Phase 3 Trial of Litx™ Plus Chemotherapy vs. Chemotherapy Only Treating Colorectal Cancer Patients With Recurrent Liver Metastases

A Multicenter Multinational Phase 3 Randomized Study to Evaluate the Safety and Efficacy of Treating Colorectal Cancer Patients With Recurrent Liver Metastases Using the Litx™ System Plus Chemotherapy as Compared to Chemotherapy Only

The purpose of the study is to assess the overall survival and progression free survival of patients treated with Litx™ + chemotherapy versus chemotherapy alone in the treatment of Colorectal Cancer with recurrent liver metastases, and to demonstrate the safety of Litx™ therapy.

Litx™ consists of a light-activated drug, talaporfin sodium (LS11, Light Sciences Oncology, Bellevue, Washington), and a light generating device, composed of light-emitting diodes (LEDs), that is energized by a power controller and percutaneously placed in the target tumor tissue inside the body.

Study Overview

• Status: Completed
• Conditions: Neoplasm Metastasis; Colorectal Neoplasms; Liver Metastases; Neoplasm Recurrence, Local
• Intervention / Treatment: Drug: Talaporfin sodium; Procedure: Percutaneous placement of device in liver metastases; Device: Interstitial light emitting diodes; Drug: FOLFOX4 regimen; Drug: FOLFIRI regimen

Detailed Description

Randomized, stratified, two arm study:

• Litx™ and chemotherapy arm (FOLFOX4 or FOLFIRI)
• Chemotherapy only arm (FOLFOX4 or FOLFIRI)

For patients who have progressed on FOLFIRI, they will be treated with Litx™ plus FOLFOX4 versus FOLFOX4 alone; and for patients who have progressed on FOLFOX, they will be treated with Litx™ plus FOLFIRI versus FOLFIRI alone.

Stratification upon enrollment by chemotherapy and tumor sum of the longest diameter (SLD) (SLD < 4 cm or SLD ≥4 cm but ≤7.5 cm).

