Intraperitoneal Chemotherapy Alone or in Combination With Bevacizumab for Ovarian Cancer With Peritoneal Adhesion

Chinese PLA Generation Hospital

Background: Malignant peritoneal adhesion is a common complication and prognostic factor of ovarian cancer and other primary abdominal tumors. The incidence of peritoneal adhesion in advanced primary peritoneal tumor is 32-56%, which has increased by more than 10 times in the recent decade. Malignant peritoneal adhesion is closely associated with the morbidity and mortality of malignant intestinal obstruction. The peritoneal adhesion may aggravates the abdominal symptoms and reduce quality of life. Further, the peritoneal adhesion may impede treatment of primary tumor, such as operation or chemotherapy, lead to a poor prognosis.

Objective: This study aims to treat malignant peritoneal adhesion with the combination of antiangiogenic agent and chemotherapy, evaluate the efficacy and safety of intraperitoneal antiangiogenic agent plus chemotherapy. As explosive endpoints, we will examination the expression of VEGF-A in peritoneal cavity during the treatment.

Study Overview

• Status: Unknown
• Conditions: Peritoneal Adhesion
• Intervention / Treatment: Drug: Bevacizumab; Drug: Carboplatin; Drug: paclitaxel

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Nan Du, PhD; Email: dunan304@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100048
      • Recruiting
      • First Affiliated Hospital, Chinese PLA General Hospital
      • Contact: Hui Zhao, Phd
      • Principal Investigator: Nan Du, Phd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Pathologically and radiologically confirmed stage IV or postoperative recurrence ovarian cancer.
2. Age of 18-70, Karnofsky score higher than 80.
3. No severe functional damage of major organ, normal liver and kidney function.
4. Peritoneal adhesion. (1) peritoneal adhesions diagnosed by microlaparoscopy or abdominal operations, and classification according to Nair criteria is performed. (1) must be met. (2) Peritoneal adhesion symptoms, intermittent abdominal pain, abdominal distension, nausea and vomiting, hard to pass stools or gas; (3) Peritoneal adhesion signs，abdominal distension, abdominal tenderness, reduced or absent bowel sounds; (4) B ultrasound or CT or MRI show peritoneal adhesion or adhesion-related complications.

Exclusion Criteria:

1. Complete intestinal obstruction and suitable for surgery.
2. Patients known to be allergic to bevacizumab or any of the components of the drug.
3. Other ongoing anti-tumor treatment.
4. Heart disease with significant clinical symptoms, such as: congestive heart failure, coronary heart disease with symptom, arrhythmia hardly be controlled by drugs, myocardial infarction in 6 months, or heart failure

5. Active wound infection and a history of uncontrolled psychiatric illness.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intraperitoneal bevacizumab+ carboplatin; Intraperitoneal administration: intraperitoneal bevacizumab plus carboplatin every 3 weeks for 4-6 cycles Systemic chemotherapy: paclitaxel, iv. every 3 weeks for 4-6 cycles	Drug: Bevacizumab; Bevacizumab 5mg/kg intraperitoneal administration every 3 weeks for 4-6 cycles; Other Names: Avastin; Drug: Carboplatin; carboplatin AUC=5 intraperitoneal administration every 3 weeks 4-6 cycles; Drug: paclitaxel; paclitaxel 175mg/m2, iv d1, every 3 weeks for 4-6 cycles
ACTIVE_COMPARATOR: Intraperitoneal carboplatin; Intraperitoneal administration: intraperitoneal carboplatin every 3 weeks Systemic chemotherapy: paclitaxel, iv. every 3 weeks for 4-6 cycles	Drug: Carboplatin; carboplatin AUC=5 intraperitoneal administration every 3 weeks 4-6 cycles; Drug: paclitaxel; paclitaxel 175mg/m2, iv d1, every 3 weeks for 4-6 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peritoneal adhesion ORR (pORR)	Degree of adhesion was measured according to NAIR's criteria by laparoscopy. Grade 0 corresponded to no adhesions, Grade 1 and 2 corresponded to filmy adhesions and grade 3 and 4 to dense adhesions. No adhesions is defined as CR, dense adhesions change to filmy adhesions is defined as PR. The total efficiency ORR was calculated by taking the sum of CR+PR.	3weeks after the last treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients with Adverse Events	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	From first dose up to 1 month after the last treatment
Quality of Life (QoL)	Quality of Life (QoL) assessed by FACT-O	From first dose up to 1 year
Progression free survival (PFS)	From randomization until documented progressive disease or death	Up to 3 years
Overall survival (OS)	From randomization until death	Up to 3 years
Objective Response Rate (ORR)	The proportion of patients that have a best overall response of complete response (CR) or partial response (PR), as assessed by RECIST 1.1.	Up to 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression of VEGF-A in peritoneal cavity	Quantitation of VEGF-A by enzyme-linked immunosorbent assay (ELISA), before and after intraperitoneal administration.	Up to 1 year

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Investigators: Study Director: Nan Du, PhD, PLA 304 hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 1, 2017
• Primary Completion (ANTICIPATED): June 1, 2020
• Study Completion (ANTICIPATED): June 1, 2020

Study Registration Dates

• First Submitted: March 16, 2017
• First Submitted That Met QC Criteria: March 23, 2017
• First Posted (ACTUAL): March 29, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 13, 2017
• Last Update Submitted That Met QC Criteria: April 11, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: bevacizumab; Ovarian Cancer; Intraperitoneal administration; Peritoneal Adhesion
• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis; Cicatrix; Tissue Adhesions; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Carboplatin; Paclitaxel; Bevacizumab
• Other Study ID Numbers: Intraperitoneal bev

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes