A Pilot Study of Radiation-Immune Cell Combination Therapy in Cervical Cancer

This study has been terminated.
(No further enrollment after two patients)
Sponsor:
Information provided by (Responsible Party):
Sang-Young Ryu, Korea Cancer Center Hospital
ClinicalTrials.gov Identifier:
NCT01194609
First received: September 2, 2010
Last updated: May 7, 2014
Last verified: May 2014
  Purpose

Among the immune cell therapy, autologous adoptive immune cell therapy is a method to transfer the immune cells derived from peripheral white blood cells and expanded and stimulated with various cytokines and tumor specific antigens in cancer patients. Recently, the low-dose radiation is known to increase the immune response in many human cancer patients. In a clinical trial, 70% response rate with combination of low-dose radiation and adoptive immune cell therapy was reported in recurrent melanoma patients. This study is to investigate the feasibility of combination of low-dose radiation and autologous immune cell therapy in recurrent cervical cancer which is resistant to conventional palliative treatment.


Condition Intervention Phase
Uterine Cervical Neoplasms
Biological: Immune cell
Radiation: Low dose radiation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Radiation-Immune Cell Combination Therapy in Recurrent or Persistent Cervical Cancer

Resource links provided by NLM:


Further study details as provided by Korea Cancer Center Hospital:

Primary Outcome Measures:
  • Response rate [ Time Frame: 12months ] [ Designated as safety issue: Yes ]
    Response rate according to RECIST criteria for 12 months


Secondary Outcome Measures:
  • Toxicity [ Time Frame: 12months ] [ Designated as safety issue: Yes ]
    Toxcity according to CTCSEver4.0


Enrollment: 2
Study Start Date: September 2010
Study Completion Date: April 2012
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Low dose radiation, Immune cell therapy
Combination treatment of low-dose radiation 20cGy every 3 weeks three times and autologous immune cell therapy 2 consecutive weeks 3 times every 3 weeks
Biological: Immune cell
InnoLak two consecutive weeks every 3 weeks for 3 times
Other Name: InnoLAK
Radiation: Low dose radiation
20cGy whole body radiation every three weeks for three times
Other Name: Whole body radiation

Detailed Description:

Immune cell therapy is considered one of the most promising anti-cancer strategy in many human cancers. Compared to the destructive methods such as surgery, radiation, and chemotherapy, anti-cancer immune therapy is safer and less toxic method in the treatment of human cancer patients.

Among the immune cell therapy, autologous adoptive immune cell therapy is a method to transfer the immune cells derived from peripheral white blood cells and expanded and stimulated with various cytokines and tumor specific antigens in cancer patients. Recent development of the technique to expand immune cells ex vivo make autologous adoptive immune cell therapy much more feasible and popular. However, immune cell therapy showed response of below 10% currently in several clinical trials. The reason of poor response is that the adopted immune cells have to overcome the highly immune compromised environment in advanced or recurrent cancer patients.

The low-dose radiation, defined as the radiation below the therapeutic dose range, is known to increase the immune response in many human cancer patients. Despite the exact mechanism is not well known, the 'danger signal' and the decrease of T-regulatory cells by low-dose radiation are the possible mechanism of enhanced immunity by low-dose radiation. So, the combination of low-dose radiation and immune cell therapy can be a attractive strategy to recurrent or advanced cancer patients who are resistant to conventional treatment.

A challenging clinical trial performed in recurrent melanoma cancers, Dr. Rosenverg reported around 70% response rate with combination of low-dose radiation and adoptive immune cell therapy. However, the feasibility of combination of low-dose radiation and immune cell therapy is still unknown in many human cancers.

This study is to investigate the feasibility of combination of low-dose radiation and autologous immune cell therapy in recurrent cervical cancer which is resistant to conventional palliative treatment. The cervical cancer, highly responsive to radiation, becomes resistant to radiation in case of recurrent disease. We hypothetize that if the low-dose radiation can reverse the immune compromised environment, adoptive immune cells derived from the autologous peripheral blood immune cells will be highly effective in recurrent cervical cancers.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have signed an approved informed consent and authorization permitting release of personal health information.
  2. Age 18-75 years
  3. Pathologically proven recurrent or persistent cervical cancer patients resistant to conventional palliative chemotherapy or radiation therapy

    1. Persistent tumor more than 1cm after initial chemoradiation or radiation therapy
    2. Persistent tumor more than 1cm after chemoradiation, radiation or chemotherapy in recurrent cervical cancer
    3. Metastatic cervical cancer to lung resistant to conventional chemotherapy
  4. ECOG performance status 0, 1, 2.
  5. Expected survival more than 3 months
  6. Patients must have adequate:

    Hematologic function: ANC ≥ 1,500/mcl, Hemoglobin >10g/dL, platelets ≥ 100,000/mcl Renal function: creatinine ≤ 1.5 x ULN Hepatic function: AST, ALT ≤ 1.5 x ULN,

  7. More than 3 weeks from the last day of previous chemotherapy or radiation

Exclusion Criteria:

  1. Patients with immune disease or auto-immune disease (ex. rheumatoid arthritis, SLE, immune vasculitis, IDDM)
  2. Immune deficiency disease
  3. Cancers other than cervical cancer within 5 years
  4. Acute myocardial infarction, uncontrolled hypertension
  5. Severe allergic disease
  6. Severe psychotic disease
  7. Those who can be a candidate for curative surgery
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01194609

Locations
Korea, Republic of
Sang-Young Ryu
Seoul, Nowon‐Gu, Korea, Republic of, 139-706
Sponsors and Collaborators
Korea Cancer Center Hospital
Investigators
Principal Investigator: Sang-Young Ryu, MD Korea Institute of Radiological & Medical Sciences
  More Information

No publications provided

Responsible Party: Sang-Young Ryu, A staff at department of obstetrics and gynecology, Korea Cancer Center Hospital
ClinicalTrials.gov Identifier: NCT01194609     History of Changes
Other Study ID Numbers: RadImmune Cx-1001
Study First Received: September 2, 2010
Last Updated: May 7, 2014
Health Authority: Korea: Food and Drug Administration

Keywords provided by Korea Cancer Center Hospital:
Low dose radiation
Adoptive immune cell therapy
Cervical cancer
Pilot study

Additional relevant MeSH terms:
Neoplasms
Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female

ClinicalTrials.gov processed this record on July 31, 2014