Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

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

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Olaparib

Camptothecin

Adenosine

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Patients with advanced platinum resistant ovarian cancer who have received no more than 1 prior line of therapy which must be platinum-based chemotherapy

Patients with advanced ovarian cancer who have received at least 1 prior line of therapy which must include at least 1 line of platinum-based chemotherapy followed by a PARP inhibitor as maintenance treatment as their last treatment regimen

EP0057 is an investigational nanoparticle-drug conjugate with a Camptothecin payload, that is administered intravenously

EP0057

Olaparib is a PARP inhibitor (poly \[adenosine diphosphate-ribose\] polymerase inhibitor)

Olaparib tablets

EP0057-201 is a Phase 2A/B adaptive design study. Phase 2A will test EP0057 in combination with Olaparib and Phase 2B, the randomised part of the study, will test EP0057 in combination with Olaparib against SOC chemotherapy. When EP0057 is combined with Olaparib, it is envisaged that the combination should improve therapeutic responses in the recurrent ovarian cancer disease setting.

EP0057 is an investigational nanoparticle-drug conjugate administered intravenously. The rationale for developing EP0057 is to enable selective entry of EP0057 into tumour tissue and as a result create preferential accumulation of EP0057, and therefore of the payload Camptothecin, to translate into maximum tumour cell killing.

EP0057-201 is an adaptive Phase 2A/B study in patients with advanced ovarian cancer.

Phase 2A

Phase 2A will be comprised of 2 single-arm treatment cohorts:

Cohort 1 will explore EP0057 in combination with Olaparib in patients with advanced platinum resistant ovarian cancer (see inclusion criteria for definition of platinum resistant) who have received no more than 1 prior line of therapy which must be platinum-based chemotherapy (n\~=30)

Cohort 2 will explore EP0057 in combination with Olaparib in patients with advanced ovarian cancer who have received at least 1 prior line of therapy which must include at least 1 line of platinum-based chemotherapy followed by a PARP inhibitor as maintenance treatment as their last treatment regimen (n\~=30)

It is anticipated that up to approximately 60 patients (approximately 30 patients per cohort) will be enrolled into Phase 2A. Both treatment cohorts will open in parallel and patients will be enrolled into each cohort concurrently.

At the end of Phase 2A, the Safety Review Committee will guide the decision to initiate 1 or both cohorts in Phase 2B, or terminate further recruitment into the study.

Phase 2B

Phase 2B will be comprised of 2 treatment cohorts, each randomised versus SOC. One or both cohorts may be opened concurrently to recruitment:

Cohort 1 will explore EP0057 in combination with Olaparib compared with SOC chemotherapy (TBC) in patients with advanced platinum resistant ovarian cancer who have received no more than 1 prior line of therapy which must be platinum-based chemotherapy (n=\~132)

Cohort 2 will explore EP0057 in combination with Olaparib compared with SOC chemotherapy (TBC) in patients with advanced ovarian cancer who have received at least 1 prior line of therapy which must include at least 1 line of platinum-based chemotherapy followed by a PARP inhibitor as maintenance treatment as their last therapy (n=\~192)

It is anticipated that \~324 patients will be enrolled into Phase 2B. Both treatment cohorts may open in parallel and patients may be enrolled into each cohort concurrently.

EP0057 in Combination With Olaparib in Advanced Ovarian Cancer

Phase 2 Study to Evaluate the Safety & Efficacy of EP0057 in Combination With Olaparib in Advanced Ovarian Cancer Patients Who Have: Cohort 1 - Platinum Resistant Disease; Cohort 2 - Had at Least 1 Prior Line of Therapy Which Must Include at Least 1 Line of Platinum-based Chemotherapy Followed by PARP Inhibitor Maintenance

Overall Response Rate as measured using RECIST1.1

Ellipses Pharma

Respiratory Tract (Lung and Bronchial) Diseases

Digestive System Diseases

Lung Neoplasms

Stomach Neoplasms

Small Cell Lung Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Stomach Cancer

Small Cell Lung Cancer

patients with ataxia-telangiectasia mutated protein (ATM)-negative relapsed, advanced GC.

patients with relapsed extensive stage SCLC.

