred at any dose, or after informed consent was given and prior to dosing if the SAE was related to a study procedure, that: resulted in death; was life-threatening; required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly or birth defect; or was an important medical event that may not have resulted in death, was not life-threatening, or did not require hospitalization but may be considered an SAE, based on appropriate medical judgment. An AESI was defined as any AE of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate. A summary of all SAEs regardless of causality is located in the 'Reported Adverse Events' Section.

pharmaand GmbH

Only SAE and AESI safety data were collected, other (non-serious) AEs were not collected. Safety data were collected only for the Rucaparib arm (participants who received rucaparib during this study); safety data were not collected for the Long-term Follow-up arm (participants who did not receive rucaparib during this study). Data reported for Safety Population: all participants who received rucaparib during the study.

Participants received rucaparib at a dose and schedule last taken in the parent study, or per investigator decision.

Long-term Follow-up

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Enrolled Population: all participants who were enrolled in the study.

Only SAE and AESI safety data were collected, other (non-serious) AEs were not collected. Safety data were collected only for the Rucaparib arm (participants who received rucaparib during this study); safety data were not collected for the Long-term Follow-up arm (participants who did not receive rucaparib during this study).

Medical Information Department

SAEs

AESIs

Safety Population: all participants who received rucaparib during the study (Rucaparib arm), safety data were not collected for the Long-term Follow-up arm.

Number of Participants Experiencing SAEs and AESIs

Overall Study

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoma, Large-Cell, Anaplastic

Granuloma

Granuloma, Plasma Cell

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphoma, T-Cell

Lymphosarcoma

Anaplastic Large Cell Lymphoma

Inflammatory Myofibroblastic Tumor

Phase 1:

* To estimate the MTD/RP2D regimen of brigatinib monotherapy when administered in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors.
* To characterize the PK of brigatinib administered as monotherapy in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors.

Note that:

* If the MTD is not reached at the highest proposed test dose, no further dose-escalation will be performed.
* Pediatric PK data, compared to exposure in adults, and cumulative toxicity, will be taken into consideration to determine the RP2D regimen.

Phase 2:

• B1, ALK+ IMT: To establish the activity (ORR by RECIST 1.1) of single agent brigatinib when administered to children with ALK+ IMT.

• B2, ALK+ ALCL: To establish the efficacy (EFS) of single agent brigatinib when administered to children with ALK+ ALCL for a duration of 2 years, without SCT in consolidation.

Brigatinib is a second generation novel, orally administered, tyrosine kinase inhibitor (TKI) that potently inhibits activated variants of ALK and to a lesser extent ROS1.

Brigatinib

Maaike Boonstra

Gertruud Bakker

Youhann Vingataramin

Veronique Minard, Prof Dr

Maaike Boonstra, MSc

Gertruud Bakker, PhD

N.K.A van Eijkelenburg, MD

Michel Zwaan, Prof

This is an open-label, phase I-II dose-escalation and expansion study designed to define the recommended dose of brigatinib as monotherapy in pediatric and young adult patients with ALK+ ALCL, IMT or other solid tumors and to evaluate the pharmacokinetics (PK), (long-term) safety, and efficacy of brigatinib in these children.

This is an open-label, phase I-II dose-escalation and expansion study designed to define the recommended dose of brigatinib as monotherapy in pediatric and young adult patients with ALK+ ALCL, IMT or other solid tumors and to evaluate the pharmacokinetics (PK), (long-term) safety, and efficacy of brigatinib in these children.

Phase 1 part will be a dose escalation part using a rolling-6 design, aiming to accrue a minimum of 6 and a maximum of 18 evaluable patients in two dose-levels (and minus 1), at least 2/3 of included patients will be ≤18 years.

Phase 2 will be the tumor cohort expansion part of the study to further evaluate the safety, tolerability, and clinical activity/efficacy of brigatinib as monotherapy in two tumor-specific cohorts:

* Cohort B1: ALK+ IMT Planned sample size for Phase 2 is 12 patients with IMT. Patients who are included in the monotherapy Phase 1 IMT dose-escalation portion of the study will be included in the expansion cohort analysis if they receive the RP2D, and will count towards the total sample size of 12 patients.
* Cohort B2: ALK+ ALCL Planned sample size for Phase 2 is 22 patients with ALCL. Patients who are included in the monotherapy Phase 1 ALCL dose-escalation portion of the study will be included in the expansion cohort analysis if they receive the RP2D, and will count towards the total sample size of 22 patients.

Phase 1:

* To estimate the MTD/RP2D regimen of brigatinib monotherapy when administered in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors.
* To characterize the PK of brigatinib administered as monotherapy in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors.

Note that:

* If the MTD is not reached at the highest proposed test dose, no further dose-escalation will be performed.
* Pediatric PK data, compared to exposure in adults, and cumulative toxicity, will be taken into consideration to determine the RP2D regimen.

