Neoplasms

All Conditions

Symptoms and General Pathology

Carcinoma

Recurrence

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Olaparib

Tremelimumab

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

25 patients will receive tremelimumab alone at 10 mg/kg IV every 4 weeks for 7 doses then every 12 weeks until disease progression.

18 patients will receive tremelimumab (3 or 10 mg/kg IV) every 4 weeks for 7 doses then every 12 weeks and olaparib (150 or 300 mg orally twice a day) until disease progression.

25 patients will receive tremelimumab (every 4 weeks for 7 doses then every 12 weeks) and olaparib (daily) until disease progression. Dose of tremelimumab and olaparib will be determined during the DESE (Arm B1).

Stephanie Gaillard, MD

This study will be looking at what dose of tremelimumab and olaparib is safe and effective in patients with persistent EOC (Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma).

This clinical trial was initially intended to be a Phase 1/2 trial, but the trial never moved forward to Phase 2 prior to termination.

Study of Tremelimumab Alone or Combined With Olaparib for Patients With Persistent EOC (Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma)

An Open Label Dose Escalation/Expansion Study of Tremelimumab Alone or Combined With Olaparib for Recurrent or Persistent EOC (Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma)

Number of participants experiencing study drug-related dose limiting toxicities (DLTs). Dose escalation (phase I) portion of the trial only.

Dose escalation (phase I) portion of the trial only.

PFS rate is defined as the percentage of patients with disease progression (PD or relapse from CR as assessed using RECIST 1.1 criteria) or death due to any cause at 6 months. Per RECIST 1.1 criteria, Complete Response (CR) = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.

PFS rate is defined as the percentage of patients with disease progression (irPD or relapse from irCR as assessed using irRECIST criteria) or death due to any cause at 6 months. Per irRECIST criteria, irCR = disappearance of all lesions, irPR is =\>30% decrease in tumor burden, irPD is \>20% increase in tumor burden compared with nadir, irSD is \<30% decrease in tumor burden compared with baseline cannot be established nor \<20% increase compared with nadir. Estimation based on the Kaplan-Meier curve.

Objective Response Rate (ORR) is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. Per RECIST 1.1 criteria, CR = disappearance of all target lesions and PR is =\>30% decrease in sum of diameters of target lesions.

Objective Response Rate (irORR) is defined as the percentage of patients achieving a complete response (irCR) or partial response (irPR) based on irRECIST criteria. Per irRECIST criteria, irCR = disappearance of all lesions and irPR is =\>30% decrease in tumor burden.

Number of months from the start date of PR or CR (whichever response is recorded first) and subsequently confirmed to the first date that recurrent or progressive disease or death is documented. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, and PD is \>20% increase in sum of diameters of target lesions.

Number of months from the start date of irPR or irCR (whichever response is recorded first) and subsequently confirmed to the first date that recurrent or progressive disease or death is documented. Per irRECIST criteria, irCR = disappearance of all lesions, irPR is =\>30% decrease in tumor burden, and irPD is is \>20% increase in tumor burden compared with nadir.

DCR is defined as the number of patients achieving a complete response (CR) or partial response (PR) or stable disease (SD) based on RECIST 1.1 criteria at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, PD is \>20% increase in sum of diameters of target lesions, SD is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.

PFS is defined as the number of patients with disease progression (progressive disease \[PD\] or relapse from complete response \[CR\] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.

OS will be measured from date of first dose until death or end of followup (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.

AstraZeneca

MedImmune LLC

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Digestive System Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Peritoneal Neoplasms

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

RC88 for Injection Arm all patients will receive single-agent RC88 at 2.0 mg/kg administered on Day 1 of every 3-week cycle (Q3W).

RC88

Jianmin Fang, Ph.D

Yuzhi Li, M.D

Weidong Zhao, M.D

Yuankai Shi, Ph.D

Jianliu Wang, M.D

Xiuwei Chen, M.D

Ruixia Guo, M.D

Hui Qiu, M.D

Yi Huang, M.D

Quan Li, M.D

Jing Wang, M.D

Lijing Lijing, M.D

Ying Liu, M.D

Jie Jiang, M.D

Qi Dang, M.D

Liang Chen, M.D

Beihua Kong, M.D

Xin Lu, M.D

Wei Wang, M.D

Ke Wang, M.D

Hongying Yang, M.D

Xuejun Chen, M.D

Aijun Yu, M.D

Huafeng Shou, M.D

This study is designed to evaluate the efficacy, safety, and pharmacokinetics of RC88 monotherapy in subjects with Platinum-Resistant Recurrent Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer (PROC).