Olaparib is a PARP inhibitor (poly \[adenosine diphosphate-ribose\] polymerase inhibitor) Other names: Lynparza

The aim of EP0057 - 202 is to assess the safety and efficacy of EP0057 in combination with Olaparib (a PARP inhibitor) in two cancers where there is a high unmet need: extensive stage small cell lung cancer (SCLC) and ATM-negative gastric cancer (GC).

EP0057-202 is a non-comparative, multi-arm, multi-centre, open label, Phase 2 study to determine the efficacy, safety, and tolerability of EP0057 in combination with olaparib (an approved PARP inhibitor) in defined patient populations with relapsed\* GC and SCLC.

\*(see Eligibility Criteria for definition of "relapse" for each tumour type/population) The treatment cohorts will open sequentially at the Sponsor's discretion and patients may be enrolled into each cohort concurrently.

EP0057 is an investigational nanoparticle-drug conjugate administered intravenously. The rationale for developing EP0057 is to enable selective entry of EP0057 into tumour tissue and as a result create preferential accumulation of EP0057, and therefore of the payload Camptothecin, to translate into maximum tumour cell killing.

EP0057 - 202 is a Phase 2 multi arm, open label study in defined populations of patients with SCLC and GC.

The Primary objectives of Arm 1 will be to investigate the efficacy, as defined by best Objective Response Rate (ORR) of EP0057 in combination with Olaparib in patients with ataxia-telangiectasia mutated protein (ATM)-negative relapsed, advanced GC.

The Primary objectives of Arm 2 will be to investigate the efficacy, as defined by the best ORR of EP0057 in combination with Olaparib in patients with relapsed extensive stage SCLC.

The secondary objectives of both arms will be to further investigate the efficacy of EP0057 in combination with olaparib in the target patient population of each arm by assessment of the following:

* Progression-free survival (PFS)
* Overall survival (OS)
* Duration of overall response (DoR)
* Disease control rate (DCR)

Secondary objectives of arms 1 and 2 also include exploring the safety and tolerability of EP0057 when combined with olaparib in patients with GC and SCLC.

Exploratory objectives may or may not be performed during the course of the study, but if so, where available at the time of publication, results from these analyses will be reported in the clinical study report (CSR). Exploratory objectives are to:

* Examine the PK characteristics of EP0057 in combination with olaparib
* Investigate the impact of HRD (homologous recombination deficiency) status on primary and secondary endpoints, as analysed by sub-groups of HRD status.

It is estimated that approximately 115 patients will be enrolled into the study. The study will aim to recruit 34 patients across both arms of the study in stage 1. The study will then aim to recruit an additional 81 patients across both arms in the second stage.

EP0057 in Combination With Olaparib in Relapsed Advanced Gastric Cancer and Small Cell Lung Cancer

A Phase 2 Multi-arm, Open Label Study to Assess the Safety and Efficacy of EP0057 in Combination With Olaparib in Defined Populations of Patients With Relapsed Advanced Gastric Cancer and Small Cell Lung Cancer

Derived PK parameters will include: AUC0-48 for C1D1 dosing

Prostatic Neoplasms

Carcinoma, Transitional Cell

Genital Neoplasms, Male

Genital Diseases, Male

Prostatic Diseases

Male Urogenital Diseases

Transitional Cell Carcinoma

EP0057 IV Q 2weeks Day 1 and Day 15, administered in 28 day cycles, until disease progression or development of intolerable side effects

Plus olaparib (PO days 3-13\* and days 17-26\*) administered in 28 day cycles, until disease progression or development of intolerable side effects. P1: Dose Escalation P2: RP2D

(\* On days 13 and 26, only one dose of olaparib will be administered in the morning)

olaparib (PO days 3-13\* and days 17-26\* administered in 28 day cycles, until disease progression or development of intolerable side effects Plus EP0057 (IV Q 2weeks, Day 1 and Day 15) administered in 28 day cycles, until disease progression or development of intolerable side effects P1: Dose Escalation P2: RP2D (\* On days 13 and 26, only one dose of olaparib will be administered in the morning)

olaparib

Danielle F Pinkiert, R.N.

