Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Urinary Bladder Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Lapatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Lapatinib, 1250 mg per day, per os, during 3 weeks +/- 5 days.

LAPATINIB

Geneviève CHENE, Pr

Modification of the EGF signalling pathway and / or HER 2, by Lapatinib in bladder cancer.

Patients with invasive bladder tumor , candidates for radical cystectomy. Patients will receive Lapatinib during 3 weeks +/- 5 days, before cystectomy. A comparison of tissue from the original biopsy and cystectomy after Lapatinib will allow this to occur.

TREATMENT AND STRATEGY Lapatinib in bladder carcinoma -Overall there are arguments for considering that egf pathway is involved in bladder carcinoma and so far that drugs inhibiting EGF pathway could have an impact for therapeutical endpoints.

Nevertheless it is unclear that from previous studies that adding egf inhibiting drug to chemotherapy is clinically relevant, essentially by difficulties to measure a beneficial endpoint while downstream EGF pathways have been modified by these drugs, as shown with lapatinib (see 2.1.5).

Furthermore, there is no argument for initial selection of patients based on the initial egfr and/or her 2 tumor profile, asking for more intense knowledge.

LAPATINIB TREATMENT Patients will receive lapatinib therapy at a daily standard dose of 1500 mg.

LAPATINIB TREATMENT DURATION Patients will then receive 3 weeks of lapatinib therapy + possible 5 days. As the study is a non direct benefit study, the exposition to the drug is proposed during the standard window of 3 to 4 weeks to organize a radical cystectomy in patients with muscle invasive bladder carcinoma. In this study patients, the standard procedure is not delayed for the purpose of the study.

The duration of exposition to lapatinib as to be long enough to have a continuous impact of biological events to induce indeed inhibition of EGF pathway but also to impact on more complex or more distal events as apoptosis and so to be able to measure it. This justifies a 3 weeks of treatment + possible up to 5 days more due to surgical organization procedures.

Surgery will take place on the last day of treatment, which is recommended due to the half-life of lapatinib. Nevertheless for surgical purpose, the drug could be not given on the day of surgery.

A Phase 0 of Neoadjuvant Lapatinib in Infiltrative Bladder Carcinoma Before Cystectomy

Pilot Study of Lapatinib (Tyverb®) in Neoadjuvant Treatment for Patients With Locally Bladder Carcinoma Before Cystectomy

The primary objective of the study is to evaluate the effect at a molecular level, of 3 weeks of neoadjuvant lapatinib, in locally advanced muscle-invasive transitional cell carcinoma of the bladder. A comparison of tissue from the original biopsy and cystectomy after lapatinib will allow this to occur. This effect will be evaluated by studying proliferation and apoptotic markers as well as the phosphorylation of proteins which are components of the egf signalling pathway.

Because the availability of large scale data, the correlation between lapatinib biological response and the molecular alteration of other molecules beside those involved in the egf pathway will be explored. i.e. key molecules of the pathway will also be studied at the protein level (EGFR, ERBB2, AKT ERK) as well as their phosphorylation status.

To evaluate the histological response to lapatinib at the time of surgery

University Hospital, Bordeaux

Symptoms and General Pathology

Rare Diseases

Recurrence

Glioblastoma

Glioma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroepithelioma

Bone Density Conservation Agents

Lipid Regulating Agents

Calcium

Calcium, Dietary

Pitavastatin

Hormones

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Anticholesteremic Agents

Hypolipidemic Agents

Antimetabolites

Pitavastatin 16 mg via oral route in the form of daily tablets for 6 days before SOC surgery

Pitavastatin 32 mg via oral route in the form of daily tablets for 6 days before SOC surgery

Pitavastatin 48 mg via oral route in the form of daily tablets for 6 days before SOC surgery

Pitavastatin calcium

Puspha Achaiber Sing, MD, MSc

Judith Verhagen, PhD

Puspha Achaiber Sing, MSc

Clemens Dirven, MD, PhD

The goal of this Phase 0 trial is to study if pre-operative oral pitavastatin administration reaches the tumour in patients with primary or a recurrent glioblastoma. The main question\[s\] it aims to answer are:

* Does pitavastatin reach a cytotoxic concentration in gadolinium-enhanced tumour tissue after oral administration?
* Does pitavastatin achieve a concentration that can synergize with temozolomide in the gadolinium non-enhanced area of the tumour?

Participants will receive pitavastatin in differing dosages a week before their elective surgery and blood and tumour samples will be collected.

open label, dose-finding, 3+3-like dose-escalation study design

Repurposed Drugs in Research for Cancer Clinical Trials- Pitavastatin

Phase 0 lead-in Trial of Pitavastatin in Primary and Recurrent Glioblastoma Patients

Using RNA sequencing on collected tumour samples from the gadolinium enhanced part of the tumour.

