Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Stage I-IIIB Non-Small Cell Lung Cancer After Completion of Radiation Therapy Alone or Combined Radiation Therapy and Chemotherapy

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00738452
First received: August 19, 2008
Last updated: August 7, 2013
Last verified: August 2013
  Purpose

RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as carboplatin, paclitaxel, cisplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiolabeled monoclonal antibodies can find tumor cells and carry tumor-killing substances to them without harming normal cells. Giving radiation therapy and combination chemotherapy together before radiolabeled monoclonal antibody therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of radiolabeled monoclonal antibody therapy when given after radiation therapy and combination chemotherapy in treating patients with stages I-IIIB non-small cell lung cancer.


Condition Intervention Phase
Lung Cancer
Other: high performance liquid chromatography
Other: pharmacological study
Procedure: radionuclide imaging
Procedure: single photon emission computed tomography
Radiation: radiation therapy
Radiation: yttrium Y 90 anti-CEA monoclonal antibody cT84.66
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Radioimmunotherapy (Y-90-Mx-DTPA-cT84.66) After Completion of Radiation Therapy Alone, or Radiation Therapy Plus Systemic Therapy in Unresectable or Medically Inoperable, Non-metastatic CEA-Producing Stage I-IIIB Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Maximum tolerated dose of yttrium Y 90 anti-CEA monoclonal antibody cT84.66 [ Time Frame: 6 weeks after treatment ] [ Designated as safety issue: Yes ]
  • Dose-limiting toxicity [ Time Frame: 6 weeks after treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: 6 months after treatment ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 6 months after treatment ] [ Designated as safety issue: No ]
  • Sites of recurrence [ Time Frame: 6 months after treatment ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: August 2008
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemo, monoclonal antibody therapy, radiation)
CHEMORADIOTHERAPY: Patients undergo external beam radiation therapy 5 days a week for 45 days. Beginning within 24 hours of the start of radiation therapy, patients receive paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36 OR cisplatin IV over 60 minutes on days 1, 8, 29, and 36 and etoposide IV over 60 minutes on days 1-5 and 29-33. CONSOLIDATION RADIOIMMUNOTHERAPY: Beginning 6-10 weeks after completion of chemoradiotherapy, patients with stable disease, partial response, or complete response receive a therapeutic dose of yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV. Treatment continues in the absence of disease progression or unacceptable toxicity.
Other: high performance liquid chromatography
Blood evaluation 0 minutes, 1 hour, 4 hours, 1 day, 2 days, 3-5 days and 6-7 days post start of antibody infusion. 24 hour urine sample evaluation daily for 5 consecutive days post antibody infusion.
Other: pharmacological study
Blood evaluation 0 minutes, 1 hour, 4 hours, 1 day, 2 days, 3-5 days and 6-7 days post start of antibody infusion. 24 hour urine sample evaluation daily for 5 consecutive days post antibody infusion.
Procedure: radionuclide imaging
Approximately 1-3 hours, 1 day, 2 days, 3-5 days and 6-7 days post infusion.
Procedure: single photon emission computed tomography
Approximately 2 days and 3-5 days post infusion
Radiation: radiation therapy
3-6 mCi Indium-111 labeled cT84.66(5mg) and dose escalation (depending on toxicities observed from previous dosages) from a starting dose of 8mCi/m2 Y-90-cT84.66.
Radiation: yttrium Y 90 anti-CEA monoclonal antibody cT84.66
Dose escalation (depending on toxicities observed from previous dosages) from a starting dose of 8mCi/m2 Y-90-cT84.66.

Detailed Description:

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and associated toxicities of intravenous yttrium-90 (90Y) chimeric T84.66 (cT84.66) anti-carcinoembryonic antigen (CEA) antibody targeted radiotherapy delivered after carboplatin/paclitaxel or cisplatin/etoposide and external beam radiotherapy in patients with CEA positive stage III unresectable or medically inoperable non-small cell lung cancer.

SECONDARY OBJECTIVES: I. To collect data on the biodistribution, clearance and metabolism of 90Y (yttrium-90) and 111In (indium-111) chimeric T84.66 administered intravenously. II. To collect data on radiation doses to whole body, normal organs, and tumor through serial nuclear imaging.