• Study Type: Interventional
• Enrollment (Actual): 483
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Feldkirch, Austria
    • Landeskrankenhaus Feldkirch
  • Wien, Austria
    • Krankenhaus Hietzing mit Neurologischen Zentrum Rosenhugel
• Bosnia and Herzegovina
  • Mostar, Bosnia and Herzegovina
    • Clinical Hospital Mostar, Internal Clinic, Department of Gastroenterology
  • Sarajevo, Bosnia and Herzegovina
    • Clinical Centre of the University of Sarajevo, Institute of Oncology
• Croatia
  • Karlovac, Croatia
    • General Hospital Karlovac
  • Zagreb, Croatia
    • University Hospital Dubrava
  • Zagreb, Croatia
    • Clinical Centre Zagreb, Clinical Oncology
  • Zagreb, Croatia
    • General Hospital "Sveti Duh"
• Germany
  • Aalen, Germany
    • Ostalb-Klinikum Aalen Darmzentrum Medizinische Klinik I
  • Borna, Germany
    • Helios Kliniken - Innere Medizin und Kardiologie
  • Erfurt, Germany
    • Katholisches Krankenhaus St. Johann Nepomuk
  • Frankfurt, Germany
    • Johann Wolfgang Goethe Universität
  • Ludwigsburg, Germany
    • Kliniken Ludwigsburg Bietigheim
• India
  • Aurangabad, India
    • CIIGMA Institute of Medical Sciences
  • Bhopal, India
    • Jawaharlal Nehru Cancer Hospital and Research Centre
  • Jaipur, India
    • SEAROC Cancer Center, S. K. Soni hospital
  • Mumbai, India
    • Shatabdi Super Specialty Hospital
  • Nagpur, India
    • Cancer Clinic, Shreevardhan complex
  • Pune, India
    • Ruby Hall Clinic
  • Karnataka
    • Bangalore, Karnataka, India
      • Bangalore Institute of Oncology
  • Patna
    • Phulwarisharif, Patna, India
      • Mahavir Cancer Sansthan
• Italy
  • Ancona, Italy
    • Azienda Ospedaliero-Universitaria Riunti
  • Firenze, Italy
    • Azienda Ospedaliera Careggi U.O. Oncologia Medica
  • Padova, Italy
    • Azienda Ospedaliera Universitaria Padovana
  • Rome, Italy
    • Policlinico Tor Vergata - Oncologia Medica
• Latvia
  • Riga, Latvia
    • Riga Eastern Hospital, Latvian Oncology Center
• Poland
  • Kraków, Poland
    • Centrum Onkologii - Instytut im. Marii Skłodowskiej -Curie Oddział w Krakowie
  • Kraków, Poland
    • Szpital Uniwersytecki CMUJ, Klinika Chirurgii Ogólnej i Gastroenterologicznej
  • Lublin, Poland
    • Klinika Chirurgii Onkologicznej
  • Olsztyn, Poland
    • Zakład Opieki Zdrowotnej MSWiA z Warmińsko-Mazurskim Centrum Onkologii
  • Szczecin, Poland
    • Klinika Chirurgii Ogólnej i Onkologicznej
  • Warszawa, Poland
    • Centrum Onkologii - Instytut im. Marii Skłodowskiej -Curie, Klinika Nowotworów Jelita Grubego
  • Łódź, Poland
    • Szpital Wojewódzki im. M. Kopernika, Klinika Chemioterapii Onkologicznej
• Romania
  • Bucharest, Romania
    • Fundeni Clinical Institute
  • Cluj-Napoca, Romania
    • Oncology Institute "Ion Chircuta"
  • Iasi, Romania
    • St. Spiridon University Emergency Hospital
• Russian Federation
  • Barmaul, Russian Federation
    • State Institution "Altay" Territorial Oncological Dispensary
  • Ekaterinburg, Russian Federation
    • State Healthcare Institution "Sverdlovsk' Regional Oncological Dispensary"
  • Moscow, Russian Federation
    • Main Military Clinical Hospital named after Burdenko attached to Ministry of Defense of Russian Federation
  • Moscow, Russian Federation
    • Municipal Cliical Hospital # 33 named after Ostroumov
  • Moscow, Russian Federation
    • Russian Oncological Scientific Center named after Blokhin
  • Nizhny Novgorod, Russian Federation
    • Privolzhsky District Medical Center
  • St. Petersburg, Russian Federation
    • Central Research Institute of Roentgenology and Radiology
  • St. Petersburg, Russian Federation
    • Scientific Research Institution of Oncology
  • St. Petersburg, Russian Federation
    • State Educational Institution of High Professional Education "Military-Medical Academy named after S.M. Kirov attached to Ministry of Defense of Russia"
  • Tambov, Russian Federation
    • Tambov Regional Oncological Dispensary
  • Yaroslavl, Russian Federation
    • State Healthcare Institution of Yaroslavl region, "Regional clinical oncological hospital"
• Serbia
  • Belgrade, Serbia
    • Military Medical Academy
  • Belgrade, Serbia
    • Institute of Oncology and Radiology of Serbia
  • Sremska Kamenica, Serbia
    • Institute of Oncology
• Sweden
  • Stockholm, Sweden
    • Karolinska University Hospital
• Ukraine
  • Cherkassy, Ukraine
    • Municipal Institution "Cherkassy" Regional Oncological Dispensary of Cherkassy
  • Dnepropetrovsk, Ukraine
    • Municipal Multiple-Discipline Clinical Hospital #4
  • Donetsk, Ukraine
    • Donetsk Cancer Centre
  • Kharkov, Ukraine
    • Kharkov Regional Clinical Oncology Dispansery
  • Kyiv, Ukraine
    • The Central Hospital of the Ministry of Defense
  • Zaporozhye, Ukraine
    • Zaporozhye Medical Academy for postgraduate education

