Neoplasms

Digestive System Diseases

All Conditions

Gland and Hormone Related Diseases

Rectal Neoplasms

Colonic Neoplasms

Endocrine Gland Neoplasms

Appendiceal Neoplasms

Endocrine System Diseases

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Cecal Neoplasms

Cecal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

Oxaliplatin

Topoisomerase I Inhibitors

Enzyme Inhibitors

Oxaliplatin and irinotecan

Dominique Elias, MD

The purpose of this study is to evaluate the treatment of a cancerous disease of the peritoneum with complete cytoreductive surgery with intraperitoneal chemohyperthermia using oxaliplatin plus irinotecan.

This is a Phase II study with 100 patients. Origins of the tumors: these include colon, rectum, appendix, peritoneum, and endocrine tumors.

Treatment of a Cancerous Disease of the Peritoneum With Complete Cytoreductive Surgery and Intraperitoneal Chemohyperthermia

Treatment of a Cancerous Disease of the Peritoneum With Complete Cytoreductive Surgery With Intraperitoneal Chemohyperthermia Using Oxaliplatin Plus Irinotecan

Gustave Roussy, Cancer Campus, Grand Paris

Symptoms and General Pathology

Carcinoma

Adenocarcinoma

Neoplasm Metastasis

Colorectal Neoplasms

Liver Neoplasms

Colonic Diseases

Rectal Diseases

Liver Diseases

Hematinics

Herbal and Botanical

Liver Extracts

Cola

Stage 1: Four escalating dose cohorts of NV1020 3x10\^6 pfu, 1x10\^7 pfu, 3x10\^7 pfu, and 1x10\^8 pfu administered via hepatic artery infusion, over 10 minutes and repeated every 1-2 weeks for 4-8 weeks followed by 2 cycles of chemotherapy.

Stage 2: Expansion of one dose cohort from Stage 1 of optimal NV1020 dose administered via hepatic artery infusion, over 10 minutes and repeated every 1-2 weeks for 4-8 weeks followed by 2 cycles of chemotherapy.

NV1020 dose levels: 3x10\^6, 1x10\^7, 3x10\^7, and 1x10\^8 plaque forming units, administered via hepatic artery infusion, over 10 minutes and repeated every 1-2 weeks for 4-8 weeks

NV1020

Hoda Tawfik, PhD

This study is an open-label study. It has two stages. Stage 1 is a dose escalation phase of the study to determine and evaluate the safety and tolerability of repeated treatments with a genetically engineered herpes simplex virus NV1020 administered locoregionally to the liver.

Stage 2 is to evaluate the dose found in Stage 1 to be "optimally tolerated". Stage 2 is to assess the efficacy of the optimally tolerated dose of NV1020 by itself and in combination with second-line chemotherapy.

Assignment to Stage 1 or Stage 2 of the study is determined by when the patient enters the study.

This study is designed to evaluate the effects of repeated treatments with NV1020, prior to second-line chemotherapy, and to determine an appropriate dose level of NV1020 in a multiple dose regimen for later Phase II studies.

Sequential, open-label cohort dose escalation of NV1020 (stage 1) followed by an expansion of one selected dose cohort (stage 2).

Study results will be reviewed periodically by an independent DSMB who will approve each cohort dose escalation.

During the dose escalation stage, 3 cohorts of patients (3 in each) will be treated with 4 fixed doses of NV1020, with the dose level increasing for successive cohorts. A patient will be observed for a minimum of 7 days after the first NV1020 infusion before the next patient in the same cohort is given NV1020. The first patient in the next higher dose cohort will receive NV1020 no earlier than 14 days after the last patient in the prior cohort has finished NV1020 infusions. One additional cohort (half log higher increment) may be approved by the DSMB, if considered necessary to define MTD. Dose-limiting toxicity will be determined using NCI CTC criteria and a suitable dose level for later evaluation will be selected.

In the second stage of the study, the dose cohort considered to show the best therapeutic index will be expanded by the addition of 18 further patients. For all patients in this study, investigational treatment with NV1020 will be followed by a minimum of two cycles of second-line therapy using anti-neoplastic drugs approved by the FDA for colorectal cancer and selected by the investigator.

All patients will be followed up periodically until death. Permission for autopsy will be sought.

Safety & Efficacy of NV1020 in Colorectal Cancer Metastatic to the Liver

A Phase I/II, Open-label Study to Evaluate the Safety and Anti-tumor Effects of NV1020 Administered Repeatedly Via Hepatic Artery Infusion Prior to Second-line Chemotherapy, in Patients With Colorectal Adenocarcinoma Metastatic to the Liver

Incidence of adverse events for all patients (N=32); Overall incidence ≥20%; Adverse events listed by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term

Number of patients with NV1020 detected in saliva, skin, and/or mucosal surfaces; Analysis by polymerase chain reaction (PCR)

Number of patients with clinically significant hematology laboratory abnormalities by NV1020 dose cohort (Post baseline)

Number of patients with post-baseline clinically significant laboratory chemistry abnormalities by NV1020 dose cohort

Number of patients with post-baseline clinically significant laboratory coagulation abnormalities by NV1020 dose cohort

Maximum percentage changes in tumor diameter after administration of NV1020 followed by chemotherapy as measured by CT scan and Modified Response Evaluation Criteria in Solid Tumors (RECIST) assessment

Mean change from baseline in NV1020 neutralizing antibody titer by dose cohort

Progression assessed from CT and PET measurements and is determined as an increase of greater than or equal to 25% in the sum of the products of perpendicular diameters of all tumors, or the appearance of any new lesion.

