TF2- Small Cell Lung Cancer Radio Immunotherapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Centre René Gauducheau
Sponsor:
Information provided by (Responsible Party):
Centre René Gauducheau
ClinicalTrials.gov Identifier:
NCT01221675
First received: October 11, 2010
Last updated: November 25, 2013
Last verified: November 2013
  Purpose

Lung cancer is currently the leading cause of cancer death in both men and women in Europe, with an estimated 250000 new cases diagnosed in 2005. The continued poor outcome of patients indicates that the current recommended regimens are falling short. In addition, many of the commonly used chemotherapy agents are associated with severe nonhematologic toxicities that are often cumulative and nonreversible and impair quality of life in this essentially palliative setting. Therefore, agents with novel mechanisms of action and superior safety profiles need to be investigated. More than 50% of lung cancer shows carcinoembryonic antigen (CEA) expression and anti-CEA radioimmunotherapy (RAIT) could be used. The investigators group showed that pretargeted RAIT (PRAIT) using bispecific antibody (bsMAb) can deliver a higher radiation dose to a tumor than a directly radiolabeled anti-CEA antibody, and shows improved anti-tumor efficacy. This clinical trial is designed to assess PRAIT using an entirely new recombinant anti-CEA bsMAb and a 177Lu-labeled peptide for the treatment of CEA-expressing small cell lung cancers (SCLC) or CEA-expressing Non Small Cell Lung Carcinoma (NSCLC)


Condition Intervention Phase
Small Cell Lung Cancer
CEA-expressing Non Small Cell Lung Carcinoma (NSCLC)
Drug: Antibody TF2
Radiation: IMP-288-Lutetium
Radiation: IMP-288-Indium
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospective Multicentric Optimization and Phase I/II Study of Pretargeted Radioimmunotherapy (PRAIT) Using Anti-CEA x Anti-HSG TF2 Bispecific Antibody (bsMAb) and 177Lu-IMP-288 Peptide in Patients With CEA-expressing Small Cell Lung Carcinoma (SCLC) or CEA-expressing Non Small Cell Lung Carcinoma (NSCLC)

Resource links provided by NLM:


Further study details as provided by Centre René Gauducheau:

Primary Outcome Measures:
  • Primary endpoint of study plan I: To determine the optimal TF2 protein dose for pretargeting IMP-288. [ Designated as safety issue: Yes ]
  • Primary endpoint of study plan II • the maximum tolerated dose (MTD) for the TF2-pretargeted 177Lu-IMP-288 under optimal pretargeting conditions. [ Designated as safety issue: Yes ]

Estimated Enrollment: 33
Study Start Date: June 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Antibody TF2
    preciblage with an antibody
    Radiation: IMP-288-Lutetium
    Internal Radiation
    Radiation: IMP-288-Indium
    Imaging
Detailed Description:

The purpose of this open-label prospective optimization and phase I/II clinical trial is to examine the safety, optimal dose, targeting, dosimetry and efficacy of PRAIT using the humanized anti-CEA x anti-HSG bsMAb TF2 and the 177Lu-IMP-288 peptide pretargeted in patients with CEA-positive SCLC or CEA-expressing Non Small Cell Lung Carcinoma (NSCLC)

This study has 2 parts: Study plan I (Optimization study) and Study plan II (Escalating activity phase I/II study).

The Study plan I is designed to optimize the pretargeting procedure using blood pharmacokinetics (Pk) and dosimetry in 9 patients receiving escalating doses of TF2 followed 2 to 4 days later by 1.1 GBq/m2 of 177Lu-IMP-288.

The study plan II is designed to determined MTD of 177Lu-IMP-288 using dosimetry and toxicity data in a phase I/II study performed in patients receiving optimal dose of TF2 bsMAb (determined in study plan I) followed 2 to 4 days by escalating activity of 177Lu-IMP-288.