Anish Thomas, M.D.

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

Background: EP0057 consists of a sugar molecule cyclodextrin linked to a chemotherapy drug called camptothecin. The combined molecule or "nanoparticle drug conjugate" travels through the blood. Once inside cancer cells, the chemotherapy drug is released from the molecule. Olaparib is a drug that may stop cancer cells from repairing the DNA damage caused by chemotherapy. Researchers want to see how safe it is to give EP0057 and olaparib together and to see how well the combination treats a specific type of lung cancer called small cell lung cancer (SCLC).

Objectives:

To test the safety and maximum dose of EP0057 and olaparib together. To test how well they treat small cell lung cancer.

Eligibility:

Adults 18 and older with small cell lung cancer.

Design:

Participants will be screened with standard cancer care tests.

Participants will get the 2 study drugs in 28-day cycles. EP0057 will be given every 2 weeks, through a small plastic tube in an arm vein. Olaparib will be taken by mouth twice a day most days. Participants will keep a pill diary.

For Cycle 1, participants will have 3 visits. All other cycles will have 2 visits.

At study visits, participants may have:

* Blood and hair samples taken
* History and Physical exam
* Questions about health and side effects
* Pregnancy test
* Optional tumor biopsy where a piece of tumor is removed by needle after numbing the skin.
* CT scan
* Injection of EP0057 (twice per cycle)
* Olaparib prescription \<TAB\>

Participants will have a follow-up visit 4 weeks after finish taking the drugs. They will have a physical exam and blood tests. They may have a tumor biopsy. The study team will call the patient every 3 months for follow up after completing the study treatment.

Background:

Small cell lung cancer (SCLC) is an aggressive cancer with a poor prognosis.

Although highly responsive to chemotherapy initially, SCLC relapses quickly and becomes refractory to treatment within a few months.

Urothelial Carcinoma (UC) of the Bladder is the fourth most common malignancy in men and the ninth most common in women.

Prostate cancer is the most common cancer among men in the United States. While prostate cancer is initially responsive to androgen deprivation therapy (ADT), the median duration of sensitivity is 24-36 months. Moreover, patients develop resistance to current treatment options.

The use of PARP inhibitors in combination with chemotherapy builds upon pre-clinical data in lung cancer and other cancers supporting the notion that PARP inhibitors potentiate the effect of DNA damaging therapies.

Despite their highly synergistic activity in preclinical models, human studies combining PARP inhibitors and camptothecins have not translated into clinical benefit due to enhanced toxicity with the combination.

One approach to improve ability to combine camptothecins with agents that sensitize their activity like PARP inhibitors is to use alternative formulations that minimize toxicity to the normal tissues.

EP0057 is a nanoparticle drug conjugate composed of 20 (S)-camptothecin (a potent and highly selective topoisomerase I inhibitor) conjugated to a linear, cyclodextrin-polyethylene glycol-based polymer.

Olaparib is a PARP inhibitor indicated as monotherapy in patients with deleterious or suspected deleterious germline BRCA mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Olaparib has an established safety profile and it is under investigation in a number of different cancers.

Objectives:

Phase I: To determine the MTD/recommended Phase 2 dose (RP2D) of EP0057 in combination with olaparib in patients with refractory cancers.

Phase II: To determine the antitumor activity of olaparib plus EP0057 with respect to progression free survival at 16 weeks in SCLC patients with resistant or sensitive relapse.

Expansion Cohorts: To determine overall response rate of EP0057 plus olaparib in patients with mCRPC and urothelial carcinoma.

Eligibility:

Phase I

Male or female adult patients \>=18 years of age

Histologically or cytologically confirmed, advanced solid tumor that is refractory to standard therapy and/or for whom no further standard therapy is available

ECOG Performance Status of 0, 1 or 2

Phase II

Male or female patients (Bullet) 18 years old

Have a pathologically (histology or cytology) confirmed diagnosis of SCLC

Disease progression on or after at least one platinum-based standard chemotherapy regimen and/or an immune-checkpoint inhibitor for either limited or extensive stage disease.