This study is designed to evaluate the efficacy, safety, and pharmacokinetics of RC88 monotherapy in subjects with Platinum-Resistant Recurrent Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer (PROC). Approximately 88 eligible patients will be enrolled，and all patients will receive single-agent RC88 at 2.0 mg/kg administered on Day 1 of every 3-week cycle (Q3W). Patients will continue to receive RC88 until disease progression, unacceptable toxicity, withdrawal of consent, death, or until the Sponsor terminates the study (whichever comes first).

Tumor assessments, including radiological assessments by CT/MRI scans will be performed at Screening and subsequently every 6 weeks (± 1 week) from Cycle 1 Day 1 (C1D1) for the first 48 weeks then every 12 weeks (± 1 week) until disease progression, death, the start of new anticancer therapy, or patient's withdrawal of consent (whichever occurs first).

All patients who discontinue RC88 will be followed for survival every 3 months (± 2 weeks) until death, lost to follow-up, withdrawal of consent for survival follow-up, or end of study (whichever comes first).

RC88 in Platinum-Resistant Recurrent Epithelial Ovarian Cancer, Fallopian Tube Cancer, and Primary Peritoneal Cancer

A Multicenter, Single-arm, Phase 2 Study to Evaluate the Efficacy, Safety and Pharmacokenetics of RC88 Monotherapy in Platinum-resistant Reccurent Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer

Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR) .The objective response rate will be mainly analyzed by the Independent Review Committee (IRC) by according to the RECIST 1.1 standard tumor evaluation.

Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR) . ORR by the investigator will be analyzed.

Duration of response was defined as the time interval between confirmed initial remission (CR or PR) disease progression (PD) or death, whichever is earlier. Evaluation by the Independent Review Committee (IRC) will be performed.

Duration of response was defined as the time interval between confirmed initial remission (CR or PR) as assessed by the investigator and investigator-assessed disease progression (PD) or death, whichever is earlier.

Progression-free survival (PFS) by Independent Review Committee (IRC) was defined as the time interval between the first administration of RC88 and IRC-assessed imaging disease progression (PD) or death, whichever is earlier

Progression-free survival (PFS) by investigator was defined as the time interval between the first administration of RC88 and investigator-assessed imaging disease progression (PD) or death, whichever is earlier

Overall survival(OS) was defined as the time interval between the first administration of RC88 and death.

Cmax will be derived from the PK blood samples collected.

Change from baseline in the physical functioning subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores. Scale scores range from 0-100. For functioning and global health status/ QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.

Immunohistochemistry was used to detect the expression of MSLN in tissue sections, and the results were used for later retrospective analysis

RemeGen Co., Ltd.

Urinary Bladder Neoplasms

Fallopian Tube Neoplasms

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

Urologic Neoplasms

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Fallopian Tube Diseases

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Belinostat

Tubulin Modulators

Antimitotic Agents

Histone Deacetylase Inhibitors

Belinostat: 1000 mg/m2 days 1-5 in a 21 day cycle; IV Paclitaxel: Administered IV 2-3 hours after belinostat infusion on day 3 in a 21-day cycle

Carboplatin: Administered IV infusion after paclitaxel on day 3 in a 21-day cycle

belinostat

e-mail contact via enquires@topotarget.com

The study seeks to assess the safety, pharmacodynamics, pharmacokinetics and efficacy of belinostat (PXD101) administered in combination with carboplatin or paclitaxel or both in patients with solid tumours followed by maximum tolerated dose (MTD) expansion (phase II) in ovarian and bladder cancer patients

The clinical trial is now in the MTD (phase II) portion of the study enrolling bladder cancer patients. Enrollment of ovarian patients is complete.

MTD Expansion I(Phase II): A total of 18-32 patients with epithelial ovarian, primary peritoneal, fallopian tube or mixed mullerian tumours of ovarian origin, in need of relapse treatment will be enrolled.

MTD Expansion II (phase II): A total of 15 patients with urothelial (transitional cell) carcinoma of the bladder will be enrolled.

