Pilot Study of Allogeneic Tumor Cell Vaccine With Metronomic Oral Cyclophosphamide and Celecoxib in Patients Undergoing Resection of Lung and Esophageal Cancers, Thymic Neoplasms, and Malignant Pleural Mesotheliomas

• ClinicalTrials.gov Identifier: NCT01143545
• Recruitment Status: Completed
• First Posted: June 14, 2010
• Last Update Posted: June 19, 2019
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Study Description

Brief Summary:

Background:

- Certain types of lung, esophageal, or thymic cancers and mesotheliomas have specific antigens (protein molecules) on their surfaces. Research studies have shown that giving a vaccine that contains antigens similar to these may cause an immune response, which may keep tumors from growing. Researchers are also interested in determining whether the chemotherapy drug cyclophosphamide and the anti-inflammatory drug celecoxib may help the vaccine work better, particularly in patients with lung cancer.

Objectives:

- To evaluate the safety and effectiveness of tumor cell vaccines in combination with cyclophosphamide and celecoxib in patients with cancers involving the chest.

Eligibility:

- Individuals at least 18 years of age who have had surgery for small cell or non-small cell lung cancer, esophageal cancer, thymoma or thymic carcinoma, and malignant pleural mesothelioma.

Design:

• Following recovery from surgery, chemotherapy, or radiation, participants will have leukapheresis to collect lymphocytes (white blood cells) for testing.
• Participants will receive celecoxib and cyclophosphamide to take twice a day at home, 7 days before the vaccine.
• Participants will have the vaccine in the clinical center (one or two shots per month for 6 months), and will stay in the clinic for about 4 hours after the vaccine. Participants will keep a diary at home of any side effects from the vaccine, and will continue to take cyclophosphamide and celecoxib.
• One month after the sixth vaccine, participants will provide another blood sample for testing, and if the tests are satisfactory will return to the clinic every 3 months for 2 additional vaccines.
• Participants will return to clinic for follow-up physical examinations, lab tests, and scans every 3 months for 2 years and then every 6 months for up to 3 years.

Condition or disease	Intervention/treatment	Phase
Lung Cancer; Esophageal Cancer; Malignant Pleural Mesothelioma; Sarcoma; Thymic Carcinoma	Biological: Allogeneic Tumor Cell Vaccine (K562); Drug: Celecoxib; Drug: cyclophosphamide	Phase 1

  Show Detailed Description

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Allogeneic Tumor Cell Vaccine With Metronomic Oral Cyclophosphamide and Celecoxib as Adjuvant Therapy for Lung and Esophageal Cancers, Thymic Neoplasms, Thoracic Sarcomas, and Malignant Pleural Mesotheliomas
• Study Start Date: May 31, 2010
• Actual Primary Completion Date: February 9, 2015
• Actual Study Completion Date: March 19, 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; Allogeneic tumor cell vaccine + chemotherapy	Biological: Allogeneic Tumor Cell Vaccine (K562); Subcutaneous injection monthly for 6 months; Drug: Celecoxib; 400 g po bid; Drug: cyclophosphamide; 50 mg po bid

Outcome Measures

Primary Outcome Measures :

1. Tabulation of toxicity type and grade [ Time Frame: 2 years ]
   If 25 patients are enrolled and the true probability of a grade 3 or worse toxicity (of any sort) were 20%, then the probability of having 4 or more patients with this occurring is 76.6%. On the other hand, if the combination was very safe and the true probability of a grade 3 or worse toxicity was 5%, then the probability of having 4 or more patients with this occurring would be 3.4%. Thus, if 25 patients were treated, the combination may be considered to have potentially lower safety than tolerable if 4 or more patients experience grade 3 or worse toxicity.

Secondary Outcome Measures :

1. To ascertain if K526-GM vaccines induce immunity to CT antigens commonly expressed in thoracic malignancies. [ Time Frame: 2 years ]
   Perform exploratory analyses which investigate immunologic responses to a panel of CT antigens in vaccinated patients.
2. To determine if metronomic oral CP and celecoxib reduce the number, percentage and function of CD4+ CD25+ Fox P3+ regulatory T cells (T reg) in peripheral blood of thoracic oncology patients. [ Time Frame: 2 years ]
   Measure T regulatory cells at baseline and at the conclusion of treatment. The difference, or the relative difference, in the values at the two time points will be obtained, and tested to determine if the difference is equal to zero. If a paired t-test is able to be used, with at least 20 evaluable patients, there is 81% power to detect a change equal to 3/4ths of a standard deviation of the change at the two-sided 0.025 significance level.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

-INCLUSION CRITERIA:

1. Patients with primary small cell or non-small cell lung cancer, esophageal cancer, thymoma, thymic carcinoma, primary sarcoma of the chest, or pleural mesothelioma with no evidence of disease (NED) or minimal residual disease (MRD) in the primary site following standard multi-modality therapy.
2. Patients must be evaluated within 52 weeks following completion of standard therapy and have shown no evidence of disease during that time.
3. Patients with intracranial metastases, which have been treated by surgery or radiation therapy may be eligible for study provided there is no evidence of active disease and no requirement for anticonvulsant therapy or steroids following treatment.
4. Patients must have an ECOG performance status of 0 - 2.
5. Patients must be 18 years of age or older due to the unknown effects of immunologic responses to germ cell-restricted gene products during childhood and adolescent development.

6. Patients must have evidence of adequate bone marrow reserve, hepatic and renal function as evidenced by the following laboratory parameters:

   • Absolute neutrophil count greater than 1500/mm^3
   • Platelet count greater than 100,000/mm^3
   • Hemoglobin greater than 8g/dl (patients may receive transfusions to meet this parameter)
   • PT within 2 seconds of the ULN
   • Total bilirubin <1.5 times upper limits of normal
   • Serum creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater than 70 ml/min/1.73m(2).
7. Seronegative for HIV antibody. Note: The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus may be less responsive to the experimental treatment.
8. Seronegative for active hepatitis B, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
9. Patients must be willing to practice birth control during and for four months following treatment.
10. Patients must be willing to sign an informed consent.
11. Patients must be willing to sign an informed consent.

EXCLUSION CRITERIA:

1. Patients who are initially rendered NED or MRD by combined modality therapy but exhibit disease progression prior to initiation of vaccination will be excluded from the study.
2. Patients who will have received more than two systemic cytotoxic treatment regimens for their thoracic malignancy by the time vaccination commences will be excluded.
3. Patients requiring corticosteroids (other than inhaled) will be excluded.
4. Patients with life expectancy less than 12 months will be excluded.
5. Patients receiving warfarin anticoagulation, who cannot be transferred to other agents such as enoxaparin or dabigatran, and for whom anticoagulants cannot be held for up to 24 hours will be excluded.
6. Patients with uncontrolled hypertension (>160/95), unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated CHF (>NYHA Class II), or myocardial infarction within 6 months of study will be excluded.
7. Patients with other cardiac diseases may be excluded at the discretion of the PI following consultation with Cardiology consultants.
8. Patients with any of the following pulmonary function abnormalities will be excluded: FEV, < 30% predicted; DLCO < 30% predicted (post-bronchodilator); Oxygen Saturation less than 90% on room air.
9. Pregnant and/or lactating women will be excluded due to the unknown, potentially harmful effects of immune response to CT-X antigens and stem cell proteins that may be expressed in placenta, fetus, and neonates.
10. Patients with active infections, including HIV, will be excluded, due to unknown effects of the vaccine on lymphoid precursors.
11. Patients with any type of primary immunodeficiencies will be excluded from the study.

Contacts and Locations

Locations

United States, Maryland

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

• Principal Investigator: David S Schrump, M.D.; National Cancer Institute (NCI)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

Publications:

Kelsen DP, Winter KA, Gunderson LL, Mortimer J, Estes NC, Haller DG, Ajani JA, Kocha W, Minsky BD, Roth JA, Willett CG; Radiation Therapy Oncology Group; USA Intergroup. Long-term results of RTOG trial 8911 (USA Intergroup 113): a random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer. J Clin Oncol. 2007 Aug 20;25(24):3719-25.

Manegold C, Thatcher N. Survival improvement in thoracic cancer: progress from the last decade and beyond. Lung Cancer. 2007 Aug;57 Suppl 2:S3-5.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01143545 History of Changes
• Other Study ID Numbers: 100138; 10-C-0138
• First Posted: June 14, 2010
• Last Update Posted: June 19, 2019
• Last Verified: December 14, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):

Cancer Vaccine; Immunotherapy; Adjuvant Therapy; Surgical Intervention; Lung Cancer; Esophageal Cancer; Thymic Carcinoma; Malignant Pleural Mesothelioma

Additional relevant MeSH terms:

Sarcoma; Esophageal Neoplasms; Mesothelioma; Thymoma; Thymus Neoplasms; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Thoracic Neoplasms; Neoplasms by Site; Neoplasms, Connective and Soft Tissue; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Adenoma; Neoplasms, Mesothelial; Neoplasms, Complex and Mixed; Lymphatic Diseases; Celecoxib; Cyclophosphamide; Vaccines; Immunologic Factors; Physiological Effects of Drugs; Immunosuppressive Agents; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents