Neoplasms

All Conditions

Symptoms and General Pathology

Wounds and Injuries

Digestive System Diseases

Carcinoma

Adenocarcinoma

Hyperthermia

Fever

Peritoneal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Fluorouracil

Albumin-Bound Paclitaxel

Cisplatin

Tubulin Modulators

Antimitotic Agents

5-FU

Two days prior to planned surgery, paclitaxel is infused IV over 24 hours.

Patients will undergo cytoreductive surgery, to debulk tumor. Scope of procedure will vary with each patient, including a spectrum of possible procedures, such as splenectomy, liver resection, pancreatic resection or bowel resection.

After cytoreductive surgery, continuous hyperthermic peritoneal perfusion (CHPP) surgery with cisplatin will begin by placing an influx and efflux catheters via abdominal wall. Perfusion rate of cisplatin is 1.5 L/min and the duration is 90 min.

Postoperative intraperitoneal chemotherapy will begin 24 hours after CHPP surgery.

Dose escalation will proceed after patients at a given dose level receive 3 courses. In order to properly evaluate hematoxicity, a minimum of 3 weeks will be required before dose escalation. MTD is either the dose level immediately below the level at which 2 of 6 patients in a cohort experience nonhematologic dose limiting toxicity (DLT) or when 4 of 6 patients experience hematologic DLT.

Two to 4 months after surgery, laparotomy will be conducted to determine response to treatment. If tumor size is decreased, patients will undergo a second treatment course identical to the same techniques and chemotherapy agents.

Peritoneal carcinomatosis is considered a terminal stage of tumor progression. Cytoreductive surgery plus aggressive combination intraperitoneal chemotherapy may significantly alter the natural history of this disease. This study will define the maximum tolerated dose of paclitaxel and 5-fluorouracil (5-FU) given as an early post-operative intraperitoneal (IP) dwell therapy after cytoreductive surgery and continuous hyperthermic peritoneal perfusion with cisplatin (CHPP).

Phase I Trial of Continuous Hyperthermic Peritoneal Perfusion (CHPP) With Cisplatin Plus Early Postoperative Intraperitoneal Paclitaxel and 5-FU for Peritoneal Carcinomatosis

National Cancer Institute (NCI)

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Colonic Neoplasms

Mesothelioma

Mesothelioma, Malignant

Adenoma

Neoplasms, Mesothelial

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Malignant Mesothelioma

Anti-Inflammatory Agents

Pharmaceutical Solutions

Anti-Allergic Agents

Antiemetics

Central Nervous System Depressants

Gastrointestinal Agents

Dermatologic Agents

Herbal and Botanical

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Diphenhydramine

Promethazine

Pancrelipase

Pancreatin

Ranitidine

Ranitidine bismuth citrate

Cola

Patients with peritoneal mesothelioma suffer with intractable ascites but have a very surface oriented tumor which usually does not invade into organs and cause organ dysfunction. The main source of symptoms and cause of death is intractable ascites.

Low grade mucinous adenocarcinoma also includes low grade mucinous neoplasms of borderline malignant potential. Patients with low grade mucinous adenocarcinoma can have prolonged survival with debulking surgery alone. The majority of patients with truly malignant disease will die of complications from intraperitoneal progression of tumor within 2 to 5 years. The tumors are often surface oriented within the peritoneal cavity without metastases to other distant sites. The most common origin for this type of tumor is the appendix and ovary.

Adenocarcinoma of gastrointestinal origin also includes other than low grade mucinous. Aggressive gastrointestinal adenocarcinomas such as gastric, small bowel, and colon cancer , tend to be more invasive into tissues and can more readily metastasize to distant sites. The cause of death is usually directly related to intraperitoneal progression of tumor. It is a more difficult group of patients to treat with intraperitoneal therapy because of the aggressive and invasive nature of the tumors.

