Neoplasms

Digestive System Diseases

All Conditions

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Laparoscopy-assisted pelvic autonomic nerve preservation total mesorectum excision for male mid-low rectal cancer patients

Open pelvic autonomic nerve preservation total mesorectum excision for male mid-low rectal cancer patients

L-PANP-TME

O-PANP-TME

Hongbo Wei, M.D. Ph.D.

Hongbo Wei, M.D., Ph.D.

TME (Total mesorectum excision) is the golden standard of radical resection for mid-low rectal cancer. However, the damage of pelvic autonomic nerve following with TME principle will lead to high incidence of urinary and sexual function disorder. Open PANP (pelvic autonomic nerve preservation) TME surgery played a role in decreasing incidence of urinary and sexual function disorder. However, 32%-44% patients still suffered from urinary and sexual function disorder when underwent Open PANP TME surgery (O-PANP-TME).

Laparoscopy-assisted TME surgery (L-TME) is applied wildly nowadays. In the early stage of work, we performed laparoscopy-assisted PANP TME surgery (L-PANP-TME) to discuss the protection of urinary and sexual function of male mid-low rectal cancer patients. The results showed that L-PANP-TME significantly decreased incidence of urinary and sexual function disorder. In order to further confirm our early work, we design a randomized controlled clinical trial to compare differences in urinary and sexual function protection and long-term outcomes between L-PANP-TME and O-PANP-TME.

Laparoscopic Versus Open PANP-TME for Male Mid-low Rectal Cancer Patients

Comparisons of Urinary and Sexual Function Protection and Long-term Outcomes Between Laparoscopy-assisted and Open Pelvic Autonomic Nerve Preservation Total Mesorectum Excision for Male Mid-low Rectal Cancer Patients: a Randomized Controlled Clinical Trial

Urodynamic study and IPSS (International prostate symptom score) are used to assess urinary function

IIEF-5 (International questionnaire of erectile function-5) and Ejaculation function classification are used to assess sexual function

Third Affiliated Hospital, Sun Yat-Sen University

Chief of surgery

Hongbo Wei, M.D,Ph.D.

TME (Total mesorectum excision) is the golden standard of radical resection for mid-low rectal cancer. However, the damage of pelvic autonomic nerve following with TME principle will lead to high incidence of urinary and sexual function disorder. Open PANP (pelvic autonomic nerve preservation) TME surgery played a role in decreasing incidence of urinary and sexual function disorder. However, 32%-44% patients still suffered from urinary and sexual function disorder when underwent Open PANP TME surgery (O-PANP-TME).

Laparoscopy-assisted TME surgery (L-TME) is applied wildly nowadays. In the early stage of work, we performed laparoscopy-assisted PANP TME surgery (L-PANP-TME) to discuss the protection of urinary and sexual function of male mid-low rectal cancer patients. The results showed that L-PANP-TME significantly decreased incidence of urinary and sexual function disorder. In order to further confirm our early work, we design a multiple-center randomized controlled clinical trial to compare differences in urinary and sexual function protection and long-term outcomes between L-PANP-TME and O-PANP-TME.

Multicenter Study on Laparoscopic Versus Open PANP-TME for Male Mid-low Rectal Cancer Patients

Multicenter Study on Outcomes and Protection of Urinary and Sexual Function of Laparoscopic Versus Open PANP-TME for Male Mid-low Rectal Cancer Patients

First Affiliated Hospital, Sun Yat-Sen University

Sixth Affiliated Hospital, Sun Yat-sen University

Nanfang Hospital, Southern Medical University

Southern Medical University, China

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Capecitabine

Leucovorin

Fluorouracil

Levoleucovorin

Oxaliplatin

Folic Acid

Tetrahydrofolates

Formyltetrahydrofolates

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antidotes

Protective Agents

Vitamin B Complex

Trace Elements

Folinic Acid

Folate

Vitamin B9

* Radiotherapy will consist of five fractions, delivered once daily, to a total dose of 25Gy at 5 Gy per fraction.
* An optional concomitant boost may be delivered to the primary tumor of 1-2 Gy per day (30-35 Gy to tumor total). If a boost is given then the maximum allowed dose to small bowel is 25 Gy.
* Chemotherapy should begin two weeks (9-12 working days) after completion of radiotherapy.
* Oxaliplatin will be given intravenous (IV) over 2 hours on Day 1 every 14 days for a maximum of 8 cycles.
* Leucovorin will be given IV over 2 hours on Day 1 every 14 days for a maximum of 8 cycles.
* 5-FU bolus will given IV push on Day 1 every 14 days for a maximum of 8 cycles.
* 5-FU infusion will be given continuous IV on Day 1 over 46 hours every 14 days for a maximum of 8 cycles
* Alternatively, capecitabine/oxaliplatin (CAPE PO 1000 mg/m2 BID days 1-14 Q21 days, oxaliplatin IV 130 mg/m2 IV Q21 days on day 1) x 5 cycles over 15 weeks may be administered instead of FOLFOX

Radiation

Hyun Kim, M.D.

The purpose of this research study is to look at how tumors responds to a short course of radiation (5 days) followed by 8 cycles of chemotherapy.

