Radio-Immuno-Modulation in Lung Cancer

NCT02579005 | Suspended Phase 1 DMC

• 1 other identifier: 2012-634
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This project will assess the feasibility of treating advanced cancer using the immune system, without any anti-cancer drug. In this pilot study, the investigators propose combining low-dose radiotherapy, in lung cancer patients, with allogeneic immune cells obtained from a donor. The patients will receive radiotherapy directed to one of the patient's tumors, as well as an immunomodulatory drug called cyclophosphamide. Thereafter, they will receive the infusion of donor immune cells.

Conditions

Lung Cancer

Keywords

Radiation; Immune response; Anti-tumor; Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-related adverse events

  Evaluation by follow-up clinic visits, including medical questionnaire, physical exam \& blood tests: complete blood count, electrolytes, renal \& liver function tests. AE will be graded using National Cancer Institute's Common Toxicity Criteria version 3 (7). Evaluations will take place twice a week for the first 2 weeks, weekly for 2 weeks, every 2 weeks for 2 months \& every month for 3 months. It is anticipated that a maximum of 1 of 6 patients will have grade 3 side effects, including nausea, diarrhea, dyspnea, cough, fever, rash.

  Up to 6 months

Secondary Outcomes (4)

• Immune responses - T cell infiltration

  Up to 1 month

• Immune responses - Tumor cell phenotype

  Up to 1 month

• Immune responses - tumor infiltrating T cell phenotype

  Up to 1 month

• Immune responses - origin of tumor infiltrating T cells

  Up to 1 month

Study Arms (2)

Patients with a living donor

EXPERIMENTAL

Radiation + PBMC

Biological: Patients with a living donor

Patients with a UCB donor

EXPERIMENTAL

Radiation + UCB

Biological: Patients with a UCB donor

Interventions

Patients with a living donor BIOLOGICAL

The day of allogeneic cell infusion will be referred to as Day 0 and the n-th day before that, as Day -n. The dose of external radiation will be 15 Gy divided in 3 fractions, from Day -3. Cyclophosphamide, 250 mg/m2 will be given on Day -2. Donors will receive 5 daily doses of GCSF, 10 µg/kg, by subcutaneous injection from Day -4. PBMC will be collected through apheresis on Day 0. A dose of 5 x 10exp7 CD3 cells/kg will be administered. The infused volume will be adjusted to contain this T cell dose.

Patients with a living donor

Patients with a UCB donor BIOLOGICAL

The day of allogeneic cell infusion will be referred to as Day 0 and the n-th day before that, as Day -n. The UCB unit should have at least 4 of 6 HLA compatibility and at least 3 x 10exp6 TNC per kg patient weight. The dose of external radiation will be 15 Gy, divided in 3 fractions, starting on Day -3. Cyclophosphamide, 250 mg/m2 intravenously, will be given on Day -2.

Patients with a UCB donor

Eligibility Criteria

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

You may qualify if:

• Advanced lung cancer documented by a histo-pathological analysis;
• Patients who received at least one line of anti neoplastic therapy;
• Presence of at least one tumor mass \>1 cm and not previously irradiated;
• Metastases situated in one of the following sites: lung, skeleton, lymph nodes or soft tissue;
• Presence of at least one not previously irradiated metastasis;
• Life expectancy greater than 3 months;
• ECOG performance status ≤ 2.

You may not qualify if:

• Second active cancer necessitating treatment;
• History of autoimmune disease;
• Patients dependent on immunosuppressive medications, including corticosteroids;
• Decreased diffusion capacity below 40%, if radiation planned to a lung metastasis;
• Patients needing urgent radiotherapy.

Sponsors & Collaborators

• Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal: lead
• Maisonneuve-Rosemont Hospital: collaborator

Study Sites (1)

Hopital Sacre-Coeur

Montreal, Quebec, H4J 1C5, Canada

Location

Related Publications (7)

• Hodge JW, Guha C, Neefjes J, Gulley JL. Synergizing radiation therapy and immunotherapy for curing incurable cancers. Opportunities and challenges. Oncology (Williston Park). 2008 Aug;22(9):1064-70; discussion 1075, 1080-1, 1084.

  PMID: 18777956 BACKGROUND

• Brody JD, Ai WZ, Czerwinski DK, Torchia JA, Levy M, Advani RH, Kim YH, Hoppe RT, Knox SJ, Shin LK, Wapnir I, Tibshirani RJ, Levy R. In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a phase I/II study. J Clin Oncol. 2010 Oct 1;28(28):4324-32. doi: 10.1200/JCO.2010.28.9793. Epub 2010 Aug 9.

  PMID: 20697067 BACKGROUND

• Chi KH, Liu SJ, Li CP, Kuo HP, Wang YS, Chao Y, Hsieh SL. Combination of conformal radiotherapy and intratumoral injection of adoptive dendritic cell immunotherapy in refractory hepatoma. J Immunother. 2005 Mar-Apr;28(2):129-35. doi: 10.1097/01.cji.0000154248.74383.5e.

  PMID: 15725956 BACKGROUND

• Gulley JL, Arlen PM, Bastian A, Morin S, Marte J, Beetham P, Tsang KY, Yokokawa J, Hodge JW, Menard C, Camphausen K, Coleman CN, Sullivan F, Steinberg SM, Schlom J, Dahut W. Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer. Clin Cancer Res. 2005 May 1;11(9):3353-62. doi: 10.1158/1078-0432.CCR-04-2062.

  PMID: 15867235 BACKGROUND

• Diaconescu R, Storb R. Allogeneic hematopoietic cell transplantation: from experimental biology to clinical care. J Cancer Res Clin Oncol. 2005 Jan;131(1):1-13. doi: 10.1007/s00432-004-0611-6. Epub 2004 Sep 28.

  PMID: 15565456 BACKGROUND

• Baron F, Maris MB, Sandmaier BM, Storer BE, Sorror M, Diaconescu R, Woolfrey AE, Chauncey TR, Flowers ME, Mielcarek M, Maloney DG, Storb R. Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. J Clin Oncol. 2005 Mar 20;23(9):1993-2003. doi: 10.1200/JCO.2005.08.136.

  PMID: 15774790 BACKGROUND

• 7. Cancer Therapy Evaluation Program. Common Terminology Criteria for Adverse Events v3.0 (CTCAE). Bethesda, MD. National Cancer Insitute, 2006. Available at: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf.

  BACKGROUND

MeSH Terms

Conditions

Lung Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Razvan B Diaconescu, MD

  CIUSSS du Nord-de-l'Île-de-Montréal - Hôpital du Sacré-Cœur de Montréal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Hematologist-Oncologist

Study Record Dates

• First Submitted: October 7, 2015
• First Posted: October 19, 2015
• Study Start: April 20, 2018
• Primary Completion: October 1, 2024
• Study Completion: April 1, 2025
• Last Updated: February 29, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)