Phase 2:

• B1, ALK+ IMT: To establish the activity (ORR by RECIST 1.1) of single agent brigatinib when administered to children with ALK+ IMT.

• B2, ALK+ ALCL: To establish the efficacy (EFS) of single agent brigatinib when administered to children with ALK+ ALCL for a duration of 2 years, without SCT in consolidation.

Brigatinib in Pediatric and Young Adult Patients With ALK+ ALCL, IMT or Other Solid Tumors

A Phase I/II Study of Brigatinib in Pediatric and Young Adult Patients With ALK+ Anaplastic Large Cell Lymphoma, Inflammatory Myofibroblastic Tumors or Other Solid Tumors

all IPD that underlie results in a publication

Phase 1:

• To assess the MTD/RP2D regimen of brigatinib monotherapy when administered in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors.

Dose-limiting toxicities (DLTs) during the first course of therapy.

The RP2D is defined as the dose that results in equivalent (approximately ±20% of the adult values) PK exposure to 180 mg QD with a 7 day lead in of 90 mg QD in adults and with 0 or 1 DLT in 6 patients.

Phase 1:

• To characterize the PK of brigatinib administered as monotherapy in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors:

o maximum observed concentration (Cmax),

Phase 1:

• To characterize the PK of brigatinib administered as monotherapy in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors:

o area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast).

Phase 1:

* To characterize the PK of brigatinib administered as monotherapy in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors:

  * time of first occurrence of maximum observed concentration (Tmax), T ½.

• B1, ALK+ IMT:

To establish the activity (ORR by RECIST 1.1, best response) of single agent brigatinib when administered to children with ALK+ IMT:

Best response, defined as the percentage of patients with CR or PR according to RECIST 1.1 as best response during brigatinib treatment.

• B2, ALK+ ALCL: To establish the efficacy (EFS) of single agent brigatinib when administered to children with ALK+ ALCL for a duration of 2 years, without SCT in consolidation.

EFS, defined as the time between start of study treatment and first event being progressive disease (according to IPNHL criteria), relapse, death of any cause and second malignancies.

Takeda

Princess Maxima Center for Pediatric Oncology

Skin and Connective Tissue Diseases

Carcinoma, Neuroendocrine

Melanoma

Sarcoma

Carcinoma, Renal Cell

Neoplastic Cells, Circulating

Kidney Neoplasms

Carcinoma, Islet Cell

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

Neoplasm Metastasis

Neoplastic Processes

Renal Cell Carcinoma

Soft Tissue Sarcoma

Neuroendocrine Tumor

Neuroepithelioma

Patients with histologically confirmed melanoma

Patients with histologically confirmed prostate cancer

Patients with histologically confirmed solid tumor cancers other than melanoma and prostate

Patients diagnosed with non-cancerous hematologic conditions

Family members of patients undergoing treatment at Comprehensive Cancer Centers of Nevada, or other healthy volunteers

Approximately 40 cc of blood will be drawn from participants at a time when they are having blood drawn for routine or treatment-related purposes. Sequential samples may be obtained in the same manner from selected patients to allow exploration of potential correlation of CTC with response to treatment, progression-free survival and overall survival.

Blood Draw

Wolfram Samlowski, MD

The purpose of this study is to determine if circulating tumor cells (CTC) can be accurately detected and isolated from the blood of participants with melanoma using novel laboratory techniques. Blood samples will be collected from participants with melanoma, and also from participants with other solid tumor cancers and healthy volunteers for purposes of comparison.

Relevant information will be collected from participant's medical record and stored in a coded manner in a password-protected format. This information will be used to look for correlations of research results on blood samples to participant's medical condition. Test results will not be given to participants or their physicians. In some cases, CTC may be grown for long-term cell lines for further research.

A strong correlation has been established between CTC and the progression of breast, colon and prostate cancers. The number of CTC appears to act as a prognostic marker for relapse and survival in a number of epithelial cancers. Unfortunately, current CTC assays are not effective in reliably detecting circulating melanoma cells and the assay procedures damage cells prohibiting further study.

This study is designed to evaluate the sensitivity and specificity of the TrueCells assay, a novel approach to isolate and preserve cells for further research.

Primary Objectives:

* Evaluate feasibility and reproducibility of isolation of CTC using TrueCells technology.
* Optimize quantitative CTC recovery
* Provide preliminary data concerning correlation of these measurements with other methods of CTC recovery such as immunofluorescence, lipid-based staining.

Secondary Objectives:

* Explore correlation of immunofluorescent CTC assay and TrueCells CTC cultures with response to treatment by objective and immune response criteria, progression free survival, 1 and 2-year survival landmarks, and overall survival in cancer patients.
* Attempt to isolate long-term tumor cell lines for evaluation of somatic gene mutations, and gene and protein expression patterns related to individual tumors (not intended to identify familial or inherited mutations), and to test drug and biologic sensitivity.
* Isolate plasma RNA and DNA to assess expression tumor-specific markers (e.g., tyrosinase, B-FRAF, V600E, etc.) and metastasis-associated genes (e.g., MSH-1, thymidylate synthase, etc.).
* Perform ongoing developmental testing to continue to develop and optimize novel technical approaches to facilitate isolation of intact CTC.