Non-Operative Radiation Management of Adenocarcinoma of the Lower Rectum

Non-Operative Radiation Management of Adenocarcinoma of the Lower Rectum (NORMAL-R)

* Criteria for complete clinical response:

  * No residual gross tumor at procto/sigmoidoscopy, or only erythematous scar or ulcer
  * No radiographic evidence of tumor on DRE
  * Substantial downsizing on MRI
  * No suspicious mesorectal lymph nodes on MRI
  * Negative biopsy from scar, ulcer, or former tumor site (if necessary according to surgeon's judgment)
* Criteria for no significant clinical response:

  * Residual disease by DRE, endoscopy or MR.
  * Increase in primary tumor size upon clinical exam or imaging
  * Any new lesions

-The FACT-C questionnaire is broken down into physical well-being, social/family well-being, emotional well-being, and functional well-being. The answers range from 0 (not at all) to 4 (very much).

-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.

-The FACT-C questionnaire has 2 statements about anorectal function and the participant answers 0 (not at all) to 4 (very much)

Washington University School of Medicine

Arm 1: Radiation/Oxaliplatin/Leucovorin/5-FU

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

1 participant was not evaluable for this outcome measure as they were removed for an adverse event

Complete Response Rate

I have a lack of energy

I have nausea

Because of my physical condition, I have trouble meeting the needs of my family

I have pain

I am bothered by side effects of treatment

I feel ill

I am forced to spend time in bed

I feel close to my friends

I get emotional support from my family

I get support from my friends

My family has accepted my illness

I am satisfied with family communication about my illness

I feel close to my partner (or the person who is my main support)

I am satisfied with my sex life

I feel sad

I am satisfied with how I am coping with my illness

I am losing hope in the fight against my illness

I feel nervous

I worry about dying

I worry that my condition will get worse

I am able to work (include work at home)

My work (include work at home) is fulfilling

I am able to enjoy life

I have accepted my illness

I am sleeping well

I am enjoying the things I usually do for fun

I am content with the quality of my life right now

I have swelling or cramps in my stomach area

I am losing weight

I have control of my bowels

I can digest my food well

I have diarrhea (diarrhoea)

I have a good appetite

I like the appearance of my body

I am embarrassed by my ostomy appliance

Caring for my ostomy appliance is difficult

-Participant is asked about specific well-being in the past 7 days

0=Not at All

1=A Little Bit

2=Somewhat

3=Quite a Bit

4=Very Much

-Participant did not answer question about well-being

Prefer Not to Answer/No Answer/No

Prospective Patient Reported Outcomes as Measured by FACT-C Questionnaire

One participant was not evaluable for this outcome measure because they did not complete chemoradiation.

One participant was not evaluable for this outcome measure because they did not complete chemoradiation. One participant was not evaluable for this outcome measure because they expired prior to this timepoint.

Anemia

Febrile neutropenia

Cardiac arrest

Myocardial infarction

Ventricular fibrillation

Abdominal pain

Diarrhea

Pancreatitis

Fever

Cholectystitis

Lung infection

Fall

Activated partial thromboplastin time prolonged

Aspartate aminotransferase increased

Cardiac troponin I increased

Cardiac troponin T increased

Lymphocyte count decreased

Neutrophil count decreased

White blood cell decreased

Dehydration

Hyperglycemia

Hypokalemia

Hyponatremia

Generalized muscle weakness

Peripheral sensory neuropathy

Syncope

Respiratory failure

Aspiration

Dyspnea

Hypoxia

Palmar-plantar erythrodysesthesia syndrome

Cellulitis

Hypertension

Hypotension

Thromboembolic event

Number of Any Grade 3 or Higher Toxicities

Cholecystitis

White blood cell count decreased

Number of Post Chemotherapy Grade 3 or Higher Toxicities

Quality of Anorectal Function as Measured by the FACT-C Questionnaire

Overall Study

Symptoms and General Pathology

Neoplasm Metastasis

Colonic Neoplasms

Liver Neoplasms

Colonic Diseases

Liver Diseases

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Laparoscopic Versus Open PANP-TME for Male Mid-low Rectal Cancer Patients	NCT02164136	Rectum Neoplasm...	L-PANP-TME O-PANP-TME	20 Years - 60 Years	Third Affiliated Hospital, Sun Yat-Sen University
Multicenter Study on Laparoscopic Versus Open PANP-TME for Male Mid-low Rectal Cancer Patients	NCT02165800	Rectum Neoplasm...	L-PANP-TME O-PANP-TME	20 Years - 60 Years	Third Affiliated Hospital, Sun Yat-Sen University
Non-Operative Radiation Management of Adenocarcinoma of the Lower Rectum	NCT02641691	Cancer of Rectu... Cancer of the R... Neoplasm, Rectu... Rectal Cancer Rectum Cancer Rectum Neoplasm... Adenocarcinoma ...	Radiation Oxaliplatin Leucovorin Fluorouracil	18 Years -	Washington University School of Medicine
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
Laparoscopic Versus Open PANP-TME for Male Mid-low Rectal Cancer Patients	NCT02164136	Rectum Neoplasm...	L-PANP-TME O-PANP-TME	20 Years - 60 Years	Third Affiliated Hospital, Sun Yat-Sen University

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