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Prostate CancerPhase 2STARVE-PCNCT02601014

Biomarker-Driven Therapy With Nivolumab and Ipilimumab in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer Expressing AR-V7

A Phase 2 study testing Ipilimumab, Nivolumab and Enzalutamide in people with Prostate Cancer and Recurrent Prostate Carcinoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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
Search all trials

Trial summary

This phase II trial studies how well nivolumab and ipilimumab work in treating patients with hormone-resistant prostate cancer that has spread to other places in the body and express androgen receptor-variant-7 (AR-V7). Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Ipilimumab, Nivolumab and Enzalutamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteUnited States
Study dates
15 Mar 2016to 6 Oct 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 or cytologically confirmed adenocarcinoma of the prostate
  • Metastatic disease as defined by two or more bone metastases confirmed by bone scintigraphy or radiographic soft tissue metastasis
  • Detectable circulating tumor cells (CTCs) with detectable AR-V7 splice-variant by reverse transcriptase (RT)-polymerase chain reaction (PCR)
  • For second cohort (amendment 1):
  • The most recent therapy must be enzalutamide and enzalutamide will be continued for study duration despite progressive disease. The minimum required dose of Enzalutamide at enrolment should be no less than 80 mg once daily.
  • Known castration-resistant disease, defined according to Prostate Cancer Working Group 2 (PCWG2) criteria as:
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  • Castrate serum testosterone level: =< 50 ng/dL (=< 1.7 nmol/L)
  • Subjects who have failed initial hormonal therapy, either by orchiectomy or by using a gonadotropin-releasing hormone (GnRH) agonist in combination with an anti-androgen, must first progress through antiandrogen withdrawal prior to being eligible; the minimum timeframe to document failure of anti-androgen withdrawal will be four weeks
  • Serum PSA progression defined as two consecutive increases in PSA over a previous reference value within 6 months of first study treatment, each measurement at least one week apart; serum PSA at screening >= 2 ng/mL OR
  • Documented bone lesions by the appearance of two or more new lesions by bone scintigraphy OR
  • Bidimensionally-measureable soft tissue metastatic lesion assessed by computed tomography (CT) or magnetic resonance imaging (MRI)
  • Karnofsky performance status (KPS): >= 70% within 14 days before start of study treatment (Eastern Cooperative Oncology Group [ECOG] =< 1)
  • Life expectancy: at least 6 months
  • White blood count (WBC) >= 2000/uL
  • Neutrophils >= 1500/uL
  • Platelets >= 100 x10^3/uL
  • Hemoglobin > 9.0 g/dL
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) >= 40 mL/min (if using the Cockcroft-Gault formula)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN
  • Total bilirubin =< 1.5 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Men who are sexually active with women of childbearing potential (WOCBP) must use any contraceptive method with a failure rate of less than 1% per year; men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product
  • WOCBP is defined as any female who has experienced menarche and has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
  • No evidence (within 5 years) of prior malignancies (except successfully treated basal cell or squamous cell carcinoma of the skin)
  • The subject is willing and able to comply with the protocol, and agrees to return to the hospital for follow-up visits and examination
  • The subject has been fully informed about the study and has signed the informed consent form and, where appropriate, Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information
  • NOTE: HIPAA authorization may be included in the informed consent or obtained separately

Who cannot join

  • Has received an investigational therapeutic drug within the last 4 weeks prior to start of study treatment, or is scheduled to receive one during the treatment period
  • Has received external radiotherapy within the last 4 weeks prior to start of study treatment
  • Previous therapy with antiandrogens within 4 weeks
  • Patients should be excluded if they have had prior systemic treatment with an anti-programmed cell death protein 1 (PD-1), anti-PD-L1, anti-programmed cell death 1 ligand 2 (PD-L2), anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways
  • Symptomatic metastatic disease with signs of rapid progression per investigator's clinical judgment
  • Concurrent use of other anticancer agents or treatments, with the following exceptions:
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  • Ongoing treatment with luteinizing hormone-releasing hormone (LHRH) agonists or antagonists, denosumab (Prolia) or bisphosphonate (eg, zoledronic acid) is allowed; ongoing treatment should be kept at a stable schedule; however, if medically required, a change of dose, compound, or both is allowed
  • Any treatment modalities involving major surgery within 4 weeks prior to the start of study treatment
  • Symptomatic nodal disease, i.e. scrotal, penile or leg edema (>= Common Terminology Criteria for Adverse Events [CTCAE] grade 3)
  • Patients are excluded if they have active brain metastases or leptomeningeal metastases; subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks after treatment is complete and within 28 days prior to the first dose of nivolumab administration; there must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration
  • Patients should be excluded if they have an active, known or suspected autoimmune disease (e.g. inflammatory bowel disease, rheumatoid arthritis, autoimmune hepatitis, lupus, celiac disease); subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
  • Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
  • Permitted therapies include topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption); physiologic replacement doses of systemic corticosteroids are permitted, even if > 10 mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of nonautoimmune conditions (e.g. delayed-type hypersensitivity reaction caused by contact allergen) is permitted
  • Drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen
  • Patients should be excluded if they have a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
  • Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Allergies and adverse drug reaction
  • History of allergy to study drug components
  • History of severe hypersensitivity reaction to any monoclonal antibody
  • Other primary tumor (other than castration-resistant prostate cancer [CRPC]) including hematological malignancy present within the last 5 years (except non-melanoma skin cancer or low-grade superficial bladder cancer)
  • Has imminent or established spinal cord compression based on clinical findings and/or MRI
  • Any other serious illness or medical condition that would, in the opinion of the investigator, make this protocol unreasonably hazardous, including, but not limited to:
  • Any uncontrolled infection
  • Cardiac failure NYHA (New York Heart Association) III or IV
  • Crohn's disease or ulcerative colitis
  • Bone marrow dysplasia
  • Known allergy to any of the compounds under investigation
  • Unmanageable fecal incontinence