Detection of pitavastatin in gadolinium enhanced and gadolinium non-enhanced tumour. tissue in relation to serum levels after preoperative administration.

Number of AEs, SAEs and SUSARs collected at the end of the trial. Events will be scored according to CTC criteria version 5.0 (Published November 27th, 2017).

Correlation of pitavastatin concentration in plasma to pitavastatin concentration in different tumour sites(gadolinium enhanced, gadolinium non-enhanced and tumour periphery).

C.Dirven

Prof. dr.

Musculoskeletal Diseases

Craniopharyngioma

Adamantinoma

Ameloblastoma

Bone Neoplasms

Bone Diseases

In Phase 0, patients will receive one dose of tocilizumab prior to surgery.

During the Feasibility Phase, patients will receive tocilizumab every 2 weeks for up to 13 cycles (approximately 1 year). Patients will be followed for up to 5 years.

Phase 0: One dose of tocilizumab prior to surgery

Feasibility phase: Tocilizumab administered every 2 weeks for up to 13 cycles (approximately 1 year).

Tocilizumab

Ashley Mettetal

Shandi Watts

Kathleen Dorris, MD

This study will be conducted in two phases. The first phase (phase 0) will be looking at patients with new or recurrent/ progressed craniopharyngioma tumors. These patients will be given one dose of tocilizumab before they have SOC surgery of their tumor. The objective of this phase is to see if drug reaches the tumor. If phase 0 is favorable and shows that drug is penetrating the tumor, the second phase of the study (feasibility phase) will open. Both phases will remain open concurrently and patients will be able to enroll on the Phase 0 then "roll over" and enroll on the feasibility phase. During the feasibility phase patients will be administered tocilizumab every two weeks for up to 13 cycles (approximately 1 year). Patients will be followed for up to 5 years in the feasibility phase.

Phase 0 to open first and if outcomes are favorable showing drug penetration then the Feasibility Phase will open. Both arms will be open concurrently.

Tocilizumab in Children With ACP

A Phase 0/Feasibility Trial of Tocilizumab in Children and Adolescents With Newly- Diagnosed or Recurrent/Progressive Adamantinomatous Craniopharyngioma

Utilize biopsy and/or drainage to identify the presence of tocilizumab and its metabolites in adamantinomatous craniopharyngioma (ACP) tumor tissue and/or cyst fluid and/or CSF following one dose of systemically administered tocilizumab.

To define toxicities of tocilizumab therapy using CTCAE version 5.

To define levels of IL6 and other inflammatory cytokines in biopsied tissue and/or cyst fluid as measured by enzyme-linked immunosorbent assay (ELISA) following 1 dose of systemically administered tocilizumab

Utilize radiography to estimate PFS of subjects with newly diagnosed, unresectable or recurrent/progressive ACP (with or without prior radiation therapy) treated with systemic tocilizumab.

To demonstrate evidence of WNT (Wingless-related integration site) in tumor tissue using immunohistochemistry and transcription array

To demonstrate evidence of MAPK (mitogen activated protein kinases) in tumor tissue using immunohistochemistry and transcription arr

To demonstrate immune cell infiltration in tumor tissue using immunohistochemistry and flow cytometry

To characterize cytokine signaling in tumor tissue and/or cyst fluid using enzyme-linked immunosorbent assay (ELISA)To characterize cytokine signaling in tumor tissue and/or cyst fluid using enzyme-linked immunosorbent assay (ELISA)

Utilize radiography to estimate the overall response rate of subjects with newly diagnosed, unresectable or recurrent/progressive ACP (with or without prior radiation therapy) treated with systemic tocilizumab.

Utilize radiography to estimate the 1-year disease stabilization rate of subjects with newly diagnosed, unresectable or recurrent/progressive ACP (with or without prior radiation therapy) treated with systemic tocilizumab.

National Cancer Institute (NCI)

University of Colorado, Denver

Adenocarcinoma

Uterine Neoplasms

Cystadenocarcinoma, Serous

Endometrial Neoplasms

Cystadenocarcinoma

Genital Neoplasms, Female

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Neoplasms, Cystic, Mucinous, and Serous

Adenocarcinoma of the Appendix

Niraparib

Poly(ADP-ribose) Polymerase Inhibitors

Single arm. Following the initial assessment and endometrial biopsy the participants will receive niraparib for 28 days. After the treatment period the patients will be surgically staged. All participants will receive the standard of care.

