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

NCT00149396 | Completed Phase 1 Results DMC

• 1 other identifier: CT1030
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Colorectal Cancer; Liver Neoplasms

Keywords

Colorectal cancer metastases to liver; Colorectal Cancer; Colorectal Carcinoma; Colorectal Tumors; Colorectal Neoplasms; Rectum Cancer; Rectum tumors; Rectum carcinoma; Colon cancer; Colon tumors; Colon carcinoma; Rectum Neoplasms; Colon Neoplasms; Liver Neoplasms; Hepatic Neoplasms; Liver Tumors; Liver cancer; Hepatic Cancer; Hepatic tumors; metastatic to the liver

Outcome Measures

Primary Outcomes (5)

• Incidence of Adverse Events and Dose Limiting Adverse Events

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

  From start of treatment through 12 months after completion of treatment

• NV1020 Pharmacokinetics - Presence of NV1020 in Body Fluids/Skin

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

  Daily for 2 weeks after the first and last NV1020 infusions

• Clinical Laboratory Safety - Hematology

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

  Screening; after each NV1020 infusion; +7h, +24h, and +72h after NV1020 infusion; each chemotherapy visit; +3d, +7d, +14d after each chemo visit; 1 week after end of treatment

• Clinical Laboratory Safety - Chemistry

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

  Screening; after each NV1020 infusion; +7h, +24h, and +72h after NV1020 infusion; each chemotherapy visit; +3d, +7d, +14d after each chemo visit; 1 week after end of treatment

• Clinical Laboratory Safety - Coagulation

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

  Screening; after each NV1020 infusion; +7h, +24h, and +72h after NV1020 infusion; each chemotherapy visit; +3d, +7d, +14d after each chemo visit; 1 week after end of treatment

Secondary Outcomes (7)

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

  Screening (baseline), Chemo visit 1, Chemo visit 2, Follow-up Visit 1 (1 week after end of treatment), Follow-up Visit 2 (+6M), Follow-up Visit 3 (+9M), Follow-up Visit 4 (+12M)

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

  Screening (baseline), Chemo visit 1, Follow-up visits 1 (1 week post end of treatment), 2 (+6M), 3 (+9M), 4 (+12M)

• Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay

  Screening, Chemo Visit 1, Follow-up Visits 1 (1 week post end of treatment), 2 (+6M), 3 (+9M), 4 (+12M)

• Time to Disease Progression; Survival Time

  Progression: Chemo visit 1, FU1 (1 week post treatment), FU2 (+6M), FU3 (+9M), FU4 (+12M); Survival: death of patient

• Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma)

  Baseline, after each NV1020 infusion (Visit 1, Visit 3, Visit 5, Visit 7)

Study Arms (1)

Safety and antitumor effects of NV1020

EXPERIMENTAL

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.

Drug: NV1020

Interventions

NV1020 DRUG

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

Safety and antitumor effects of NV1020

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and willingness to sign a written informed consent (includes willingness to avoid physical intimacy during and for 2 weeks post NV1020 treatment)
• years or more of age
• Colorectal adenocarcinoma histologically confirmed within one year prior to enrollment in the study
• Liver dominant metastases (CT-measurable lesions with less than 50% total liver involvement), histologically confirmed
• Failed conventional chemotherapy for metastatic disease (e.g. tumors no longer responding to 5-FU/leucovorin in combination with irinotecan or oxaliplatin with or without one monoclonal antibody)
• Candidate for additional chemotherapy (and/or experimental anti-cancer therapy, if this is the only remaining treatment option)
• Karnofsky Performance Status 70% or greater
• Life expectancy greater than or equal to 4 months, based on the investigator's opinion
• Seropositive for herpes simplex virus-1 (HSV-1)
• Fecund females: negative for pregnancy test (urine or serum)
• Effective double-barrier contraception for a minimum of 2 months following final infusion of NV1020

You may not qualify if:

• Dominant extrahepatic disease, including cerebral metastases, significant malignant ascites or other extrahepatic metastases that are symptomatic, in critical locations or otherwise likely to confound NV1020 evaluations, in the opinion of the investigator
• Seronegative for HSV-1
• Significant active/unstable non-malignant disease or laboratory test (hematology and chemistry) results that meet any of the following:
• White blood cell count (WBC) less than or equal to 3 x 10e3/mm3
• Absolute neutrophil count (ANC) less than or equal to 1.5 x 10e3/mm3
• Platelets less than or equal to 100,000/mm3
• Hemoglobin (Hgb) less than or equal to 9.0 g/dL
• Prothrombin time/partial thromboplastin time (PT/PTT) \> upper limit of normal (ULN)
• Serum creatinine \> 2.0 mg/dL
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 times ULN or total bilirubin \> 1.5 times ULN
• Alkaline phosphatase \> 2.5 times ULN
• Chemotherapy \< 4 weeks prior to the first NV1020 infusion (mitomycin or nitrosurea \< 6 weeks)
• Immunotherapy \< 6 weeks prior to the first NV1020 infusion
• Radiotherapy (external or internal) to the liver
• Major surgery (excluding pump placement and cholecystectomy) ≤ 2 weeks prior to the first NV1020 infusion but the subject must be clinically stable. Pump placement and cholecystectomy ≤ 1 week prior to the first NV1020 infusion but the subject must be clinically stable

Sponsors & Collaborators

• MediGene: lead

Study Sites (5)

University of California, San Diego

San Diego, California, 92093, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Pittsburgh Cancer Center

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Vanderbilt

Nashville, Tennessee, 37232, United States

Location

Mary Crowley Medical Research Center

Dallas, Texas, 75201, United States

Location

Related Publications (1)

• Sze DY, Iagaru AH, Gambhir SS, De Haan HA, Reid TR. Response to intra-arterial oncolytic virotherapy with the herpes virus NV1020 evaluated by [18F]fluorodeoxyglucose positron emission tomography and computed tomography. Hum Gene Ther. 2012 Jan;23(1):91-7. doi: 10.1089/hum.2011.141. Epub 2011 Oct 14.

  PMID: 21895536 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Liver Neoplasms; Rectal Neoplasms; Colonic Neoplasms; Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Associate Director Regulatory Affairs
• Organization: Medigene

p.larson@medigeneusa.com

858-586-2252

Study Officials

• Hoda Tawfik, PhD

  MediGene

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2005
• First Posted: September 8, 2005
• Study Start: July 1, 2004
• Primary Completion: October 1, 2008
• Study Completion: December 1, 2008
• Last Updated: April 24, 2018
• Results First Posted: April 24, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)