Have measurable disease per RECIST 1.1

ECOG performance status of 0, 1 or 2

Phase II Expansion Cohorts

Have a pathologically (histology or cytology) confirmed diagnosis of urothelial carcinoma or metastatic, progressive, castrate resistant prostate cancer (mCRPC)

Disease progression on or after at least one platinum-based standard chemotherapy regimen and/or an immune-checkpoint inhibitor (except prostate cohort)

Have measurable disease per RECIST 1.1 (except prostate cohort)

Prior treatment with enzalutamide and/or abiraterone (prostate cancer cohort only)

Patients must have castrate levels of testosterone (\<50 ng/dl \[1.74 nmol/l\]) (Prostate cohort only)

Design:

Patients meeting eligibility criteria will receive EP0057 (IV Q 2weeks) plus olaparib (PO BID days 3-13 and days 17-26 administered in 28-day cycles, until disease progression or development of intolerable side effects. The MTD of the combination will be used in Phase II.

Patients in Phase II will receive, the RP2D at DL4R EP0057 12 mg/m\^2 and olaparib 250 mg BID.

Blood, tumor and hair samples will be collected at multiple time points for PK, PD analyses. Hair sample collection is optional. Tumor biopsies are optional for SCLC and UC patients and mandatory for mCRPC patients (only baseline biopsy is mandatory).

Toxicity will be graded according to CTCAE version 4.0.

Tumor assessments will be made using CT scans (chest, abdomen and pelvis) at baseline and after every 2 cycles (3 cycles for mCRPC) according to RECIST version 1.1.

After discontinuation of study treatment, follow-up for survival will be carried out every 3 months.

The maximum number of patients on the phase I portion of the trial is 30, the SCLC cohort in phase II may accrue up to 27 evaluable patients, urothelial carcinoma expansion cohort may accrue up to 34 patients and mCRPC may accrue up to 25 patients. Thus, the maximum number of evaluable patients who may enroll on this trial is 116. In order to allow for a small number of in-evaluable patients, the accrual ceiling will be set at 123.

It is anticipated that approximately 1 to 2 patients per month may enroll onto this trial; the trial is expected to complete accrual in 6-8 years.

Trial of EP0057, a Nanoparticle Camptothecin With Olaparib in People With Relapsed/Refractory Small Cell Lung Cancer

A Phase I/II Trial of EP0057, a Nanoparticle Camptothecin With Olaparib in Patients With Relapsed/Refractory Small Cell Lung, Bladder and Prostate Cancers

.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.

Determine if slightly more than 50% of patients may be identified as being without progression by 12 weeks.

Best response recorded from the start of the treatment until disease progression/recurrence.

Determine if slightly more than 50% of patients may be identified as being without progression by 16 weeks

PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

DOR is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. OS is determined from the start of treatment until death. PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
EP0057 in Combination With Olaparib in Advanced Ovarian Cancer	NCT04669002	Ovarian Cancer	EP0057 Olaparib tablet...	18 Years -	Ellipses Pharma
EP0057 in Combination With Olaparib in Relapsed Advanced Gastric Cancer and Small Cell Lung Cancer	NCT05411679	Gastric Cancer Small-cell Lung...	EP0057 Olaparib tablet...	18 Years -	Ellipses Pharma
Trial of EP0057, a Nanoparticle Camptothecin With Olaparib in People With Relapsed/Refractory Small Cell Lung Cancer	NCT02769962	Urothelial Carc... Urothelial Canc... Lung Neoplasms Small Cell Lung... Prostate Cancer	EP0057 olaparib	18 Years -	National Institutes of Health Clinical Center (CC)
Trial of EP0057, a Nanoparticle Camptothecin With Olaparib in People With Relapsed/Refractory Small Cell Lung Cancer	NCT02769962	Urothelial Carc... Urothelial Canc... Lung Neoplasms Small Cell Lung... Prostate Cancer	EP0057 olaparib	18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for ep0057

Every month we try and update this database with for ep0057 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 ep0057

Every month we try and update this database with for ep0057 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 ep0057 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.