A pre-therapy imaging study (using TF2 followed 2 to 4 days later by 185 MBq of 111In-IMP-288) is performed in the two study plans to qualify a patient for treatment with the subsequent therapy dose.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

• Patients with histologic diagnosis of SCLC who are in partial response or who have failed at least two lines of standard radiation and/or chemotherapy. Outside formal contra-indication, patients must have received at least one prior platinum-based chemotherapy.

or

  • Patients with histologic diagnosis of NSCLC (without activating mutation of EGFR gene) who have failed at least one line of chemotherapy (platinum in combination with a third generation drug or combination of 2 third generation drug +/-bevacizumab in case of predominance of non-squamous tumor)
  • Age ≥ 18 years
  • At least 4-weeks after the previous treatment and have recovered from previous radio- or chemotherapy
  • Women of child-bearing potential must have a negative pregnancy test.
  • Karnofsky performance status ≥ 60 or ECOG performance status 0-2Karnofsky
  • Minimum life expectancy of 3 months
  • Positive CEA on immunohistology or plasma CEA ≥ 10 ng/mL
  • At least one measurable lesion by CT
  • At least one abnormal focus by FDG-PET
  • Imaging studies must be performed within 1-4 weeks before PRAIT study to document extent of disease
  • Signed informed consent form.

Exclusion Criteria:

  • Pregnant or lactating woman. Women of child-bearing potential will be asked to practice adequate means of birth control for a minimum of 12 months after treatment.
  • Male patient refusing effective contraception for a minimum of 12 months after treatment.
  • Brain metastases but patients with brain metastases controlled after treatment by Surgery or radiotherapy since more than 4 weeks are eligibles for the study. An treatment by associated corticotherapy is authorized for these patients.
  • Known HIV or hepatitis
  • Any serious active disease or comorbid medical condition (according to the investigator's decision and information provided in the IDB)
  • Severe disorders of hemostasis or anticoagulant treatment cure
  • Extensive irradiation to more than 25% of their red marrow
  • Bone marrow involvement to more than 25%
  • External radiation to specific organs or areas at the maximum tolerated level
  • EGFR gene mutation in tumor (only for NSCLC)
  • Febrile aplasia during a previous chemotherapy
  • Neutrophils < 1.5 G/l
  • Platelets < 100 G/l
  • Uncontrolled diabetes
  • Poor renal function (creatinine level > 2.5 maximum normal level)
  • Poor hepatic function (total bilirubin level > 30 mmol/l, transaminases > 2.5 maximum normal level)
  • Treatment with any investigational drug within 30 days before planned PRAIT and during the study
  • Any history of cancer during the last 5 years, with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma,
  • Presence of anti-antibody reactivity
  • Known hypersensitivity to murine antibodies or proteins
  • Adult patient unable to give informed consent because of intellectual impairment.
  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: NCT01221675

Locations
France
CHU d'Angers Recruiting
Angers, France, 49100
Contact: Oliver couturier, MD       "Couturier Olivier Francois" <ocouturier70@me.com>   
Contact: Evelyne Scotet-Cérato, PhD       evelyne.cerato@chu-nantes.fr   
CHU Recruiting
Brest, France, 29000
Contact: Pierre Yves Salaün, MD       pierre-yves.salaun@chu-brest.fr   
Hôpital La tronche Recruiting
Grenoble, France, 38000
Contact: Jean Philippe Vuillez, MD       JPVuillez@chu-grenoble.fr   
Hotel Dieu Recruiting
Nantes, France, 44093
Contact: Françoise Bodere, MD       françoise.bodere@chu-nantes.fr   
Centre Eugène Marquis Not yet recruiting
Rennes, France, 35000
Contact: Etienne Garin, MD       e.garin@rennes.fnclcc.fr   
Centre René Gauducheau Recruiting
Saint Herblain, France, 44805
Contact: Françoise Bodere, MD    +33240679900      
CHU Rangueil Not yet recruiting
Toulouse, France, 31000
Contact: Fréderic Courbon, MD       Courbon.Frederic@claudiusregaud.fr   
Sponsors and Collaborators
Centre René Gauducheau
  More Information

No publications provided

Responsible Party: Centre René Gauducheau
ClinicalTrials.gov Identifier: NCT01221675     History of Changes
Other Study ID Numbers: BRD 08/9-O
Study First Received: October 11, 2010
Last Updated: November 25, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre René Gauducheau:
Small Cell Lung Cancer or CEA-expressing Non Small Cell Lung Carcinoma (NSCLC)
Radio Immunotherapy
Lutetium
patient ≥ 18 years of age with CEA-positive SCLC in partial response
or who failed at least two lines of standard radiation and/or chemotherapy
or Patients with histologic diagnosis of NSCLC

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Small Cell Lung Carcinoma
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Antibodies
Immunoglobulins
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014