TF2- Small Cell Lung Cancer Radio Immunotherapy

August 30, 2016 updated by: Centre René Gauducheau

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)

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)

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Angers, France, 49100
        • CHU d'Angers
      • Brest, France, 29000
        • CHU
      • Clermont Ferrand, France
        • Centre Jean Perrin
      • Grenoble, France, 38000
        • Hôpital La Tronche
      • Nantes, France, 44093
        • Hôtel Dieu
      • Saint Herblain, France, 44805
        • Centre René Gauducheau

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Primary endpoint of study plan I: To determine the optimal TF2 protein dose for pretargeting IMP-288.
Primary endpoint of study plan II • the maximum tolerated dose (MTD) for the TF2-pretargeted 177Lu-IMP-288 under optimal pretargeting conditions.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Centre René Gauducheau

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 11, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 14, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 15, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 31, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 30, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BRD 08/9-O

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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