Methods:

Blood samples will be collected from patients with melanoma (200), prostate cancer (200), other solid tumor cancers (up to 400), benign hematologic conditions (100), and healthy volunteers (up to 100). Sequential samples will be obtained from selected patients during disease progression or treatment response to allow exploration of potential correlation of CTC with response to treatment, progression-free survival and overall survival. Samples will be immediately de-identified and assigned a numerical code, dated and sent to TrueCells, LLC. Once donated, sample ownership passes to TrueCells, LLC.

Research studies include:

* CTC independently counted using immunofluorescent staining of thick smear prepared from entire buffy coat of two tubes of blood (tubes 1 \& 2), stained with appropriate primary pan-tumor monoclonal antibody or lipid markers with confirmatory secondary antibodies to exclude inadvertent inclusion of leukocyte and endothelial subsets and verify recognition of the patient's cancer.
* Leukocytes (containing CTC) isolated by density gradient centrifugation. The buffy coat is plated into TrueCells proprietary cell culture medium and tumor cells grown and propagated (tubes 3 \& 4). Cell colonies enumerated and compared to number of colonies identified by immunofluorescent staining.
* In some cases CTC may be able to be grown as long-term cell lines. These cells may be subject to further analysis such as evaluation of somatic gene mutations as well as gene and protein expression patterns to identify characteristics of individual tumors as well as drug and biologic agent sensitivity. There may be additional future in vitro experimental applications for these de-identified early-passage cell lines that have not yet been identified or anticipated in this application.
* Plasma (byproduct of leukocyte isolation process from tubes 3 \& 4) will be collected and temporarily frozen for DNA and RNA isolation for molecular assays of melanoma molecular markers and metastatic gene expression. These samples are consumed in the assay procedure.

Clinical information will be abstracted from medical records and de-identified and stored in a password-protected spreadsheet. Information to be collected includes age, gender, T, N, M status, other health conditions, serum LDH, any specific tumor markers (e.g. PSA), circulating tumor cells (if analyzed by commercial assay), somatic genetic mutations present in cancer (e.g. B-RAF V600E in melanoma patients) mitotic rate of tumor, date of tumor diagnosis, treatment history, date of regional and metastatic progression and date of death (if applicable).

Whole blood (up to 40 cc) collected in four 7.5 - 10 ml tubes. Serum samples may be stored frozen in a coded, de-identified format until DNA or RNA is extracted for assays to allow for batch processing. Samples will be consumed in the course of the research studies. Viable tumor cells may be grown as long-term cell lines.

Culture and Characterization of Circulating Tumor Cells (CTC) in Melanoma and Other Cancers

Culture and Characterization of Circulating Tumor Cells (CTC) From Patients With Malignant Melanoma and Other Cancers

TrueCells, LLC

Comprehensive Cancer Centers of Nevada

University of Pittsburgh

Wolfram Samlowski

Physician, Comprehensive Cancer Centers of Nevada; Member, Developmental Therapeutics and Genitourinary Committee, US Oncology Research Clinical; Professor, University of Nevada, Reno

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neratinib + Valproate in Advanced Solid Tumors, w/Expansion Cohort in Ras-Mutated Ca	NCT03919292	Solid Tumor, Ad...	Neratinib Divalproex Sodi...	18 Years -	Virginia Commonwealth University
CATCH-R: A Rollover Study to Provide Continued Access to Rucaparib	NCT04676334	Metastatic Cast... Ovarian Cancer Epithelial Ovar... Fallopian Tube ... Peritoneal Canc... Other Solid Tum...	Rucaparib	18 Years -	pharmaand GmbH
Brigatinib in Pediatric and Young Adult Patients With ALK+ ALCL, IMT or Other Solid Tumors	NCT04925609	Anaplastic Larg... Inflammatory My... Other Solid Tum...	Brigatinib	1 Year - 25 Years	Princess Maxima Center for Pediatric Oncology
Neratinib + Valproate in Advanced Solid Tumors, w/Expansion Cohort in Ras-Mutated Ca	NCT03919292	Solid Tumor, Ad...	Neratinib Divalproex Sodi...	18 Years -	Virginia Commonwealth University
Culture and Characterization of Circulating Tumor Cells (CTC) in Melanoma and Other Cancers	NCT01528774	Melanoma	Blood Draw	18 Years -	Comprehensive Cancer Centers of Nevada
Culture and Characterization of Circulating Tumor Cells (CTC) in Melanoma and Other Cancers	NCT01528774	Melanoma	Blood Draw	18 Years -	Comprehensive Cancer Centers of Nevada

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