Patients will undergo cytoreductive surgery to remove as much tumor as possible. Part of the intestines, pancreas, stomach or the entire spleen may also be removed if they are affected.

Surgery

Continuous hyperthermic peritoneal perfusion (CHPP) with Cisplatin

Intraperitoneal dwell chemotherapy with a combination of 5-FU and Paclitaxel will be delivered in the early postoperative period (day 7 today 12 after surgery). Patients will be premedicated with hydrocortisone (100 mg/intravenous push (i.v.p.)), diphenhydramine (50 mg i.v.p.) and ranitidine (50 mg i.v.p.) 30 minutes prior to delivering intraperitoneal chemotherapy. One liter of normal saline will be infused containing 5-FU (800 mg/M\^2) and 1 L of normal saline containing paclitaxel (125 mg/M\^2) will be infused over 60 minutes. The chemotherapy solution will be left in the abdominal cavity permanently for slow absorption.

Postoperative dwell with paclitaxel and 5-FU

Marybeth S Hughes, M.D.

This study will test the effectiveness of an experimental treatment for peritoneal cancer involving surgical removal of the tumor, perfusion of the abdomen during surgery with a heated solution of the drug cisplatin, and post-surgery combination chemotherapy in the abdomen with fluorouracil (5-FU) and paclitaxel.

Patients with certain peritoneal cancer whose tumors are confined to the abdomen may be eligible for this study. Candidates are screened with a medical history and physical examination, including blood tests, electrocardiogram and possibly bone scan, brain magnetic resonance imaging (MRI), and chest, abdomen and pelvic CT scans.

Participants undergo surgery to remove as much tumor as possible. Part of the intestines, pancreas, stomach or the entire spleen may also be removed if they are affected. During surgery, after the tumor has been removed, two catheters (thin plastic tubes) are placed in the abdomen. A chemotherapy solution containing the anti-cancer drug cisplatin heated to a temperature of about 108.6 degrees (10 degrees above normal body temperature) is then delivered into the abdomen through one catheter and drained through another. During treatment, a drug called sodium thiosulfate is given through a vein to reduce the risk of side effects of cisplatin, particularly kidney damage. After 90 minutes of bathing the abdomen with this solution, the drug is rinsed from the abdomen and the catheters removed. Another small catheter is then placed and left inside the abdomen with one end coming out through the skin. Seven to 12 days after the operation, the anti-cancer drugs 5-FU and paclitaxel are given through this catheter.

After complete recovery from the surgery, the catheter is removed and the patient is discharged from the hospital. Clinic visits are scheduled for periodic follow-up examination, imaging, and tests 3 and 6 months after surgery and every 6 months for up to 5 years as long as the disease does not worsen. Patients whose disease progresses are taken off the study and referred back to their local physician or referred for alternative care or other research studies.

Patients are also asked to assess how this therapy affects their general health and well being. This will require filling out two quality-of-life (QOL) questionnaires before surgery and again at each follow-up visit after surgery. Each questionnaire takes about 15 minutes to complete.

Background:

Cytoreductive surgery plus aggressive combination intraperitoneal chemotherapy may significantly alter the natural history of peritoneal carcinomatosis. The purpose of this study is to examine the treatment results of continuous hyperthermic peritoneal perfusion (CHPP) with cisplatin plus early postoperative intraperitoneal dwell therapy with 5-FU and paclitaxel after cytoreductive surgery for peritoneal carcinomatosis.

Objectives:

The primary objective of this study is to determine response and survival after continuous hyperthermic peritoneal perfusion with cisplatin and early postoperative intraperitoneal dwell therapy with 5-FU and paclitaxel. Response can only be assessed by measuring the time to clinical or radiographic recurrence of disease.

The secondary objectives include the determination of pharmacokinetics of paclitaxel and 5-FU delivered into the peritoneal cavity and the impact that continuous hyperthermic peritoneal perfusion with cisplatin and early postoperative intraperitoneal dwell therapy with 5-FU and paclitaxel has on patients' health related quality of life.