Median change from baseline of Interferon (INF) gamma 8 hours post NV1020 infusion (Visits 1, 3, 5, 7)

Median change from baseline of Interleukin-6 (IL-6) 8 hours post NV1020 infusion (Visits 1, 3, 5, 7)

Median change from baseline of tumor necrosis factor (TNF-alpha) 8 hours post NV1020 infusion (Visits 1, 3, 5, 7)

MediGene

\*Serious adverse events exclude those which were deemed to be unrelated to NV1020

Escalating doses of NV1020: 3x10\^6, 1x10\^7, 3x10\^7, 1x10\^8

Age, Continuous

Sex: Female, Male

Caucasian

African American

Asian

Hispanic

Race/Ethnicity, Customized

Carcinoembryonic Antigen (CEA) Level at Screening

Prior Chemotherapy

KPS 100

KPS 90

KPS 80

The KPS was rated as follows:

100 - Normal, no complaints, no evidence of disease; 90 - Able to carry on normal activity; minor signs or symptoms of disease; 80 - Normal activity with effort; some signs or symptoms of disease

Karnofsky Performance Status (KPS)

Associate Director Regulatory Affairs

Dose limiting adverse events

Nausea

Abdominal pain

Diarrhea

Vomiting

Abdominal pain upper

Constipation

Pyrexia

Chills

Fatigue

Edema peripheral

Back pain

Headache

Anemia

Neutropenia

Rash

Hypokalemia

Insomnia

All Patients

Incidence of Adverse Events and Dose Limiting Adverse Events

Mean Baseline CEA

Mean Change - Chemo visit 1

Mean Change - Chemo visit 2

Mean Change - Follow-up 1

Mean Change - Follow-up 2

Mean Change - Follow-up 3

Mean Change - Follow-up 4

Dose Cohort 1

Dose Cohort 2

Dose Cohort 3

Dose Cohort 4

Number of participants analyzed decreases through the follow-up visits. Thus the "Number of Participants Analyzed" indicated here refer to the number at baseline.

Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy

Patient 101

Patient 102

Patient 103

Patient 201

Patient 202

Patient 203

Patient 301

Patient 302

Patient 303

Patient 304

Patient 401

Patient 402

Patient 403

Patient 801

Patient 802

Patient 803

Patient 804

Patient 805

Patient 806

Patient 807

Patient 808

Patient 809

Patient 810

Patient 811

Patient 812

Patient 813

Patient 814

Patient 815

Patient 816

Patient 817

Patient 818

Patient 819

Escalating doses of NV1020: 3x10\^6 pfu, 1x10\^7 pfu, 3x10\^7 pfu, 1x10\^8 pfu

Stage 1

Stage 2

Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment

Mean Baseline Neutralizing Antibody

Mean Change - Chemotherapy Visit 1

Mean Change - Follow-up Visit 1

Mean Change - Follow-up Visit 2

Mean Change - Follow-up Visit 3

Mean Change - Follow-up Visit 4

Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay

Median time to progression

Median survival time

Time to Disease Progression; Survival Time

NV1020 Pharmacokinetics - Presence of NV1020 in Body Fluids/Skin

Absolute neutrophil count (x10^3/uL)

Basophils (%)

Eosinophils (%)

Hematocrit (%)

Hemoglobin (g/dL)

Lymphocytes (%)

Monocytes (%)

Neutrophils (bands) (%)

Neutrophils (segs) (%)

Platelets (x10^3/uL)

Red blood cells (x10^6/uL)

White blood cells (x10^3/uL)

Clinical Laboratory Safety - Hematology

Alkaline Phosphatase (U/L)

ALT (SGPT) (U/L)

AST (SGOT) (U/L)

Bicarbonate (mmol/L)

BUN (mg/dL)

Calcium (mg/dL)

Chloride (mmol/L)

Creatinine (mg/dL)

Glucose (mg/dL)

Potassium (mmol/L)

Sodium (mmol/L)

Total Bilirubin (mg/dL)

YGT/GGT (U/L)

Clinical Laboratory Safety - Chemistry

C-reactive Protein (mg/dL)

D-dimer (ug/mL)

Fibrinogen (ug/mL)

Prothrombin Time (PT) (sec)

Partial Thromboplastin Time (PTT) (sec)

Clinical Laboratory Safety - Coagulation

Median Baseline INF gamma

Median Change - Visit 1 (post 8 hr)

Median Change - Visit 3 (post 8 hr)

Median Change - Visit 5 (post 8 hr)

Median Change - Visit 7 (post 8 hr)

Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma)

Median Baseline IL-6

Median change - Visit 1 (post 8 hr)

Median change - Visit 3 (post 8 hr)

Median change - Visit 5 (post 8 hr)

Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Treatment of a Cancerous Disease of the Peritoneum With Complete Cytoreductive Surgery and Intraperitoneal Chemohyperthermia	NCT00180960	Colon Tumors Rectum Tumors Appendix Tumors Peritoneum Tumo... Endocrine Tumor...	Oxaliplatin and...	18 Years - 65 Years	Gustave Roussy, Cancer Campus, Grand Paris
Safety & Efficacy of NV1020 in Colorectal Cancer Metastatic to the Liver	NCT00149396	Colorectal Canc... Liver Neoplasms	NV1020	18 Years -	MediGene
Safety & Efficacy of NV1020 in Colorectal Cancer Metastatic to the Liver	NCT00149396	Colorectal Canc... Liver Neoplasms	NV1020	18 Years -	MediGene

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