A Study of Belinostat + Carboplatin or Paclitaxel or Both in Patients With Ovarian Cancer in Need of Relapse Treatment

A Phase I/II Safety, Pharmacodynamic, and Pharmacokinetic Study of Intravenously Administered PXD101 Plus Carboplatin or Paclitaxel or Both in Patients With Advanced Solid Tumours

To determine the maximum tolerated dose of belinostat (PXD101) in doses up to 1000 mg/m²/day administered in combination with standard doses of carboplatin (AUC of 5) and paclitaxel (175 mg/m2).

To determine the number of participants experiencing dose limiting toxicities of belinostat (PXD101) in doses up to 1000 mg/m²/day administered in combination with standard doses of carboplatin and paclitaxel or both.

Best overall responses were assessed by RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Clinical tumor evaluation will take place after each cycle. Formal radiological evaluation after every 2 cycles. If a response is noted, a follow-up radiographic assessment must be performed 4 weeks (+ 1 week) after the response is noted

Time to progression, defined as the interval between the first dates of treatment until the first notation of disease progression. RECIST criteria

Time to response (RECIST) was assessed as the interval between the first dates of treatment until the first notation of response.

Defined as interval from the time criteria for CR or PR are met, until the first date that recurrent or progressive disease is objectively documented.

Valerio Therapeutics

PXD101: 1000 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3

Part A: Dose Escalation (N=23)

Part B: Ovarian Cancer MTD (N=35)

PXD: 1000 mg/m² was administered as a 3 or 6 hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)

Part C: 3-6 Hours Infusion (N=7)

PXD101: 1000 mg/m² 30-minute IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Carboplatin: AUC 5 IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m² IV, 2-3 hours following the infusion of PXD101 on Cycle Day 3

Part D: Bladder Cancer MTD (N=15)

PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 0 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3

Part A: Dose Escalation 600/5/NA

PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: None administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3

Part A: Dose Escalation 600/NA/175

PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3

Part A: Dose Escalation 600/5/175

PXD101: 800 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 175 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3

Part A: Dose Escalation 800/5/175

Part A: Dose Escalation 1000/5/175

Part B: Ovarian Cancer MTD

PXD: 1000 mg/m² was administered as a 3 hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)

Part C: 3 Hours Infusion, Solid Tumors Except Ovarian Cancer

PXD: 1000 mg/m² was administered as a 6-hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)

Part C: 6 Hours Infusion Solid Tumors, Except Ovarian Cancer

Part D: Bladder Cancer MTD

Total

Age, Categorical

Sex: Female, Male

PRS Administrator Gunilla Emanuelson

Belinostat: Dose escalating up to 1000 mg/m2 days 1-5 in a 21 day cycle; IV Paclitaxel: administered in an intravenous infusion 2-3 hours after PXD101 infusion on day 3 of a 21 day cycle Carboplatin: administered in an intravenous infusion after paclitaxel on day 3 of a 21 day cycle

Part A

Maximum Tolerable Dose (MTD) Belinostat, Part A,

Primary efficacy analysis population, includes all patients who have been enrolled into the study and received at least one dose of study medication.

Best Overall Response (CR or PR)

Histone acetylase analysis was planned, but not successful due to technical issues with the method.

To Determine the Pharmacodynamic Effects of Belinostat (in the Combination) on Histone Acetylation in Peripheral Blood Mononuclear Cells (Selected Sites)

PXD: 1000 mg/m² was administered as a 3-6 hour IV infusion every 24 hours for 5 days on Day 1-5 every 3 weeks Paclitaxel: 175 mg/m² IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 Carboplatin: AUC of 5 IV administered 2-3 hours following the infusion of PXD101 on cycle Day 3 (carboplatin after paclitaxel)

Part C: 3-6 Hours Infusion, Solid Tumors Except Ovarian Cancer

Per protocol Population, includes all patients who have received at least two cycles (complete treatment days, dose reductions per protocol allowed) of study treatment and who have also had at least one post-baseline tumor assessment. Not done for Part A.

Time to Progression

Includes patients with response, i.e. 15 patients in Part B, 0 patients in Part C, and 4 patients in Part D. Not done for Part A.