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with recurrent metastatic liver lesions from colorectal cancer who progressed on either FOLFOX or FOLFIRI
• Biopsy proven evidence of colorectal cancer
• At least one liver lesion that can be measured in one dimension at >10 mm with spiral CT scan (CT preferred but MRI allowed)
• ECOG Performance Status 0-2
• Life expectancy of at least 16 weeks
• At least 30 days must have elapsed since the completion of any prior antineoplastic therapy and the patient must have recovered from acute side effects before day 0
• Understanding and ability to sign written informed consent
• 18 years of age or more
• Adequate hematologic, liver and renal functions as evidenced by the following: WBC > 2.5 × 10^9/L ; Platelet Count > 100 × 10^9/L ; Hemoglobin > 90 g/L ; Neutrophils >1.5 × 10^9/L ; PT and PTT < 1.5 Control ; SGOT, SGPT < 5 × ULN ; GGT < 5 × ULN ; Alkaline phosphatase < 5 × ULN ; Bilirubin < 3 × ULN ; Creatinine < 1.5 × ULN

Exclusion Criteria:

• Patients who are candidates for complete surgical resection
• Patients who received bevacizumab (Avastin®) or cetuximab (Erbitux®) within 30 days of randomization. Use of bevacizumab or cetuximab is prohibited while participating in this study
• Patients who would require more than a total number of 12 light source applications over three Litx™ experimental treatments (no more than 4 light sources per treatment).
• Patients who have a single measurable tumor greater than 7.5 cm in any organ
• Target lesions irradiated within 3 months of randomization
• Patients with tumor involvement in greater than 50% of parenchyma of the liver
• Evidence of major vessel invasion of any organ
• Patients with any non-colorectal cancers except for adequately treated basal or squamous cell skin cancer, or adequately treated stage I or II cancer from which the patient has been disease-free for ≥ 3 years, or other cancer from which the patient has been disease-free for ≥ 5 years
• Known sensitivity to porphyrin-type drugs or known history of porphyria
• Pregnancy or breast-feeding patients. A negative pregnancy test (urine or serum) from women of childbearing age is required prior to enrollment. A fertile patient must use effective contraception during participation in the study
• Concurrent participation in another clinical trial involving experimental treatment
• Any concurrent disease or condition that in the opinion of the investigator impairs the patient's ability to complete the trial such as psychological, familial, sociological, geographical or medical conditions which in the Principal Investigator's opinion could compromise compliance with the objectives and procedures of this protocol or obscure interpretation of the trial's data.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Litx + Chemotherapy	Drug: Talaporfin sodium; LS11 (Talaporfin Sodium) dose is 1mg/kg administered intravenously slow push (3-5 minutes).; Procedure: Percutaneous placement of device in liver metastases; Light Source placement will be conducted under placement imaging using ultrasound or CT guidance. No more than four Light Sources will be used at a single treatment session. The Light Sources may be used in a single lesion or in multiple lesions.; Device: Interstitial light emitting diodes; 200 J/cm per Light Source at 20 mW/cm light energy; Drug: FOLFOX4 regimen; Standard care chemotherapy regimen consisting of leucovorin, 5-FU and oxaliplatin; Drug: FOLFIRI regimen; Standard care chemotherapy regimen consisting of leucovorin, 5-FU and irinotecan
Active Comparator: Chemotherapy alone	Drug: FOLFOX4 regimen; Standard care chemotherapy regimen consisting of leucovorin, 5-FU and oxaliplatin; Drug: FOLFIRI regimen; Standard care chemotherapy regimen consisting of leucovorin, 5-FU and irinotecan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Time from randomization to death	Up to 184 weeks

Collaborators and Investigators

• Sponsor: Light Sciences Oncology

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: February 23, 2007
• First Submitted That Met QC Criteria: February 23, 2007
• First Posted (Estimate): February 27, 2007

Study Record Updates

• Last Update Posted (Estimate): August 25, 2015
• Last Update Submitted That Met QC Criteria: July 28, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Liver metastases; MCRC; Liver neoplasms; Litx™; LS11; Colorectal cancer with recurrent liver metastases
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Site; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Liver Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Neoplasms; Colorectal Neoplasms; Neoplasm Metastasis; Recurrence; Liver Neoplasms; Neoplasms, Second Primary; Neoplasm Recurrence, Local; Antineoplastic Agents; Photosensitizing Agents; Dermatologic Agents; Talaporfin
• Other Study ID Numbers: LSO-OL006