Trial record 2 of 11 for:    Sarcoidosis | Open Studies | NIH, U.S. Fed

SS1P and Pentostatin Plus Cyclophosphamide for Mesothelioma

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01362790
First received: May 27, 2011
Last updated: May 16, 2014
Last verified: December 2013
  Purpose

Background:

  • Malignant mesothelioma is a form of cancer that develops on the protective lining that covers the body s internal organs. It most often occurs on the lining of the lungs and chest wall or the lining of the abdomen. There is no known cure for malignant mesothelioma, so researchers are searching for new ways to treat it.
  • Mesothelin is a protein that is found in mesothelioma and other types of cancer cells. An experimental cancer drug called SS1P is designed to attack cells that have mesothelin while leaving healthy cells alone. Researchers want to test how effective SS1P is when it is given with pentostatin and cyclophosphamide. These drugs help suppress the immune system and may make the SS1P more effective.

Objectives:

- To study the effectiveness of SS1P plus two drugs that suppress the immune system to treat malignant mesothelioma.

Eligibility:

- Individuals at least 18 years of age who have malignant mesothelioma in the chest or abdomen.

Design:

  • Participants will be screened with a physical exam, medical history, and blood tests. They will also have imaging studies.
  • The first treatment cycle will last 30 days. Up to three 21-day cycles of treatment will follow.
  • In the first cycle, participants will have pentostatin on days 1, 5, and 9. They will have cyclophosphamide on days 1 through 12. They will have SS1P on days 10, 12, and 14.
  • On the next three cycles, participants will have pentostatin on day 1.They will have cyclophosphamide on days 1 through 4. They will have SS1P on days 2, 4, and 6.
  • Participants will have frequent blood tests and other studies. They will receive all four cycles of treatment as long as there are no severe side effects.
  • Participants will have regular followup visits as directed by the study doctors.

Condition Intervention Phase
Mesothelioma
Drug: Pentostatin
Drug: Cyclophosphamide
Drug: SS1P
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot/ Phase II Study of Pentostatin Plus Cyclophosphamide Immune Depletion to Decrease Immunogenicity of SS1P in Patients With Mesothelioma

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Determining safety, tolerability, and feasibility of a conditioning regimen of pentostatin and cyclophosphamide in combination with SS1(dsFv)PE38
  • Monitoring antibody formation to SS1(dsFv)PE38 and assessing the impact of the conditioning regimen

Secondary Outcome Measures:
  • To evaluate the objective tumor response, duration of response and progression-free survival
  • To investigate the potential of soluble mesothelin levels to predict any therapeutic response

Estimated Enrollment: 47
Study Start Date: May 2011
Intervention Details:
    Drug: Pentostatin
    N/A
    Drug: Cyclophosphamide
    N/A
    Drug: SS1P
    N/A
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

-INCLUSION CRITERIA:

  1. Subjects must have histologically confirmed epithelial or biphasic mesothelioma not amenable to potentially curative surgical resection. However, patients with biphasic tumors that have a greater than or equal to 50 percent sarcomatoid component will be excluded. The diagnosis will be confirmed by the Laboratory of Pathology / CCR / NCI.
  2. Patients must have had at least one prior chemotherapy regimen, with the FDA-approved regimen of a platinum-based therapy in combination with pemetrexed being preferred unless there was a specific contraindication for an individual patient. There is no limit to the number of prior chemotherapy regimens received.
  3. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan. See Section 11 for the evaluation of measurable disease.
  4. Patients must not have had major surgery, radiation therapy, chemotherapy, biologic therapy (including any investigational agents), or hormonal therapy (other than replacement), within 4 weeks prior to entering the study and must have evidence of stable or progressive disease to be eligible.
  5. Age greater than or equal to 18 years. Since mesothelioma is extremely rare in children, they are excluded from this study.
  6. Life expectancy of greater than 3 months.
  7. Performance status (ECOG) less than or equal to 1 (Appendix A).
  8. Patients must have adequate organ and marrow function (as defined below).

    • leukocytes greater than or equal to 3,000/mm(3)
    • absolute neutrophil count greater than or equal to 1,500/mm(3)
    • hemoglobin greater than or equal to 9 g/dL
    • platelets greater than or equal to 90,000/ mm(3)
    • total bilirubin less than or equal to 1.5 times institutional upper limit of normal (ULN)
    • AST(SGOT)/ALT(SGPT) less than or equal to 3 times institutional ULN (5 times if LFT elevations due to liver metastases)
    • creatinine less than or equal to 1.5 times institutional ULN

    OR

    - creatinine clearance greater than or equal to 45 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal, obtained through calculated or measured Creatinine Clearance

    Patients may be transfused to obtain a hemoglobin of greater than or equal to 9 g/Dl.

  9. The effects of SS1(dsFv)PE38, pentostatin, and cyclophosphamide on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) for the duration of study therapy and for 3 months after the last dose of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. While hormonal methods of birth control are effective, we ask that female patients who are participating in the study cease hormonal forms of birth control, as these methods of birth control (birth control pills, injections, or implants) may affect the study drug. Patients must be off hormonal forms of birth control for at least 4 weeks prior to initiating the study.
  10. Ability to comply with intravenous administration schedule, and the ability to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

  1. Patients with symptomatic brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, patients who have had treatment for their brain metastases and whose brain metastatic disease status has remained stable for at least 4-6 weeks without steroids may be enrolled at the discretion of the principal investigator.
  2. Uncontrolled medical illness including, but not limited to, ongoing or uncontrolled, symptomatic congestive heart failure (AHA Class II or worse), uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  3. HIV positive patients will be excluded due to a theoretical concern that the degree of immune suppression associated with the treatment may result in progression of HIV infection.
  4. Patients with Hepatitis B and C will be excluded.
  5. Serum neutralization antibody assay shows greater than or equal to 75 percent neutralization of the SS1 (dsFv) PE38 activity at 200 ng/ml.
  6. Patients may not be receiving any other investigational agents.
  7. History of another invasive malignancy in the last two years. Adequately treated noninvasive, non-melanoma skin cancers as well as in situ carcinoma of the cervix will be allowed.
  8. Prior treatment with drugs of the immunotoxin class.
  9. Patients with tumor amenable to potentially curative therapy as assessed by the investigator. In patients with peritoneal mesothelioma who have had no prior surgery, a surgical consultation will be obtained to see if the patient is a candidate for debulking surgery.
  10. Pregnant women are excluded from this study because SS1(dsFv)PE38, pentostatin, and cyclophosphamide have the potential for teratogenic or abortifacient effects. The agents in the trial may also potentially be secreted in milk and therefore breastfeeding women should be excluded. Because of the potential of teratogenic or abortifacient effects women of childbearing potential and men must agree to use adequate contraception (barrier methods) before, during the study and for a period of 3 months after the last dose of the investigational agent.
  11. History of allergic reactions attributed to compounds of similar chemical or biologic composition to SS1(dsFv)PE38.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01362790

Contacts
Contact: Yvonne D Mallory, R.N. (301) 402-0255 malloryy@mail.nih.gov
Contact: Raffit Hassan, M.D. (301) 451-8742 rh276q@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
Sponsors and Collaborators
Investigators
Principal Investigator: Raffit Hassan, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT01362790     History of Changes
Other Study ID Numbers: 110160, 11-C-0160
Study First Received: May 27, 2011
Last Updated: May 16, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Immune Therapy
Immunotoxin
T-Cell Depletion
Mesothelioma

Additional relevant MeSH terms:
Mesothelioma
Neoplasms, Mesothelial
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Cyclophosphamide
Pentostatin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Adenosine Deaminase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014