OUTLINE: This is a dose-escalation study of yttrium Y 90 anti-CEA monoclonal antibody cT84.66.

CHEMORADIOTHERAPY: Patients undergo external beam radiation therapy 5 days a week for 45 days. Beginning within 24 hours of the start of radiation therapy, patients receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36 OR cisplatin IV over 60 minutes on days 1, 8, 29, and 36 and etoposide IV over 60 minutes on days 1-5 and 29-33.

CONSOLIDATION RADIOIMMUNOTHERAPY: Beginning 6-10 weeks after completion of chemoradiotherapy, patients with stable disease, partial response, or complete response receive a therapeutic dose of yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 6 months

  Eligibility

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

Inclusion criteria:

  • Patients must be >= 18 years of age.
  • Patients must have a Karnofsky performance status of >= 60%.
  • Patients must have histological confirmation non-small cell lung cancer and must have tumors that produce CEA as documented by either immunohistochemistry or by an elevated serum CEA level.
  • Patients must have American Joint Committee on Cancer (AJCC) Version 7 Stage I-IIIB non small cell lung cancer (NSCLC) who are not a surgical candidate due to unresectability or medical inoperability.
  • Patients must have undergone radiation therapy alone, or radiation therapy plus systemic therapy (which includes chemotherapy or tyrosine kinase inhibitors) as treatment for their lung cancer; patients may receive up to two cycles of consolidative chemotherapy after radiation therapy +/- chemotherapy; this therapy must be completed within 6-12 weeks prior to starting treatment on this trial.
  • Patients must have had measurable or evaluable disease prior to receiving standard radiation therapy alone, or radiation therapy plus systemic therapy.
  • Patients must have no evidence of progressive disease (therefore, must have stable disease, partial response or complete response) to the therapy given prior to enrollment on this study.
  • No radiotherapy, immunotherapy, or chemotherapy within the last 5 years prior to the diagnosis of locally advanced NSCLC; prior adjuvant chemotherapy or tyrosine kinase inhibitor therapy for early stage, resected NSCLC is allowed as long as it was given > 12 months prior to the current diagnosis of locally advanced NSCLC.
  • Patients must demonstrate an forced expiratory volume in one second (FEV1) >= 0.9.
  • Adequate bone marrow function as evidenced by hemoglobin >= 10 gm %, WBC >= 3500/ul, an absolute granulocyte count of >= 1,500/mm3, and platelets >= 140,000/ul. Patients may be transfused to reach a hemoglobin >=10 gm %.
  • Patients must have a total bilirubin <= 1.5 mg/dL and liver transaminases no higher then 2 times the upper limit of normal.
  • Patients must have serum creatinine <= 1.5 x upper limit of normal (ULN) and a creatinine clearance >= 45 cc/min (based on Cockcroft Gault formula).
  • Patients must not have post-obstructive pneumonia or other serious infection.
  • If a patient has previously received murine or chimeric antibody, then serum anti-antibody testing must be negative.
  • Serum HIV testing and hepatitis B surface antigen and hepatitis C antibody testing must be negative.
  • Women of childbearing potential must have a negative serum pregnancy test prior to entry and while on study must be practicing an effective form of contraception.

Exclusion Criteria:

  • Patients with any nonmalignant intercurrent illness (example cardiovascular, pulmonary, or central nervous system disease) which is either poorly controlled with currently available treatment or which is of such severity that the investigators deem it unwise to enter the patient on protocol shall be ineligible.
  • Metastatic disease.
  • Malignant pleural effusion.
  • Patients that did not receive at least 50 Gy thoracic radiation during the course of radiation +/- systemic therapy.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00738452

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Jeffrey Y. Wong, MD Beckman Research Institute
Principal Investigator: Marianna Koczywas, MD Beckman Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00738452     History of Changes
Other Study ID Numbers: 07152, P30CA033572, CHNMC-07152, CDR0000611960, NCI-2010-01232, P01CA043904
Study First Received: August 19, 2008
Last Updated: August 7, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:
recurrent non-small cell lung cancer
stage II non-small cell lung cancer
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer

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

ClinicalTrials.gov processed this record on April 15, 2014