The evaluation of pure populations of tumor and normal mesothelial cells to

* determine if signal transduction pathways are distinct in tumor versus normal tissue
* to see if specific cell pathways are activated or inhibited as a consequence of therapy.
* to validate that this technology can provide informative data about these events as a potential surrogate for clinical benefit from therapy or biological behavior of the tumor.

Eligibility:

The patient greater than or equal to 30 kg must have histologically proven peritoneal carcinomatosis from one of the following histologies: 1) primary peritoneal mesothelioma; 2) low grade mucinous adenocarcinoma (including low grade mucinous neoplasms of borderline malignant potential); 3) adenocarcinoma of gastrointestinal tract origin (other than low grade mucinous, excluding pancreatic cancer), with disease confined to the peritoneal cavity. Patients may not have had treatment for their disease within the previous 30 days and have recovered from all toxicity. Patients must meet certain safety laboratory criteria and may not have major medical disorders that would place them at unacceptable risk for a major surgical procedure. Patients may not have received prior intraperitoneal platinum therapy.

Design:

Patients will undergo cytoreductive surgery followed by CHPP with cisplatin. A peritoneal dialysis catheter will be inserted into the peritoneal cavity at the time of laparotomy. In the early postoperative period (day 2 - 10) intraperitoneal dwell chemotherapy with paclitaxel (125 mg/M\^2) and 5-FU (800 mg/M\^2) will be administered. Patients will be seen 4 - 6 weeks after discharge for a physical examination and laboratory screen and QOL evaluation. Tumor marker will be included at this stage. Patients will then be seen every 3 months for the first year after surgery and every 6 months thereafter. At each visit they will undergo physical examination, laboratory screening (including tumor marker) and a CT scan of the chest, abdomen and pelvis and QOL evaluation.

The objective of this pilot study is to estimate the ability of peritoneal perfusion to achieve potentially tolerable disease free survival in patients with a variety of tumors. For each class of tumors, an appropriate, distinct median disease free survival will be targeted as the principal endpoint. The trial will be conducted as a set of three single-stage phase II studies, with an early stopping rule for clearly unacceptable outcomes. It is expected that accrual for 59 patients with adenocarcinoma of gastrointestinal origin (other than low grade mucinous), 48 patients with low grade mucinous adenocarcinoma, and 96 patients with primary peritoneal mesothelioma (total accrual of 203) will require approximately 5 -6 years.

Results will be assessed by following the time to radiographic or clinical recurrence of disease and survival. Patients will be stratified for entry based on histology. This will include 3 cohorts: 1) peritoneal mesothelioma; 2) low grade mucinous adenocarcinoma (including low grade mucinous neoplasms of borderline malignant potential); and 3) adenocarcinoma of gastrointestinal origin (other than low grade mucinous).

Treatment of Peritoneal Cancer With Surgery, Perfused Heated Cisplatin and Chemotherapy

Phase II Trial of Continuous Hyperthermic Peritoneal Perfusion (CHPP) With Cisplatin Plus Early Postoperative Intraperitoneal Paclitaxel and 5-Fluorouracil for Peritoneal Carcinomatosis

Participants who achieve either a six or twelve month disease free interval based on radiographic imaging and symptoms.

Response is assessed by measuring the time to clinical or radiographic recurrence of disease. Patients will be followed with computed tomography (CT) scans. At any time point where there is evidence of progressive disease in the peritoneal cavity (imageable tumor nodules or new onset of ascites) the patients will be scored as failing within the abdominal cavity.

Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

Paclitaxel and 5-FU levels in plasma and perfusate will be determined by standard high-performance liquid chromatography (HPLC). Samples will be collected just prior to (Time 0) the infusion of the intraperitoneal dwell of 5-FU and paclitaxel, at the following time intervals after the conclusion of the intraperitoneal dwell infusion (15 minutes, 1 hour, 6 hour, 12 hour, 24 hour, 48 hour).

