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CART-PSMA-TGFβRDN Cells for Castrate-Resistant Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03089203
Recruitment Status : Recruiting
First Posted : March 24, 2017
Last Update Posted : April 11, 2023
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

Study Description
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Brief Summary:
This is a single center, single arm Phase I study to establish the safety and feasibility of intravenously administered lentivirally transduced dual PSMA-specific/ TGFβ-resistant CAR modified autologous T cells (CART-PSMA-TGFβRDN cells) in patients with metastatic castrate resistant prostate cancer.

Condition or disease Intervention/treatment Phase
Prostate Cancer Biological: CART-PSMA-TGFβRDN cells Drug: Cyclophosphamide Drug: Fludarabine Phase 1

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Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 19 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of CART-PSMA-TGFβRDN Cells in Patients With Advanced Castrate Resistant Prostate Cancer
Actual Study Start Date : March 8, 2017
Estimated Primary Completion Date : September 8, 2038
Estimated Study Completion Date : December 8, 2038

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort 1
CART-PSMA-TGFβRDN cells 1-3x10^7 Day 0
 Biological: CART-PSMA-TGFβRDN cells
autologous CAR T cells
Experimental: Cohort 2
CART-PSMA-TGFβRDN cells 1-3x10^8 Day 0
 Biological: CART-PSMA-TGFβRDN cells
autologous CAR T cells
Experimental: Cohort -3
CART-PSMA-TGFβRDN cells 1-3x10^7 Day 0
 Biological: CART-PSMA-TGFβRDN cells
autologous CAR T cells

Drug: Cyclophosphamide
300 mg/m2/day given over 3 days

Drug: Fludarabine
30 mg/m2/day given over 3 days
Experimental: Cohort 4
CART-PSMA-TGFβRDN cells 0.70-1.00 x 10^8 Day 0
 Biological: CART-PSMA-TGFβRDN cells
autologous CAR T cells

Drug: Cyclophosphamide
300 mg/m2/day given over 3 days

Drug: Fludarabine
30 mg/m2/day given over 3 days
Experimental: Cohort 3
CART-PSMA-TGFβRDN cells at the MTD (established by Cohorts 1-2) on day 0
 Biological: CART-PSMA-TGFβRDN cells
autologous CAR T cells

Drug: Cyclophosphamide
300 mg/m2/day given over 3 days

Drug: Fludarabine
30 mg/m2/day given over 3 days


Outcome Measures
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Primary Outcome Measures :
  1. Occurrence of study related adverse events, laboratory toxicities and clinical events that are possibly, likely, or definitely related to study participation. [ Time Frame: 15 years ]
    using CTCAE v 4.03

  2. Clinical feasibility is defined as the frequency of subjects enrolled on this protocol who do not receive CART-PSMA-TGFβRDN cells. [ Time Frame: 30 days ]
  3. Manufacturing feasibility is determined by the frequency of product release failures and the occurrence of dose failures (inability to meet target dose). [ Time Frame: 30 days ]

Secondary Outcome Measures :
  1. Assess the clinical anti-tumor effect of CART-PSMA-TGFβRDN cells by RECIST [ Time Frame: 6 months ]
    RECIST 1.1 criteria for soft tissue disease

  2. Assess the clinical anti-tumor effect of CART-PSMA-TGFβRDN cells by PCWG2 [ Time Frame: 6 months ]
    PCWG2 criteria for osseous disease

  3. Assess the clinical anti-tumor effect of CART-PSMA-TGFβRDN cells by serum PSA measurement [ Time Frame: 6 months ]
    serum PSA measurement

  4. Assess the clinical anti-tumor effect of CART-PSMA-TGFβRDN cells by overal survival (OS). [ Time Frame: 15 Years ]
  5. Assess the clinical anti-tumor effect of CART-PSMA-TGFβRDN cells by number of subjects with progression free survival (PFS). [ Time Frame: 15 Years ]

Eligibility Criteria
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Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Metastatic castrate resistant prostate cancer
  2. ≥10% tumor cells expressing PSMA as demonstrated by immunohistochemistry analysis on biopsied tissue. RETIRED WITH PROTOCOL VERSION 15
  3. Radiographic evidence of osseous metastatic disease and/or measurable, non-osseous metastatic disease (nodal or visceral)
  4. Patients ≥ 18 years of age
  5. ECOG performance status of 0 - 1

  6. Adequate organ function, as defined by:

    1. Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 60 cc/min
    2. Serum total bilirubin < 1.5x ULN
    3. Serum ALT/AST < 2x ULN

  7. Adequate hematologic reserve within 4 weeks of eligibility confirmation by physician-investigator as defined by:

    1. Hgb > 10 g/dl
    2. PLT > 100 k/ul
    3. ANC > 1.5 k/ul Note: Subjects must not be transfusion dependent

  8. Evidence of progressive castrate resistant prostate adenocarcinoma, as defined by:

    1. Castrate levels of testosterone (< 50 ng/ml) with or without the use of androgen-deprivation therapy AND
    2. Evidence of one of the following measures of progressive disease in the 12 weeks preceding eligibility confirmation by physician:

    i. soft tissue progression by RECIST 1.1 criteria ii. osseous disease progression with 2 or more new lesions on bone scan (as per PCWG2 criteria) iii. increase in serum PSA of at least 25% and an absolute increase of 2 ng/ml or more from nadir (as per PCWG2 criteria)

  9. Prior therapy with at least one standard initial therapy for the treatment of metastatic castrate resistant prostate cancer (i.e. docetaxel chemotherapy, 17α lyase inhibitor, or second-generation anti-androgen therapy)
  10. Provides written informed consent
  11. Subjects of reproductive potential must agree to use acceptable birth control methods

Exclusion Criteria:

  1. Treatment with immune checkpoint inhibitors and immunoconjugate therapies, including nivolumab, pembrolizumab, atezolizumab, ipilimumab, and/or durvalumab, within 2 months prior to eligibility confirmation by physician-investigator. Cancer vaccine therapies (such as Sipuleucel-T or PROSTVAC) are allowable as a prior line of therapy. Radium-223 is allowable as a prior line of therapy, provided laboratory complete blood counts meet all inclusion criteria as above, without transfusion support in the preceding 4 weeks.
  2. History of an active non-curative non-prostate primary malignancy within the prior 3 years
  3. Subjects with a rising PSA, but who have never had radiologic evidence of metastatic disease (i.e. 'biochemical recurrence') RETIRED WITH PROTOCOL VERSION 6
  4. Subjects who require the chronic use of systemic corticosteroid therapy. Patients may be on a low dose of steroids (≤10mg equivalent of prednisone).
  5. Subjects who have received > 4 prior therapies for the treatment of castrate resistant prostate cancer (excluding luteinizing hormone-releasing hormone agonists or antagonists, or first generation anti-androgen therapies). Note: Docetaxel or abiraterone/prednisone administered in the castration-sensitive setting will count as a prior line of therapy. RETIRED WITH PROTOCOL V13
  6. Subjects with Class III/IV cardiovascular disability according to the New York Heart Association Classification
  7. Subjects with symptomatic vertebral metastases affecting spinal cord function (as determined by clinical history, physical exam, or MRI imaging)
  8. Active autoimmune disease, including connective tissue disease, uveitis, inflammatory bowel disease, or multiple sclerosis; or a history of severe (as judged by the physician-investigator) autoimmune disease requiring prolonged immunosuppressive therapy
  9. Patients with ongoing or active infection.
  10. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
  11. Active hepatitis B, hepatitis C or HIV infection.
  12. Active medical condition that, in the opinion of the physician-investigator, would substantially increase the risk of uncontrollable CRS or CAR Neurotoxicity.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03089203


Contacts
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Contact: Naomi Haas, MD 855-216-0098 CancerTrials@emergingmed.com

Locations
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United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Naomi Haas, MD    855-216-0098    CancerTrials@emergingmed.com   
Sponsors and Collaborators
University of Pennsylvania
Investigators
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Principal Investigator: Naomi Haas, MD Universtiy of Pennsylvania
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT03089203    
Other Study ID Numbers: UPCC 32816, 826250
First Posted: March 24, 2017    Key Record Dates
Last Update Posted: April 11, 2023
Last Verified: April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Genital Diseases
Urogenital Diseases
Prostatic Diseases
Male Urogenital Diseases
Cyclophosphamide
 Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists