New Trials


Study

Type of study

Phase

Time

Drug

Id number*

Country

Feasibility Study of HIPEC for Patients With Stage III or Only Pleural Stage IV Ovarian Carcinoma in First-Line Therapy

Safety/efficacy

II–III

Primary

Cisplatin

NCT01709487

Belgium

Phase 3 Trial Evaluating Hyperthermic Intra-peritoneal Chemotherapy in Upfront Treatment of Stage IIIC Epithelial Ovarian Cancer (CHORINE)

Randomized

III

Primary

Cisplatin + paclitaxel

NCT01628380

Italy

Quality of Life and Survivorship Care in Patients Undergoing Hyperthermic Intraperitoneal Chemotherapy (HIPEC) (HOPE)

Efficacy

n.p.

Primary recurrence
 
NCT01126346

USA

Surgery and Chemotherapy With or Without Chemotherapy After Surgery in Treating Patients With Ovarian, Fallopian Tube, Uterine, or Peritoneal Cancer

Safety

n.p.

Primary recurrence

Cisplatin, carboplatin, PLDH, Paclitaxel, gentamicin

NCT01970722

USA

Intraoperative Hyperthermic Intraperitoneal Chemotherapy With Ovarian Cancer

Randomized

III

Primary recurrence

Cisplatin

NCT01091636

Korea

Safety and Pharmacokinetics of Intraoperative Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) With Cisplatin to Treat Platinum-sensitive Recurrent Ovarian Cancer

Nonrandomized

I

Recurrence

Cisplatin

NCT01387399

Germany

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Ovarian Cancer Recurrence (HORSE)

Randomized

III

Recurrence

Cisplatin

NCT01539785

Italy

Outcomes After Secondary Cytoreductive Surgery With or Without Carboplatin Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Followed by Systemic Combination Chemotherapy for Recurrent Platinum- Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Randomized

II

Recurrence

Carboplatin

NCT01767675

USA

A Phase II Combined Modality Protocol of Debulking Surgery With HIPEC Followed by Intraperitoneal Chemotherapy for the Treatment of Recurrent Ovarian, Primary Peritoneal and Fallopian Tube Cancers

Safety/efficacy

II

Recurrence

Cisplatin

NCT01659554

USA

Secondary Debulking Surgery ± Hyperthermic Intraperitoneal Chemotherapy in Stage III Ovarian Cancer (OVHIPEC)

Randomized

III

Recurrence

Cisplatin

NCT00426257

Netherlands

Hyperthermic Intra-Peritoneal Chemotherapy (HIPEC) in Relapse Ovarian Cancer Treatment (CHIPOR)

Randomized

III

Recurrence

Cisplatin

NCT01376752

France

Carboplatin, Paclitaxel and Gemcitabine With or Without Bevacizumab After Surgery in Treating Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer

Randomized

III

Recurrence

Carboplatin, paclitaxel, gemcitabine, bevacizumab

NCT00565851

USA


*From www.clinicaltrials.gov; n.p., not provided





25.8 New Trials in Gastric Cancer


Regarding the treatment of GC, a recent French protocol is ongoing: Glehen et al. [11] stress the importance of validating HIPEC efficacy in European and Caucasian patients with IP recurrence from GC, as was previously done in Asian patients [11]. The objective of the D2 Resection and HIPEC (Hyperthermic Intraperitoneal Chemoperfusion) in Locally Advanced Gastric Carcinoma (GASTRICHIP) prospective, open, randomized, multicenter, phase III clinical study is to evaluate the effects of HIPEC with oxaliplatin 250 mg/m2 at 42–43°C for 30 min.

Research is focusing on new drugs with different targets. Recent studies analyzed the importance of vascular endothelial growth factor (VEGF) in malignant ascites to improve peritoneal liquid production and neoangiogenesis [47, 48]. In EOC, bevacizumab IV was tested. The only indication for this treatment is in patients with advanced OC with poor prognostic indicators (stage IV or suboptimal debulking) [49]. Nevertheless, trials with other antiangiogenic drugs are ongoing. Their use has also been studied in HIPEC. The Lyon group, in a recent randomized phase II study [47] of patients with malignant ascites from GC with synchronous PC, obtained a clinical effect after IP infusion of catumaxomab—a nonhumanized chimeric antibody that blocks epithelial-cell adhesion molecule (EpCAM), T lymphocyte, CD3, accessory-cell, and Fcγ receptors. Indeed, in GC, this molecule is expressed in 90 % of cases, and IP infusion of catumaxomab could efficiently treat microscopic residual disease after CRS.

The aim of a US safety/efficacy study [50] is to determine the safety of a laparoscopic approach for HIPEC administration. Primary outcome is OS; secondary outcomes are safety and toxicity. The study arm receives mitomycin-C and cisplatin for 1 h on day 1 through three or four small abdominal incisions. After IP chemotherapy, the liquid is removed and a peritoneal washing and, eventually, biopsies are performed. Patients receive sodium thiosulfate IV to protect the kidneys.

Another ongoing US study [51] is evaluating technical parameters (CRS CC, achievement of hyperthermia, and morbidity and mortality rates) in patients with PC from CRC, GC, appendiceal, pseudomyxoma peritonei (PMP), and malignant peritoneal mesothelioma (MPM) origin undergoing CRS plus HIPEC with mitomycin-C (40 mg for 90 min).

The aim of a Spanish nonrandomized multicentric phase II study [52] is 1C level of evidence in terms of DFS and OS in patients with PC from GC. The strategy is to validate two new treatment schemas in three phases: In phase I, patients undergo IP infusion (through a peritoneal catheter implant) of docetaxel (30 mg/m2) and cisplatin (30 mg/m2) and IV administration of 5-FU (200 mg/m2/day, 7 days/week for 2 weeks) simultaneously with two cycles of IP administration. Phase II involves CRS plus HIPEC (mitomycin-C 15 mg/m2 plus Adriamycin 15 mg/m2 at 42–43°C for 60 min) and simultaneous IV administration of 5-FU (400 mg/m2) plus leucovorin (20 mg/m2) for 10 min at the beginning of peritoneal perfusion. In the phase III, adjuvant chemotherapy with docetaxel (75 mg/m2), cisplatin (75mg/m2), and 5-FU (750mg/m2 day) is administered 8–12 weeks after surgery.

A German RCT study [53] compared patients with GC with IP free tumor cells (≥ T2, < T4, M0, N±) in two arms: in the experimental arm, HIPEC with mitomycin-C and cisplatin was administered after gastrectomy. In the control group, surgery only was performed. The primary outcome is PC-free survival at 5 years; the seconds is DFS at 5 years. A Chinese trial [54] is comparing different chemotherapy regimens with oxaliplatin and paclitaxel in HIPEC from GC to evaluate OS as primary outcome and safety and adverse events.

Table 25.2 summarizes new trials for treating GC.


Table 25.2
Ongoing clinical trial on HIPEC in gastric cancer




























































Study

Type of study

Phase

Drug

ID number*

Country

D2 Resection and HIPEC (Hyperthermic Intraperitoneal Chemoperfusion) in Locally Advanced Gastric Carcinoma (GASTRICHIP)

Randomized

III

Oxaliplatin

NCT01882933

France

Laparoscopic Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) for Metastatic Gastric Cancer

Safety/efficacy

II

Mitomycin-C, cisplatin

NCT02092298

USA

Single-Arm Study Treating Patients of Peritoneal Surface Malignancy (Colorectal, Appendical, Pseudomyxoma, Gastric) With Cytoreductive Surgery and Hyperthermic Intraperitoneal Mitomycin C

Safety/efficacy

II

Mitomycin-C

NCT02040142

USA

Clinical Trial at Neoadjuvant Peritoneal and Systemic Chemotherapy Plus HIPEC in Gastric Carcinomatosis

Safety/efficacy

II

Docetaxel, cisplatin, mitomycin-C, Adriamycin, leucovorin Mitomycin-C

NCT01342653

Spain

Randomized Controlled Trial to Prevent Peritoneal Seeding in Gastric Cancer cisplatin (HIPEC Stomach)

Randomized

II–III

Mitomycin-C, cisplatin

NCT01683864

Germany

Sequential HIPEC of Oxaliplatin and Paclitaxel for Gastric Cancer Patients With Peritoneum Metastasis (SHOP-G01)

Safety

II

Oxaliplatin, paclitaxel

NCT01471132

China


*From www.clinicaltrials.gov


25.9 New Trials in Colorectal Cancer


Ongoing is a US randomized phase II trial [55], the first study comparing EPIC vs. HIPEC for CRC and appendiceal cancer after CRS (< 2.5 mm). Drug regimens used during HIPEC and EPIC are mitomycin-C for the first one and floxuridine and leucovorin for the second one. Primary outcome is DFS at 3 years. A French multicenter phase III randomized trial [56] compares follow-up with explorative laparotomy plus HIPEC to simple follow-up in patients with CRC initially treated with surgery and adjuvant chemotherapy and are at high risk of developing PC. After the first tumor resection, patients undergo adjuvant treatment [6 months with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX-4) regimen]. If the recurrence risk is low, the patient is not randomized; if it is high, the patient will be randomized to surveillance alone (control group) or exploratory laparotomy plus HIPEC (experimental group).

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Mar 14, 2018 | Posted by in ONCOLOGY | Comments Off on New Trials

Full access? Get Clinical Tree

Get Clinical Tree app for offline access