Tumor Cell Vaccine for Patients Undergoing Surgery for Sarcomas, Melanomas, Germ Cell Tumors, or Malignancies That Have Metastasized to the Lungs, Pleura, or Mediastinum

NCT01313429 | Terminated Phase 1 FDA Drug

• 2 other identifiers: 11011111-C-0111
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Certain types of cancers, including sarcoma and melanoma, have specific antigens (protein molecules) on their surfaces. Research has shown that producing an immune reaction to these antigens may be able to keep tumors from growing by encouraging the immune system to destroy the tumor cells. By creating a vaccine that contains antigens similar to those found on the cancer cells, researchers hope to cause an immune reaction that targets the cancer cells. However, more research is needed to determine the safety and effectiveness of this type of vaccine treatment. Objectives: \- To determine whether a tumor cell vaccine, given to individuals who have had surgery to remove malignant tumors from the chest, can cause an immune reaction that will prevent the tumors from coming back. Eligibility: \- Individuals at least 18 years of age who have been diagnosed with cancer that has spread to the lungs, pleura, or mediastinum, and have recently had surgery to remove tumors in the chest. Design:

• Participants will be screened with a physical examination and medical history, as well as blood tests and imaging studies.
• Participants will have the option to have leukapheresis to collect white blood cells for studies on how the body is responding to the vaccine. Participants who agree to have this procedure will have it before the start of treatment and after the sixth and eighth vaccines.
• Seven days before the first vaccine, participants will receive the chemotherapy drugs celecoxib and cyclophosphamide to take twice a day at home.
• Participants will receive the experimental vaccine as an injection in the thigh or arm, and may receive it in two shots depending on how many cells are in each vaccine. Participants will receive a diary to monitor medication doses and side effects, as well as additional cyclophosphamide and celecoxib to take at home as directed by the study.
• Participants will have one vaccine every month for 6 months, and will have regular blood tests and imaging studies. After the sixth vaccine, participants who have successfully responded to the treatment will have two additional vaccines given 3 months apart.
• After the eighth vaccine, participants will have followup visits every 3 months for 1 year and then every 6 months for up to 4 years....

Conditions

Sarcoma; Melanoma; Epithelial Malignancies; Pleural Malignancies

Keywords

Metastatic Cancer; Cancer Vaccine; Immunotherapy; Adjuvant Therapy; Chest Metastases; Cancer; Melanoma; Lung Cancer; Sarcoma

Outcome Measures

Primary Outcomes (1)

• Summary of adverse events

  List of adverse event frequency

  30 days after last vaccine (up to 13 months)

Secondary Outcomes (2)

• Number and description of immunologic responses to a panel of CT antigens in vaccinated patients

  After last vaccine

• Paired t test analysis of difference between number and percentage of T reg cells at baseline and at treatment conclusion

  After last vaccine

Study Arms (1)

1

EXPERIMENTAL

tumor cell vaccine administered with chemotherapy

Drug: Cyclophosphamide; Biological: Allogenic tumor Cell Vaccine (K562); Drug: Celecoxib

Interventions

Cyclophosphamide DRUG

50 mg PO BID for 7 days prior to the first dose of vaccine and then on days 8 through 14, and 22 through 28 of each treatment cycle.

1

Allogenic tumor Cell Vaccine (K562) BIOLOGICAL

4 vaccines consisting of approximately 2.5E7 cells each will be delivered IM every 4 weeks for 6 months. If immune response is detected after first 6 vaccinations, 2 more may be given at 3 month intervals.

1

Celecoxib DRUG

400 mg PO BID for 7 days prior to the first dose of vaccine and then on days 1 through 28 of each vaccine cycle.

1

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with sarcomas, melanomas, germ cell tumors, or epithelial malignancies metastatic to the lungs, mediastinum, or pleura that have no clinical evidence of active disease (NED).
• Patients with active disease outside the thorax may be eligible for study once the extrathoracic disease is definitively treated by local modalities such as radiation, surgery, or radiofrequency ablation.
• Patients must have received or refused first line standard systemic therapy for their metastases (if applicable).
• Patients must be enrolled within 52 weeks following completion of metastasectomy and have shown no evidence of disease during that time.
• 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.
• Patients must have an ECOG performance status of 0 2.
• 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.
• 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).
• 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.

You may not qualify if:

• Patients who are initially rendered NED by surgical therapy but exhibit disease progression prior to initiation of vaccination will be excluded from the study.
• Patients requiring corticosteroids (other than inhaled) will be excluded.
• Patients with life expectancy less than 12 months will be excluded.
• 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.
• 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.
• Patients with other cardiac diseases may be excluded at the discretion of the PI following consultation with Cardiology consultants.
• Patients with any of the following pulmonary function abnormalities will be excluded: FEV, \< 30% predicted; DLCO \< 30% predicted (postbronchodilator); Oxygen Saturation less than 90% on room air.
• 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.
• Patients with active infections, including HIV, will be excluded, due to unknown effects of the vaccine on lymphoid precursors.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Quiros RM, Scott WJ. Surgical treatment of metastatic disease to the lung. Semin Oncol. 2008 Apr;35(2):134-46. doi: 10.1053/j.seminoncol.2007.12.010.

  PMID: 18396199 BACKGROUND

• ALEXANDER J, HAIGHT C. Pulmonary resection for solitary metastatic sarcomas and carcinomas. Surg Gynecol Obstet. 1947 Aug;85(2):129-46. No abstract available.

  PMID: 20253078 BACKGROUND

• Pastorino U, Buyse M, Friedel G, Ginsberg RJ, Girard P, Goldstraw P, Johnston M, McCormack P, Pass H, Putnam JB Jr; International Registry of Lung Metastases. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg. 1997 Jan;113(1):37-49. doi: 10.1016/s0022-5223(97)70397-0.

  PMID: 9011700 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Sarcoma; Melanoma; Neoplasm Metastasis; Neoplasms; Lung Neoplasms

Interventions

Cyclophosphamide; Celecoxib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Benzenesulfonamides; Sulfonamides; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• David S Schrump, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 10, 2011
• First Posted: March 11, 2011
• Study Start: March 4, 2011
• Primary Completion: February 26, 2020
• Study Completion: February 26, 2020
• Last Updated: March 3, 2020

Record last verified: 2020-03

Locations

US (1)