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Recurrent Prostate CarcinomaPhase 1NCT00064129

Ipilimumab and Sargramostim in Treating Patients With Metastatic Prostate Cancer

A Phase 1 study testing Ipilimumab, Laboratory Biomarker Analysis and Pharmacological Study in people with Recurrent Prostate Carcinoma and Stage IV Prostate Cancer AJCC v7, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial is studying the side effects and best dose of ipilimumab when given with sargramostim in treating patients with metastatic prostate cancer. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Ipilimumab, Laboratory Biomarker Analysis and Pharmacological Study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
1 siteUnited States
Study dates
13 May 2003to 1 Oct 2012
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed prostate cancer
  • Metastatic disease
  • Progressive disease after prior androgen deprivation as defined by at least 1 of the following criteria:
  • Patients with measurable disease must have an increase of at least 20% in the sum of the longest diameter of target lesions OR the appearance of 1 or more new lesions
  • Patients with nonmeasurable disease must have a positive bone scan and a prostate-specific antigen (PSA) level of at least 5 ng/mL, which has risen on at least 2 successive occasions at least 2 weeks apart*
  • At least 1 PSA level must be obtained at least 4 weeks after flutamide (6 weeks after bicalutamide or nilutamide)
Show all 52Show fewer
  • Testosterone no greater than 50 ng/dL
  • Patients with no prior orchiectomy must continue luteinizing hormone-releasing hormone agonist therapy
  • No history or radiologic evidence of CNS metastases
  • Performance status - ECOG 0-2
  • At least 12 weeks
  • Absolute neutrophil count greater than 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 8 g/dL
  • Bilirubin less than 1.5 times upper limit of normal (ULN)
  • SGOT and SGPT no greater than 2.5 times ULN
  • Creatinine no greater than 1.5 times ULN
  • No significant cardiovascular disease
  • No New York Heart Association class III or IV congestive heart failure
  • No active angina pectoris
  • No myocardial infarction within the past 6 months
  • Not pregnant or nursing
  • Fertile patients must use effective contraception prior to, during, and for 3 months after study participation
  • No history of autoimmune disease including, but not limited to, any of the following:
  • Autoimmune hemolytic anemia
  • Ulcerative and hemorrhagic colitis
  • Endocrine disorders (e.g., thyroiditis, hyperthyroidism, hypothyroidism of immune etiology, autoimmune hypophysitis/hypopituitarism, or adrenal insufficiency)
  • Sarcoid granuloma
  • Myasthenia gravis
  • Polymyositis
  • Guillain-Barre syndrome
  • Systemic lupus erythematosus
  • Rheumatoid arthritis
  • Inflammatory bowel disease
  • No other medical or psychiatric illness that would preclude study participation or giving informed consent
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or stage I or II cancer currently in complete remission
  • No prior immunotherapy (e.g., vaccines or investigational)
  • No other concurrent colony-stimulating factors
  • No prior chemotherapy
  • No concurrent chemotherapy
  • See Disease Characteristics
  • At least 4 weeks since prior systemic corticosteroids
  • At least 4 weeks since other prior hormonal therapy, including megestrol and finasteride
  • No concurrent systemic steroid therapy except inhaled or topical steroids
  • No other concurrent hormonal therapy
  • Hormones administered for nondisease-related conditions (e.g., insulin for diabetes) allowed
  • At least 4 weeks since prior radiotherapy and recovered
  • More than 8 weeks since prior radiopharmaceuticals (e.g., strontium chloride Sr 89 and samarium Sm 153 lexidronam pentasodium)
  • Prior irradiation of a symptomatic lesion or one that may produce disability (e.g., unstable femur) allowed
  • No concurrent palliative radiotherapy
  • See Disease Characteristics
  • At least 4 weeks since prior herbal products known to decrease PSA levels (e.g., PC-SPES or saw palmetto)

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UCSF Medical Center-Mount Zion

    San Francisco, California, 94115

Other trials in United States

About this study

Official title: A Phase I Study of Repetitive Dosing of Anti-CTLA-4 Antibody (Ipilimumab) in Combination With GM-CSF in Patients With Metastatic, Androgen-Independent Prostate Cancer

This phase I trial is studying the side effects and best dose of ipilimumab when given with sargramostim in treating patients with metastatic prostate cancer. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Colony-stimulating factors, such as sargramostim, may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) (ipilimumab) administered with sargramostim (GM-CSF) in patients with metastatic androgen-independent prostate cancer. (Phase I) II. Determine the safety of this regimen in these patients. (Phase I) III. Evaluate the efficacy as measured by reduction in PSA associated with combining GM-CSF with CTLA-4 blockade with ipilimumab at a dosage of 3 mg/kg given monthly x 6 doses (d1 of courses 1-6). (Cohort Expansion)

SECONDARY OBJECTIVES:

  1. Determine the T-cell immunity and T-cell response in patients treated with this regimen. (Phase I) II. Determine the pharmacokinetics of MDX-010 in these patients. (Phase I) III. Determine the prostate-specific antigen and/or objective responses in patients treated with this regimen. (Phase I) IV. Determine the percentages of activated, naive, and memory T-cells. (Cohort Expansion) V. Determine the measurement of T-cell response to describe epitopes from prostate antigens including PSA, PSMA, and PAP. (Cohort Expansion) VI. Quantitate T-cell response to antigens in patients with relevant HLA allele using HLA*0201 tetramers. (Cohort Expansion) VII. Evaluate the toxicity of this regimen in these patients. (Cohort Expansion) VIII. Determine the initial efficacy as measured by reduction in PSA associated with combining GM-CSF with CTLA-4 blockade with ipilimumab at a dosage of 3 mg/kg given monthly x 6 doses (d1 of courses 1-6). (Cohort Expansion) IX. Determine objective response by post-therapy measurable disease changes using RECIST criteria. (Cohort Expansion)

OUTLINE: This is a multicenter, dose-escalation study of ipilimumab.