The Short-Form-36 Health Survey (SF-36) and the Functional Assessment of Cancer Therapy Disease Specific for Colorectal Cancer (FACT-C) will be given to the patients upon admission preoperatively, then 6 weeks postoperatively, and then 3, 6, 9, and 12 months for the first year and then every 6 months until the patient goes off study. These forms summarize a participants positive and negative aspects that characterize one's psychological (emotional(, physical, and social well-being at a point in time.

For detailed information about the questionnaires, please see the Protocol Link module.

Signal transduction pathways were measured using reverse phase protein lysate microarray to determine if the pathways are distinct in tumor versus normal tissue.

Principal Investigator

Adverse Events: 188 participants is consistent with the total number of participants analyzed (e.g. total from each column in participant flow, 83 P.Meso + 48 L.Grade + 57 Adeno. = 188).

Patients with peritoneal mesothelioma suffer with intractable ascites. Patients with low grade mucinous adenocarcinoma can have prolonged survival with debulking surgery alone. Adenocarcinoma of gastrointestinal origin also includes other than low grade mucinous. Aggressive gastrointestinal adenocarcinomas such as gastric, small bowel, and colon cancer, tend to be more invasive.

Mesothelioma, Low Grade, and Adenocarcinoma

Peritoneal Mesothelioma

Low Grade Mucinous Adenocarcinoma

Adenocarcinoma of Gastrointestinal Origin

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

White

Hispanic

African American

Asian American

Unknown

Race/Ethnicity, Customized

United States

Region of Enrollment

Marybeth S. Hughes, M.D.

This outcome measure was not analyzed because information was not consistently available.

Number of Participants With Disease-free Survival

Number of Participants With a Response

188 participants is consistent with the total number of participants analyzed (e.g. total from each column in participant flow, 83 P. Meso + 48 L. Grade + 57 Adeno. = 188).

Number of Participants With Adverse Events

This outcome measure was not analyzed because it was not feasible (e.g. inadequate samples).

Percentage of Participants Who Had Paclitaxel and 5-fluorouracil (5-FU) Analysis Performed

This outcome measure was not evaluated due to poor patient compliance.

Quality of Life Questionnaire Score

Normal Tissue

Tumor Tissue

This outcome measure was not analyzed because it was not feasible.

Signal Transduction Pathways in Tumor Tissue Versus Normal Tissue

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

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

Fallopian Tube Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Carboplatin

Angiogenesis Inhibitors

Semaxinib

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

SU5416 and carboplatin

SU5416, a novel antiangiogenesis agent, has been shown to be a potent and selective inhibitor of the tyrosine kinase activity of FlK-1 (a downstream effector of VEGF) in vitro and to inhibit the growth of endothelial cells. Since VEGF mRNA levels and vessel counts in tumor tissues have been shown to be inversely related to prognosis in ovarian cancer, SU5416 may prove to be a useful agent in this disease. Platinum agents currently provide the most effective treatment for ovarian cancer. However, ovarian cancer often becomes refractory to platinum therapy, leaving the patient with a poor prognosis. This is a phase I study designed to: a) determine a dose level of carboplatin to use in combination with an established dose of SU5416 for treatment of patients with platinum-refractory ovarian cancer, b) assess the side effect profile of SU5416 and carboplatin combination therapy, c) characterize any alterations in SU5416 pharmacokinetic and pharmacodynamic parameters when given in combination with carboplatin, d) characterize carboplatin pharmacokinetic and pharmacodynamic parameters when given in combination with SU5416, e) do exploratory studies to assess the effect of SU5416 on platinum-DNA adduct levels, f) do exploratory studies to assess any alterations in ERCC1 mRNA levels when carboplatin is administered with SU5416, and g) obtain preliminary evidence of the ability of SU5416 to reverse platinum resistance in patients with platinum-refractory ovarian carcinoma.

SU5416 and Carboplatin to Treat Ovarian Cancer

A Phase I Study of SU5416, an Antiangiogenesis Agent, in Combination With Carboplatin in Patients With Platinum-Refractory Ovarian Cancer

Enzastaurin: 1125 milligram (mg) loading dose then 500 mg oral tablet, daily for six 21-day cycles or up to 3 years

Carboplatin: Area under the concentration time curve (AUC) 5 intravenous (IV), every (q) 21 days for six 21-day cycles

Paclitaxel:175 milligrams/square meter (mg/m²) IV, q21 days for six 21-day cycles

Carboplatin: AUC5 IV, q21 days for six 21-day cycles

Paclitaxel: 175 mg/m², IV, q21 days for six 21-day cycles

Placebo: oral tablet

enzastaurin

carboplatin

paclitaxel

placebo

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Participants with ovarian cancer usually get the drugs carboplatin and paclitaxel as initial treatment. In many participants the tumor will shrink, or even disappear, after treatment with these drugs. But, unfortunately, the tumor will grow again in many participants. This trial will try to address the question: Can we delay the time till the tumor grows again by adding a 3rd drug to the standard therapy? To answer this question, participants will, by chance, either get the experimental drug enzastaurin or a "dummy pill" (placebo) during the chemotherapy and for up to 3 years after chemotherapy. Participants and physicians will not know if a participant gets enzastaurin or placebo (double-blinded trial). After a predefined time, the treatment will be uncovered, and the number of participants with tumor growth at a specific time point will be compared between the two treatments.

Comparing Two Treatments for Ovarian Cancer: Standard Chemotherapy Plus Enzastaurin, or Placebo ("Sugar Pill")

A Randomized, Phase 2, Placebo-Controlled, Double-Blinded Study With and Without Enzastaurin in Combination With Paclitaxel and Carboplatin as First-Line Treatment, Followed by Maintenance Treatment in Advanced Ovarian Cancer

PFS was defined as time from date of randomization to first date of determined progressive disease (PD) or death from any cause. PD defined using Response Evaluation Criteria in Solid Tumors (RECIST v1.0) and Gynecological Cancer Intergroup (GCIG) criteria. RECIST: ≥20% increase in sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since treatment started or appearance of ≥ 1new lesions and/or unequivocal progression of existing non-target lesions. GCIG: Cancer Antigen-125 (CA-125) serum ≥2 times upper limit of normal (ULN) for those in normal range or nadir for participants who never achieved normal range. Participants not known to have died and did not have PD were censored at last progression-free assessment. Those who received subsequent systemic anticancer therapy (after study drug discontinued) prior to determined PD or death, were censored at date of last progression-free disease assessment prior to post-discontinuation chemotherapy.

PFS was defined as time from date of randomization to first date of determined PD or death from any cause. PD defined using RECIST v1.0 and GCIG criteria. RECIST v1.0: as ≥20% increase in sum of LD of target lesions taking as reference the smallest sum LD recorded since treatment started or appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. GCIG: CA-125 serum ≥2 times ULN for those in normal range or nadir (the lowest value of blood counts after chemotherapy) for participants who never achieved normal range. Participants not known to have died and did not have PD were censored at last progression-free assessment. Those who received subsequent systemic anticancer therapy (after study drug discontinued) prior to determined PD or death, were censored at date of last progression-free disease assessment prior to post-discontinuation chemotherapy.

ORR was the percentage of participants with a CR or PR using RECIST v1.0 and CA-125 GCIG criteria. RECIST v1.0: CR was defined as the disappearance of all tumors. PR was defined ≥30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD or complete disappearance of target lesions, with persistence (but not worsening) of ≥1 nontarget lesions and appearance of no new lesions. GCIG: CA-125 serum ≥2 times above ULN for those in normal range or nadir for participants who never achieved normal range. ORR calculated as: (CR + PR) / (total number of participants qualified for tumor response analysis per arm) \* 100.

