TF2- Small Cell Lung Cancer Radio Immunotherapy
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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).
| Condition | Intervention | Phase |
|---|---|---|
|
Small Cell Lung Cancer |
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) |
- 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 Primary Completion Date: | June 2015 (Final data collection date for primary outcome measure) |
-
Drug: Antibody TF2
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.
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 |
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
- 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 ≥ 70 or ECOG performance status 0-1
- 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.
- 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
- Known HIV or hepatitis
- Any serious active disease or co-morbid 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 toletared level
- Febrile aplasia during a previous chemotherapy
- Neutrophils < 1.5 G/l
- Platelets < 100 G/l
- Uncontrolled diabetes
- Poor renal function (creatinin 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.
Exclusion Criteria:
-
Contacts and Locations| France | |
| CHU | Not yet recruiting |
| Brest, France, 29000 | |
| Contact: Pierre Yves Salaün, MD pierre-yves.salaun@chu-brest.fr | |
| Hôpital La tronche | Not yet 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 | |
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 10, 2011 |
| 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 Radio Immunotherapy Lutetium patient ≥ 18 years of age with CEA-positive SCLC who are in partial response or who failed at least two lines of standard radiation and/or chemotherapy |
Additional relevant MeSH terms:
|
Lung Neoplasms Small Cell Lung Carcinoma Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases |
Carcinoma, Bronchogenic Bronchial Neoplasms Antibodies Immunoglobulins Antibodies, Bispecific Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 23, 2013