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

Primary Purpose

Sarcoma, Melanoma, Epithelial Malignancies

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Cyclophosphamide

Allogenic tumor Cell Vaccine (K562)

Celecoxib

About this trial

This is an interventional treatment trial for Sarcoma focused on measuring Metastatic Cancer, Cancer Vaccine, Immunotherapy, Adjuvant Therapy, Chest Metastases, Cancer, Melanoma, Lung Cancer, Sarcoma

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA:
1. 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).
2. 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.
3. Patients must have received or refused first line standard systemic therapy for their metastases (if applicable).
4. Patients must be enrolled within 52 weeks following completion of metastasectomy and have shown no evidence of disease during that time.
5. 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.
6. Patients must have an ECOG performance status of 0 2.
7. 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.
8. 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).
9. 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.
10. 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.
11. Patients must be aware of the neoplastic nature of their illnesses, the experimental nature of the therapy, alternative treatments, potential benefits, and risks.
12. Patients must be willing to practice birth control during and for four months following treatment.
13. Patients must be willing to sign an informed consent.

EXCLUSION CRITERIA:

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.

Sites / Locations

National Institutes of Health Clinical Center, 9000 Rockville Pike

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm Description

tumor cell vaccine administered with chemotherapy

Outcomes

Primary Outcome Measures

Summary of adverse events

List of adverse event frequency

Secondary Outcome Measures

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

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

Assessment of T regs in peripheral blood before and after initiation of CP/celecoxib treatment

Full Information

NCT ID

NCT01313429

First Posted

March 10, 2011

Last Updated

March 2, 2020

Sponsor

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01313429

Brief Title

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

Official Title

Adjuvant Allogeneic Tumor Cell Vaccine With Metronomic Oral Cyclophosphamide and Celecoxib in Patients Undergoing Resection of Sarcomas, Melanomas, Germ Cell Tumors, or Epithelial Malignancies Metastatic to Lungs, Pleura, or Mediastinum

Study Type

Interventional

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Terminated

Why Stopped

Per stopping rule if 12 patients underwent immune response analysis after 6 vaccinations and none developed a response, the protocol would stop accrual.

Study Start Date

March 4, 2011 (Actual)

Primary Completion Date

February 26, 2020 (Actual)

Study Completion Date

February 26, 2020 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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....

Detailed Description

Background: During recent years, the cancer-testis (CT) antigens (CTA) have emerged as attractive targets for cancer immunotherapy. Whereas malignancies of diverse histologies express a variety of CTAs, immune responses to these antigens appear uncommon in cancer patients, possibly due to low-level, heterogeneous antigen expression, as well as immunosuppressive regulatory T cells. Conceivably, vaccination of cancer patients with allogeneic tumor cells expressing high levels of multiple CTAs in combination with depletion of T regulatory cells will induce broad immunity to these antigens. In order to examine this issue, patients with sarcomas, melanomas, germ cell tumors, or epithelial malignancies metastatic to lungs, pleura or mediastinum will be vaccinated with irradiated K562 erythroleukemia cells expressing GM-CSF (K562-GM) following thoracic metastasectomy. Vaccines will be administered in conjunction with metronomic oral cyclophosphamide (50 mg PO BID x 7d q 14d), and celecoxib (400 mg PO BID). Serologic responses to a variety of recombinant CTAs will be assessed before and after vaccination. Primary Objectives: -To assess the safety of K562-GM allogeneic tumor cell vaccines in combination with oral metronomic cyclophosphamide and celecoxib in patients undergoing thoracic metastasectomy. Eligibility: Patients with histologically or cytologically proven sarcoma, melanoma, or epithelial malignancies metastatic to lungs, pleura or mediastinum who can be rendered no clinical evidence of active disease (NED). Patients must be 18 years or older with an ECOG performance status of 0 2, without evidence of unstable or decompensated myocardial disease. Patients must have adequate pulmonary reserve evidenced by FEV1 and DLCO equal to or greater than 30% predicted; pCO2 less than 50 mm Hg and pO2 greater than 60 mm Hg on room air ABG; and be on no immunosuppressive medications except inhaled corticosteroids at the time vaccination commences. Patients must have a platelet count greater than 100,000, an ANC equal to or greater than 1500 without transfusion or cytokine support, a normal PT, and adequate hepatic function as evidenced by a total bilirubin of <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) at the time vaccination commences. Design: Following recovery from thoracic metastasectomy, patients with NED or MRD will be vaccinated via deep subcutaneous injection with 1x10(8) irradiated K562 GM-tumor cells periodically over 6 months. Vaccines will be administered in conjunction with metronomic oral cyclophosphamide and celecoxib. Systemic toxicities, and immunologic response to therapy will be recorded. Pre and post vaccination serologic responses to a standard panel of CT antigens as well as cell mediated responses to epigenetically-modified autologous EBV-transformed B and autologous tumor cells (if available) will be assessed before and after vaccination. Numbers/percentages and function of T regulatory cells in peripheral blood will be assessed before, during, and after vaccinations. Patients will be followed in the clinic with routine staging scans until disease recurrence. As the exact set of comparisons and analyses to be performed will be determined following completion of the trial, and will be based on limited numbers of patients, the analyses will be considered exploratory and hypothesis generating rather than definitive. Approximately 25 patients will be accrued to this trial.

6. Conditions and Keywords

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

Sarcoma, Melanoma, Epithelial Malignancies, Pleural Malignancies

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

19 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

tumor cell vaccine administered with chemotherapy

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

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.

Intervention Type

Biological

Intervention Name(s)

Allogenic tumor Cell Vaccine (K562)

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Celecoxib

Intervention Description

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.

Primary Outcome Measure Information:

Title

Summary of adverse events

Description

List of adverse event frequency

Time Frame

30 days after last vaccine (up to 13 months)

Secondary Outcome Measure Information:

Title

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

Description

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

Time Frame

After last vaccine

Title

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

Description

Assessment of T regs in peripheral blood before and after initiation of CP/celecoxib treatment

Time Frame

After last vaccine

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

99 Years

Accepts Healthy Volunteers

Eligibility Criteria

INCLUSION CRITERIA: 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. 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 practice birth control during and for four months following treatment. Patients must be willing to sign an informed consent. EXCLUSION CRITERIA: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David S Schrump, M.D.

Organizational Affiliation

National Cancer Institute (NCI)

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Institutes of Health Clinical Center, 9000 Rockville Pike

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

18396199

Citation

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.

Results Reference

background

PubMed Identifier

20253078

Citation

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

Results Reference

background

PubMed Identifier

9011700

Citation

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.

Results Reference

background

Links:

URL

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2011-C-0111.html

Description

NIH Clinical Center Detailed Web Page

Learn more about this trial

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

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