Low dose oral niraparib capsules (2 x 100 mg) once a day for 28 days

Niraparib oral capsule

Shannon Salvador, MD MSc

David Knigin, MD PhD

Walter Gotlieb, MD PhD

The study will investigate the effect of niraparib on tumor tissue in chemotherapy naïve, newly diagnosed, high-grade endometrial cancer patients. Biomarkers of cognate molecular pathways as well as investigational assays will be used to study the antineoplastic effect of the drug.

Niraparib is a FDA approved Poly(ADP-ribose) polymerase inhibitor (PARPi) for the treatment of platinum-sensitive ovarian serous carcinoma. The safety profile of niraparib was established in phase III clinical trials. The therapeutic effect of niraparib on serous endometrial carcinoma is now being investigated in several clinical trials. However, the antineoplastic effect and the safety profile of niraparib in chemotherapy naïve high-grade endometrial cancer patients is unknown. By employing a phase 0 exploratory trial design, the investigators will study the niraparib's effect on endometrial cancer in chemotherapy naïve patients using molecular biomarkers as sentinels for the antineoplastic effect. Women diagnosed by endometrial biopsy with high-grade endometrial cancer will receive niraparib for 28 days. Staging surgery will be performed 4-6 weeks after the diagnosis (standard of care). The investigators will use the pre-operative biopsy and the surgical specimen to perform comparative multidimensional analysis of endometrial tumors before and after exposure to niraparib.

Niraparib in High-grade Endometrial Cancer Trial

The Molecular and the Clinical Effects of Preoperative Niraparib in Patients With High-grade Endometrial Cancer: Phase 0 Exploratory Trial

Gene expression profile by RNA sequencing extracted from snap-frozen tumor tissue. Unsupervised hierarchical clustering of 2-fold changed genes will be used to detect the pathways affected by niraparib treatment.

Mutational signature and the altered genes of the DNA repair pathway will be identified by DNA next generation sequencing. Genomic findings will be correlated with molecular analysis for discovery of biomarkers for niraparib sensitivity in chemotherapy-naïve endometrial cells.

Cancer cell proliferation will be quantitatively assessed using immunohistochemical staining for cell-cycle proteins.

Ki-67 (MIB) stains nuclei of cells in G1-S-G2 phases of the cell-cycle. The proliferation index will be calculated as percent of tumor positive cells. The primary outcome fold change in proliferation index after exposure to niraparib. The quantification will be done by image analysis software with pathologist supervision.

The levels of different cell-cycle related proteins increase and decrease throughout the cell cycle, each having its own expression pattern.

Tumor specimens will be stained for Cyclin D1, Geminin and p21 proteins. The proportion of positive nuclei of each marker after exposure to niraparib will be estimated. The results will be integrated to study the effect of niraparib on endometrial cancer cells proliferation.

Cleaved caspase-3 (cCas-3) marks cells that activated the programmed cell-death process. cCas-3 positive tumor cells will be compared before and after the exposure to niraparib.

Comparison of the thickness of endometrial lining before and after treatment

Investigation of the effect of preoperative niraparib on CA125 levels in patients with high grade endometrial carcinoma

Assessment of adverse effects of niraparib in chemotherapy naïve patients according to CTCAE 5.0

Patients' well being will be assessed by a validated questionnaire: Functional Assessment of Cancer Therapy - General (FACT-G). https://www.facit.org

Patients' well being will be assessed by a validated questionnaire: Functional Assessment of Cancer Therapy - Endometrial (FACT-en). https://www.facit.org

Sir Mortimer B. Davis - Jewish General Hospital

Principal Investigator

Gland and Hormone Related Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

Hypoglycemic Agents

Antipyretics

Anti-Inflammatory Agents

Antirheumatic Agents

Fibrinolytic Agents

Analgesics

Platelet Aggregation Inhibitors

Metformin

Letrozole

Aspirin

Olaparib

Aromatase Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Acetylsalicylic acid tablets 160 mg x1 orally

Acetylsalicylic acid

Line Bjørge, MD, PhD

The study will be conducted in women with advanced (stage IIIa-IV) ovarian cancer of the histologic subtype high grade serous carcinoma (HGSOC) who are going through a diagnostic laparoscopy. They will recieve treatment with a study agent for 10-14 days before surgery. They will be allocated to different study groups according to the diagnostic evaluation performed as standard of care at the department. The study is randomized and unblinded.

The primary investigational agents are:

1. Metformin tablets, 850 mg x 2 orally.
2. Acetylsalicylic acid tablets, 160 mg x1 orally
3. Olaparib capsules, 300 mg x 2 orally
4. Letrozol tablets, 2.5 mg x 1 orally

The women who agree to participate in the study prior to the laparoscopic evaluation, will be allocated to different study groups according to the diagnostic evaluation performed as standard of care at the department. During inclusion in the first study cohort, the olaparib cohort (n=32), an additional 16 women are randomized as controls and will not receive neither any study drug nor placebo. The study is unblinded. There will not be randomized controls into the other study cohorts, as the control group collected will be utilized as controls for all study agents.

The women in Arm I will be included in the WOO trial, and will be treated with the study agent for 10-14 days prior to tumor reductive surgery, starting the day of laparoscopic surgery (+1 day). The treatment will be discontinued at the time of tumor reductive surgery.

Currently fourmore agents are evaluated as of particular interest, as well as feasible to introduce, in the WOO study set up: metformin, acetylsalicylic acid, olaparib, and letrozol. The first agent listed in the protocol, metformin, will be given to 32 consequtive women, and drug related analyses will thereafter be performed. The next 32 women included in the study will receive the next agent on the list, acetylsalicylic acid, while analyses for the metformin group is ongoing, and after the acetylsalicylic acid study group has been included the next agent on the list is introduced. Should any of the included women be non-eligable to receive one study drug, they will either receive the next agent on the list of the four study drugs, if eligable, or be included as control.

The women in Arm II who agree to participate in the study will not receive the study medication, but standard neoadjuvant chemotherapy until having decreased tumor load radiologically estimated and scheduled for optimal debulking procedure according to standard treatment of this group of patients. Samples from these women will be used as control in the translational part of the where we aim to identify potential molecular pathway(s) and cell type(s) that may be responsible for suboptimal debulking.

During the cancer-directed surgical procedure in participants in both Arms additional tissue samples from matching sites, preferably from tissues removed as part of the operation, as well as blood and urine samples, are obtained for comparative analysis. By use of the collected samples we can evaluate the clinical and molecular impact of the study agents among those triaged to primary cytoreductive surgery. Promising therapeutic targets identified might later be explored separately in one of the consequtive treatment study groups.

After the debulking surgery all women will follow the recommended standard of care, including chemotherapy and consolidating bevacisumab where indicated.

The first treatment cohort has a randomized design 2:1 (olaparib 32:control 16). The study is unblinded. In the following treatment arms are initiated each will included patients (n=32) will be offered the study-prespecified treatment drug.

IMPACT: A Randomized WOO Study of Novel Therapeutic Agents in Women Triaged to Primary Surgery for EOC

IMPACT: A Phase 0 Randomized Window-of-Opportunity Study of Novel and Repurposed Therapeutic Agents in Women Triaged to Primary Surgery for Advanced Epithelial Ovarian Cancer in Stages IIIa - IV.

A characterization of the tumor tissues from each patient will be performed (in pair). For each drug a specific biomarker is selected. The changes in expression of the defined biomarkers represent the primary outcome parameters. biomarkers related to the study agents and operability

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 0 of Neoadjuvant Lapatinib in Infiltrative Bladder Carcinoma Before Cystectomy	NCT01245660	Bladder Carcino... Infiltrative Bl... Cystectomy	LAPATINIB	18 Years -	University Hospital, Bordeaux
Repurposed Drugs in Research for Cancer Clinical Trials- Pitavastatin	NCT05977738	Glioblastoma Mu... Recurrent Gliob...	Pitavastatin ca...	18 Years -	Erasmus Medical Center
Repurposed Drugs in Research for Cancer Clinical Trials- Pitavastatin	NCT05977738	Glioblastoma Mu... Recurrent Gliob...	Pitavastatin ca...	18 Years -	Erasmus Medical Center
Repurposed Drugs in Research for Cancer Clinical Trials- Pitavastatin	NCT05977738	Glioblastoma Mu... Recurrent Gliob...	Pitavastatin ca...	18 Years -	Erasmus Medical Center
Tocilizumab in Children With ACP	NCT03970226	Adamantinomatou...	Tocilizumab	2 Years - 21 Years	University of Colorado, Denver
Niraparib in High-grade Endometrial Cancer Trial	NCT05289648	Endometrial Can... Serous Adenocar... Uterine Neoplas...	Niraparib oral ...	18 Years -	Sir Mortimer B. Davis - Jewish General Hospital
IMPACT: A Randomized WOO Study of Novel Therapeutic Agents in Women Triaged to Primary Surgery for EOC	NCT03378297	Ovarian Cancer	Metformin Acetylsalicylic... Olaparib Letrozole	18 Years -	Haukeland University Hospital

Spots Global Cancer Trial Database for phase 0

Every month we try and update this database with for phase 0 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for phase 0

Every month we try and update this database with for phase 0 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for phase 0 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.