Patients receive ipilimumab intravenously (IV) over 90 minutes on day 1 and sargramostim (GM-CSF) subcutaneously (SC) on days 1-14. Treatment repeats every 28 days for 4-6 courses. GM-CSF continues beyond 4 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of ipilimumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Some patients undergo blood sample collection periodically for laboratory and pharmacokinetic studies. Samples are analyzed for human anti-human antibodies, IgG antibodies to ipilimumab semi-quantitative ELISA assay, and plasma concentrations of ipilimumab via quantitative ELISA assay.

Patients are followed at 30 days.

Being tested
Ipilimumab, Laboratory Biomarker Analysis, Pharmacological Study, Sargramostim
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • SargramostimBiological

    Also called 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine

    Given SC

Study groups in NCT00064129
Study groupRoleWhat they receive
Treatment (monoclonal antibody, colony-stimulating factors)ExperimentalPatients receive ipilimumab IV over 90 minutes on day 1 and sargramostim (GM-CSF) SC on days 1-14. Treatment repeats every 28 days for 4-6 courses. GM-CSF continues beyond 4 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of ipilimumab until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Some patients undergo blood sample collection periodically for laboratory and pharmacokinetic studies. Samples are analyzed for human anti-human antibodies, IgG antibodies to ipilimumab semi-quantitative ELISA assay, and plasma concentrations of ipilimumab via quantitative ELISA assay.
Receives: Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Sargramostim

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. MTD of the combination of ipilimumab with GM-CSF that results in < 33% DLT

    Graded according to the National Cancer Institute (NCI) common toxicity criteria, version 3.0. Results will be tabulated by dose cohort and overall for this trial. DLT is defined by any of the following that are attributable to therapy: any >= grade 4 toxicity, any ocular toxicity considered immune mediated and requiring systemic steroids, any grade 3 toxicity considered immune mediated that cannot be controlled with systemic steroids.

    Measured: Continuously

Secondary outcomes (5)

  1. Adaptive immunity

    Measured through peripheral blood collection. Three and four-color immunofluorescence and flow cytometric analysis will be employed to determine relative numbers of activated T cells. Specifically, percentages of T cells (CD3+, CD4+ or CD8+) expressing the activation markers HLA-DR, CD25 and CD69 will be determined. Also, percentages of naive (CD45RA+) and memory (CD45RO+) T cells will be determined.

    Measured: Baseline, days 1 and 14 of courses 1 and 2, day 1 of courses 3-6, and then day 1 of every other course throughout treatment

  2. PSA and/or objective response for measurable disease

    Evaluated according to Response Evaluation Criteria in Solid Tumors (RESIST) criteria. PSA Response will be evaluated according to the recommendations from National Cancer Institute PSA Working Group. 95% confidence interval will be provided.

    Measured: Day 1

  3. Safety of the regimen

    Graded according to the NCI common toxicity criteria, version 3.0.

    Measured: Continuously

  4. Anti-idiotype antibody (human anti-human antibodies [HAHA]) development

    A semi-quantitative ELISA assay will be used to detect IgG antibodies to Ipilimumab in the plasma samples.

    Measured: Baseline, before each ipilimumab infusion and 2 months after the last infusion of antibody

  5. Pharmacokinetic (PK) Studies

    Determined using a quantitative ELISA.

    Measured: Prior to and 60 minutes after all infusions, and at 1 and 2 months after the last ipilimumab infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jul 2003 (estimated)
  2. Study start13 May 2003
  3. Primary completion10 Jan 2011
  4. Study completion1 Oct 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00064129
Sponsor's protocol ID
NCI-2009-00036
Other IDs
NCI-2009-00036, UCSF-02558, CDR0000309054, NCI-6032, 02558, 6032
Status last verified
Jul 2020
First submitted
8 Jul 2003
Last updated
30 Jul 2020
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Cham J, Zhang L, Kwek S, Paciorek A, He T, Fong G, Oh DY, Fong L. Combination immunotherapy induces distinct T-cell repertoire responses when administered to patients with different malignancies. J Immunother Cancer. 2020 May;8(1):e000368. doi: 10.1136/jitc-2019-000368.

    PubMed 32376721

  • Kavanagh B, O'Brien S, Lee D, Hou Y, Weinberg V, Rini B, Allison JP, Small EJ, Fong L. CTLA4 blockade expands FoxP3+ regulatory and activated effector CD4+ T cells in a dose-dependent fashion. Blood. 2008 Aug 15;112(4):1175-83. doi: 10.1182/blood-2007-11-125435. Epub 2008 Jun 3.

    PubMed 18523152

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ipilimumab, Laboratory Biomarker Analysis and Pharmacological Study in people with Recurrent Prostate Carcinoma and Stage IV Prostate Cancer AJCC v7, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 52 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MTD of the combination of ipilimumab with GM-CSF that results in < 33% DLT (time frame: Continuously). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00064129, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2020.

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