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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

Primary Purpose

Lung Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
high performance liquid chromatography
pharmacological study
radionuclide imaging
single photon emission computed tomography
radiation therapy
yttrium Y 90 anti-CEA monoclonal antibody cT84.66
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • City of Hope Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (chemo, monoclonal antibody therapy, radiation)

Arm Description

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.

Outcomes

Primary Outcome Measures

Maximum tolerated dose of yttrium Y 90 anti-CEA monoclonal antibody cT84.66
Dose-limiting toxicity

Secondary Outcome Measures

Progression-free survival
Overall survival
Sites of recurrence

Full Information

First Posted
August 19, 2008
Last Updated
February 9, 2018
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00738452
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2018
Overall Recruitment Status
Completed
Study Start Date
August 6, 2008 (undefined)
Primary Completion Date
February 7, 2018 (Actual)
Study Completion Date
February 7, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (chemo, monoclonal antibody therapy, radiation)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
high performance liquid chromatography
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
pharmacological study
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
radionuclide imaging
Intervention Description
Approximately 1-3 hours, 1 day, 2 days, 3-5 days and 6-7 days post infusion.
Intervention Type
Procedure
Intervention Name(s)
single photon emission computed tomography
Intervention Description
Approximately 2 days and 3-5 days post infusion
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
yttrium Y 90 anti-CEA monoclonal antibody cT84.66
Intervention Description
Dose escalation (depending on toxicities observed from previous dosages) from a starting dose of 8mCi/m2 Y-90-cT84.66.
Primary Outcome Measure Information:
Title
Maximum tolerated dose of yttrium Y 90 anti-CEA monoclonal antibody cT84.66
Time Frame
6 weeks after treatment
Title
Dose-limiting toxicity
Time Frame
6 weeks after treatment
Secondary Outcome Measure Information:
Title
Progression-free survival
Time Frame
6 months after treatment
Title
Overall survival
Time Frame
6 months after treatment
Title
Sites of recurrence
Time Frame
6 months after treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Y. Wong, MD
Organizational Affiliation
City of Hope Comprehensive Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Marianna Koczywas, MD
Organizational Affiliation
City of Hope Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010-3000
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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