Time to Response

Duration of Response

Belinostat 600 mg/30 Minutes

Belinostat 800 mg/30 Min

Belinostat 1000 mg/m2 30-minute IV infusion

Belinostat 1000 mg/30 Min

Belinostat: 1000 mg/m² was administered as a 3 hour IV infusion every 24 hours

Belinostat 1000 mg/3-hours

Belinostat 1000 mg/m² was administered as a 6-hour IV infusion every 24 hours

Belinostat 1000 mg/6-hours

The Pharmacokinetic Analysis Subset consisted of 41 patients who enrolled in the study and provided a complete or partial set of pharmacokinetic parameters.

Belinostat Cmax

The Pharmacokinetic Analysis Subset consisted of 39 patients who enrolled in the study and provided a complete or partial set of pharmacokinetic parameters

Belinostat Mean t½

The Pharmacokinetic Analysis Subset consisted of 39 patients who enrolled in the study and provided a complete or partial set of pharmacokinetic parameters.

Belinostat AUC (0-infinity)

Dose Limiting Toxicities (DLT), Part A

PXD101: 600 mg/m2 30-minute IV infusion every 24 hours for 5 days every 3 weeks (period of 3 weeks is one cycle) Carboplatin: AUC 5 (area under the curve) administered 2-3 hours after PXD101 on Cycle Day 3 Paclitaxel: 0 mg/m2 administered 2-3 hours after PXD101 on Cycle Day 3

Overall Study

Immune System Diseases

Behaviors and Mental Disorders

Hypersensitivity

Quality of Life

Anti-Infective Agents

Molgramostim

Sargramostim

Interferons

Interferon-gamma

Antiviral Agents

Immunologic Factors

GM-CSF Starting dose of 400 mg injected under the skin once a day for 7 days prior to and following each course of chemotherapy + rIFN-g (Interferon Gamma) 0.1 mg injected under the skin for 2 days before and after chemotherapy (Day 5 and Day 7 of each 7-day GM-CSF cycle) + Paraplatin (Carboplatin) AUC of 5 by 1 hour IV infusion every 28 days

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Tremelimumab Alone or Combined With Olaparib for Patients With Persistent EOC (Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma)	NCT02485990	Primary Periton...	Tremelimumab Olaparib	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
RC88 in Platinum-Resistant Recurrent Epithelial Ovarian Cancer, Fallopian Tube Cancer, and Primary Peritoneal Cancer	NCT06173037	Primary Periton... Fallopian Tube Epithelial Ovar...	RC88	18 Years -	RemeGen Co., Ltd.
A Study of Belinostat + Carboplatin or Paclitaxel or Both in Patients With Ovarian Cancer in Need of Relapse Treatment	NCT00421889	Ovarian Cancer Epithelial Ovar... Fallopian Tube ... Bladder Cancer	belinostat Paclitaxel Carboplatin	18 Years -	Valerio Therapeutics
Chemoimmunotherapy Study for Patients With Epithelial Ovarian Cancer	NCT00501644	Ovarian Cancer Fallopian Tube ... Peritoneal Canc...	Carboplatin GM-CSF (Sargram... Interferon Gamm...	-	M.D. Anderson Cancer Center
A Study of Belinostat + Carboplatin or Paclitaxel or Both in Patients With Ovarian Cancer in Need of Relapse Treatment	NCT00421889	Ovarian Cancer Epithelial Ovar... Fallopian Tube ... Bladder Cancer	belinostat Paclitaxel Carboplatin	18 Years -	Valerio Therapeutics
ABI-007 With Carboplatin as First-Line Therapy in Patients With Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Carcinoma	NCT00407407	Fallopian Tube ... Peritoneal Neop... Ovarian Neoplas...	ABI-007 Carboplatin	18 Years -	Celgene
Chemoimmunotherapy Study for Patients With Epithelial Ovarian Cancer	NCT00501644	Ovarian Cancer Fallopian Tube ... Peritoneal Canc...	Carboplatin GM-CSF (Sargram... Interferon Gamm...	-	M.D. Anderson Cancer Center
Study of Tremelimumab Alone or Combined With Olaparib for Patients With Persistent EOC (Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma)	NCT02485990	Primary Periton...	Tremelimumab Olaparib	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
RC88 in Platinum-Resistant Recurrent Epithelial Ovarian Cancer, Fallopian Tube Cancer, and Primary Peritoneal Cancer	NCT06173037	Primary Periton... Fallopian Tube Epithelial Ovar...	RC88	18 Years -	RemeGen Co., Ltd.

Spots Global Cancer Trial Database for epithelial ovarian