Tumor Cell Vaccines and ISCOMATRIX With Chemotherapy After Tumor Removal

NCT01341496 | Terminated Phase 1

• 2 other identifiers: 11014811-C-0148
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- A tumor cell vaccine is an experimental cancer treatment. Cancer cells are collected from a patient and then used to develop a vaccine. The vaccine will produce an immune system response to help destroy other cancer cells in the body. Researchers are studying ways to improve these tumor cell vaccines. One way is to add an adjuvant. An adjuvant is a substance that brings about a stronger immune system response. ISCOMATRIX is an adjuvant that has been used safely in other clinical studies. But it has not been studied with certain tumor cell vaccines. Researchers want to find out whether a tumor cell vaccine with ISCOMATRIX, given along with cancer drug treatment, is a safe and effective way to slow or prevent tumor growth after tumor removal surgery. Objectives: \- To assess the safety and effectiveness of tumor cell vaccines given with ISCOMATRIX and drug therapy after tumor removal surgery. Eligibility: \- People at least 18 years of age who have had tumor cell vaccines developed from cells taken from surgically removed tumors. Design:

• Patients will be screened with a physical examination, medical history, blood and urine tests, and imaging studies.
• Patients will be treated with cyclophosphamide (once daily) and celecoxib (twice daily) for 7 days before the first vaccine dose.
• Patients will receive the tumor cell vaccine once a month for 6 months. They will continue to receive drug therapy throughout the vaccine treatment. Patients will be monitored with regular blood tests and imaging studies.
• After the first 6 months, patients who have an immune response to the vaccine will continue treatment with the vaccine and chemotherapy. They will also have regular blood tests and imaging studies. They will have this treatment for up to 24 months from the first vaccination or until they no longer have an immune response.
• Participants will have followup visits for up to 5 years after the first vaccination, or until the tumor returns.

Conditions

Sarcoma; Melanoma; Epithelial Malignancies; Pleural Malignancy

Keywords

Metastatic Cancer; Cancer Vaccine; Immunotherapy; Chest Metastases; Sarcoma; Melanoma

Outcome Measures

Primary Outcomes (1)

• tabulation and grade of observed patient toxicities attributed to the vaccine, and report of the fractions of patients who encounter these toxicities at the various grades

  5 years

Secondary Outcomes (2)

• Determine if 5 or greater of the first 20 vaccinated patients undergoing thoracic metastasectomy have successful tumor cell line development

  2-3 years

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

  7 years

Study Arms (1)

1

EXPERIMENTAL

autologous tumor vaccine plus chemotherapy

Biological: Epigenetically Modified Autologous Tumor; Drug: Cyclophosphamide; Drug: Celecoxib

Interventions

Epigenetically Modified Autologous Tumor BIOLOGICAL

5x 10\^7 autologous tumor cells emulsified in 0.5 mL ISCOMATRIX adjuvant will be administered IM every 4 weeks for 6 months

1

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 4 week treatment cycle

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 4 week 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 clinically evident or histologically proven sarcomas, melanomas, germ cell tumors, or epithelial malignancies metastatic to the lungs, mediastinum, or pleura who can be rendered no evidence of active disease (NED) following standard surgical therapy. Note: Patients with active disease outside the thorax may be eligible for the 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.
• Patients with no more than 3 intracranial metastases, which have been definitively treated by surgery or radiation therapy may be eligible for study provided there is no evidence of active disease for at least 2 months.
• 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.
• 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.
• 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.
• Patients must be aware of the neoplastic nature of their illnesses, the experimental nature of the therapy, alternative treatments, potential benefits, and risks.
• Patients must be willing to sign an informed consent and undergo resection of their malignancies at the NCI, to ensure vaccine development.
• Patients must have signed the Screening Consent.
• NCI Laboratory of Pathology confirmation of diagnosis of sarcomas, melanomas, germ cell tumors, or epithelial malignancies metastatic to the lungs, mediastinum, or pleura must have been obtained
• Patients who were initially rendered NED by surgical resection must remain NED at the time of treatment.
• Patients with no more than 3 intracranial metastases, which have been definitively treated by surgery or radiation therapy may be eligible for the study, provided there is no evidence of active disease for at least 2 months and no requirement for anticonvulsant therapy or steroids following treatment.
• Patients must have an ECOG performance status of 0 2.
• Patients must have evidence of adequate bone marrow reserve, hepatic and renal function as evidenced by the following laboratory parameters:

You may not qualify if:

• 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 infarctionwithin 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 (post-bronchodilator); pO2 \< 60% or pCO2 (Bullet) 50 on room air arterial blood gas.
• 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

• Klapper JA, Davis JL, Ripley RT, Smith FO, Nguyen DM, Kwong KF, Mercedes L, Kemp CD, Mathur A, White DE, Dudley ME, Wunderlich JR, Rosenberg SA, Schrump DS. Thoracic metastasectomy for adoptive immunotherapy of melanoma: a single-institution experience. J Thorac Cardiovasc Surg. 2010 Dec;140(6):1276-82. doi: 10.1016/j.jtcvs.2010.05.020. Epub 2010 Jul 2.

  PMID: 20584535 BACKGROUND

MeSH Terms

Conditions

Sarcoma; Melanoma; Neoplasm Metastasis

Interventions

Cyclophosphamide; Celecoxib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; 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

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
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2011
• First Posted: April 25, 2011
• Study Start: April 18, 2011
• Primary Completion: May 12, 2016
• Study Completion: July 21, 2016
• Last Updated: July 5, 2018

Record last verified: 2016-07-21

Locations

US (1)