Rate of response was defined using RECIST v1.0 and CA-125 GCIG criteria. RECIST v1.0: CR was defined as the disappearance of all target lesions. PR was defined ≥30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD or complete disappearance of target lesions, with persistence (but not worsening) of ≥1 nontarget lesions and appearance of no new lesions. SD was defined as small changes that did not meet the above criteria. PD was defined as having a ≥20% increase in the sum of the LD of target lesions. GCIG: CA-125 serum ≥2 times above ULN for those in normal range or nadir for participants who never achieved normal range. Rate of response calculated as: (CR + PR + SD)/(total number of participants qualified for tumor response analysis per arm) \*100.

PE measured using Immunohistochemistry (IHC) assay, scored 0 (negative, no staining) to 3+ (brightest staining). IHC H-scores for protein biomarkers (PKCβ2, PTEN, pCREB, pGSK3b, pS6) calculated as: \[1\*(percentage of cells stained \[PCS\] as 1+)\]+\[2\*(PCS as 2+)\]+\[3\*(PCS as 3+)\]. High PE: ≥marker threshold value and Low PE: \<marker threshold value. PFS: date of randomization to PD or death. PD defined using RECIST v1.0 and GCIG criteria. RECIST: ≥20% increase in sum of LD of target lesions taking as references smallest sum LD recorded since treatment started or appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. GCIG: CA-125 serum ≥2 times ULN for those in normal range or nadir for those who never achieved normal range. Per protocol, Part 1 was not included as it is an open-label safety lead-in portion with PK characterization.

Clinically significant events were defined as SAEs and other non-serious AEs regardless of causality. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. The number of participants SAEs, other non-serious AEs, and those who died due to PD are included.

Cmax,ss for enzastaurin, its metabolite LSN326020 (LY326020) and total analytes are reported.

AUCτ,ss for enzastaurin, its metabolite LSN326020 (LY326020), and total analytes are reported.

Eli Lilly and Company

Enzastaurin: 1125 mg loading dose on Cycle 1 Day 4, then 500 mg oral tablet, QD, for six 21-day cycles on subsequent days of chemotherapy

Carboplatin: AUC5, IV, q21 days, for six 21-day cycles

Paclitaxel: 175 mg/m² IV, q21 days, for six 21-day cycles

Part 1 - Modified Regimen A

Enzastaurin: 1125 mg loading dose then 500 mg, oral tablets on subsequent days, QD, for six 21-day cycles or up to 2 years

Carboplatin: AUC5, IV, q 21 days, for six 21-day cycles

Paclitaxel: 175 mg/m², IV, q21 days, for six 21-day cycles

Part 2 - Regimen A

Carboplatin: AUC5, IV, q21 days, for six 21-day cycles

Paclitaxel: 175 mg/m2² IV, q 21 days, six 21 day cycles

Placebo: oral tablet, QD

Part 2 - Regimen B

Enzastaurin: 1125 mg loading dose on Cycle 1 Day 4 then 500 mg oral tablet, QD, for six 21-day cycles on subsequent days of chemotherapy

Carboplatin: AUC5, IV, q21 days, for six 21-day cycles of chemotherapy

Paclitaxel: 175 mg/m², IV, q21 days, for six 21-day cycles of chemotherapy

Enzastaurin: 1125 mg loading dose then 500 mg oral tablet, QD, for up to six 21-day cycles on subsequent days of chemotherapy and maintenance therapy up to 2 years

Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy

Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy

Carboplatin: AUC5 IV, q21 days, for up to six 21-day cycles of chemotherapy

Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy

Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years

Caucasian

East Asian

West Asian (Indian sub-continent)

Belgium

Poland

Spain

Russia

Germany

Part 1: All enrolled participants Part 2: All randomized participants

All of the percentages do not add up to 100% because of rounding.

Chief Medical Officer

All randomized participants from Part 2 group. Participants censored for Part 2: Regimen A=38, Regimen B=35. Per protocol, Part 1 was not included as it is an open-label safety lead-in portion with PK characterization.

Part 2: Progression-Free Survival (PFS)

Carboplatin: AUC5, IV, q21 days, for up to six 21-day cycles of chemotherapy

Paclitaxel: 175 mg/m², IV, q21 days, for up to six 21-day cycles of chemotherapy

Placebo: oral tablet, QD, of chemotherapy and maintenance therapy up to 2 years

Part 2: Percentage of Participants With PFS at 2 Years

All randomized participants from Part 2 group, who were evaluated for tumor response. Per protocol, Part 1 was not included as it is an open-label safety lead-in portion with PK characterization.

Part 2: Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]

All randomized participants from Part 2 group, who qualified for tumor response analysis. Per protocol, Part 1 was not included as it is an open-label safety lead-in portion with PK characterization.

Part 2: Percentage of Participants With CR or PR or Stable Disease (SD) (Rate of Response)

PKCβ2 Cytoplasm High Expression (H≥115)

PKCβ2 Cytoplasm Low Expression (H<115)

All randomized participants (Pts) from Part 2 group. Pts censored: Regimens A/B (A/B)-High (H), Low (L) Expression: PKCβ2 Cytoplasm (Cyto) (H4/5,L26/22), PTEN Cyto (H24/24, L6/3), PTEN Membrane (H9/8, L21/19), PTEN Nucleus (H13/6, L17/21), pCREB Nucleus (H14/10, L16/17), pGSK3b Cyto (H7/3, L22/23), pS6 Cyto (H21/18, L9/9).

Part 2: Translational Research: PFS Based on Protein Expression (PE) (To Assess Biological Markers in Tumors That Could Indicate Who Could Benefit From Enzastaurin Treatment)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I Trial of Continuous Hyperthermic Peritoneal Perfusion (CHPP) With Cisplatin Plus Early Postoperative Intraperitoneal Paclitaxel and 5-FU for Peritoneal Carcinomatosis	NCT00001569	Carcinoma Peritoneal Neop...	Cisplatin Paclitaxel 5-FU	-	National Institutes of Health Clinical Center (CC)
Treatment of Peritoneal Cancer With Surgery, Perfused Heated Cisplatin and Chemotherapy	NCT00004547	Abdominal Neopl... Colonic Neoplas... Mesothelioma Peritoneal Neop...	Surgery Continuous hype... Postoperative d...	18 Years -	National Institutes of Health Clinical Center (CC)
SU5416 and Carboplatin to Treat Ovarian Cancer	NCT00006155	Fallopian Tube ... Ovarian Cancer Peritoneal Neop...	SU5416 and carb...	-	National Institutes of Health Clinical Center (CC)
Phase I Trial of Continuous Hyperthermic Peritoneal Perfusion (CHPP) With Cisplatin Plus Early Postoperative Intraperitoneal Paclitaxel and 5-FU for Peritoneal Carcinomatosis	NCT00001569	Carcinoma Peritoneal Neop...	Cisplatin Paclitaxel 5-FU	-	National Institutes of Health Clinical Center (CC)
SU5416 and Carboplatin to Treat Ovarian Cancer	NCT00006155	Fallopian Tube ... Ovarian Cancer Peritoneal Neop...	SU5416 and carb...	-	National Institutes of Health Clinical Center (CC)
Comparing Two Treatments for Ovarian Cancer: Standard Chemotherapy Plus Enzastaurin, or Placebo ("Sugar Pill")	NCT00391118	Ovarian Cancer Fallopian Tube ... Peritoneal Neop...	enzastaurin carboplatin paclitaxel placebo	18 Years -	Eli Lilly and Company

Spots Global Cancer Trial Database for peritoneal neoplasm