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

Other trials in United States

About this study

Official title: Biomarker-Driven Phase-2 Study of Combined Immune Checkpoint Blockade for AR-V7-Expressing Metastatic Castration-Resistant Prostate Cancer (STARVE-PC)

This phase II trial studies how well nivolumab and ipilimumab work in treating patients with hormone-resistant prostate cancer that has spread to other places in the body and express androgen receptor-variant-7 (AR-V7). Tumor cells expressing AR-V7 has been shown to be resistant to hormone therapy and some chemotherapy in patients with prostate cancer. Biomarker-driven therapy, such as nivolumab and ipilimumab, may work by blocking key biomarkers or proteins that help tumor cells to escape the immune system surveillance and this may help the immune system to kill tumor cells that express AR-V7.

Keywords
Hormone-Resistant Prostate Cancer, Prostate Carcinoma Metastatic in the Bone
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 1 mg/kg IV

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, ONO-4538, Opdivo

    Given 3 mg/kg IV

  • EnzalutamideDrug

    Also called Xtandi

    given orally per standard of care

Study groups in NCT02601014
Study groupRoleWhat they receive
Nivolumab and ipilimumabExperimentalPatients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes every 3 weeks for 12 weeks. Patients then receive nivolumab IV over 60 minutes every 2 weeks for 36 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Ipilimumab; Biological: Nivolumab
Enzalutamide plus Nivolumab and IpilimumabExperimentalPatients will continue on standard of care enzalutamide, with the addition of nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes every 3 weeks for 12 weeks. Patients then receive nivolumab IV over 60 minutes every 2 weeks for 36 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Ipilimumab; Biological: Nivolumab; Drug: Enzalutamide

What is being measured

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

  1. Number of Participants With Change in PSA Response

    Number of participants with greater than 50% decline in PSA from start of treatment, sustained for >= 4 weeks, as defined by Prostate Cancer Working Group 2 (PCWG2) criteria.

    Measured: up to 3 years

Secondary outcomes (9)

  1. Durable Progression Free Survival (PFS)

    Number of participants with PFS >= 24 weeks. PFS is described as number of weeks from start of treatment until first evidence of clinical radiographic progression, or death.

    Measured: up to 3 years

  2. Number of Participants Experiencing Adverse Events

    Number of participants experiencing Grade 3-4 adverse events, Grade 3-4 immune-related AEs (irAEs), as defined by National Cancer Institute (NIH) CTCAE version 4.0

    Measured: up to 3 years

  3. Objective Response Rate (ORR)

    Number of participants with complete response (CR) or partial response (PR) in measurable soft tissue lesions, as defined by RECIST version 1.1

    Measured: up to 3 years

  4. Overall Survival

    Number of months alive after start of treatment.

    Measured: up to 3 years

  5. Progression Free Survival (PFS)

    Number of months from start of treatment until first evidence of progression, as defined by based on RECIST version 1.1 and PCWG2

    Measured: up to 3 years

  6. Number of Participants With Change in AR-V7 Expression

    Change in AR-V7 expression is defined as converting from AR-V7-positive to AR-V7-negative during treatment.

    Measured: up to 3 years

  7. PSA-PFS

    Number of months until >= 25% or >=2 ng/mL increase in PSA, as defined per PCWG2 criteria

    Measured: up to 3 years

  8. Response Duration in Patients With Objective Response

    Number of months from first evidence of response until progression.

    Measured: up to 12 months

  9. Number of Participants With Change in AR-V7 Expression as Expressed by AR-V7 to Full Length AR Ratio Converting From AR-V7-positive to -Negative With Changes in AR-V7 Expression

    Change in AR-V7 is described as converting from AR-V7-positive to -negative, expressed as a ratio of AR-V7 to full-length AR (AR-FL)

    Measured: up to 3 years

Timeline

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

  1. First posted10 Nov 2015 (estimated)
  2. Study start15 Mar 2016
  3. Primary completion3 Dec 2020
  4. Study completion6 Oct 2021

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02601014
Sponsor's protocol ID
J15119
Other IDs
NCI-2015-01325, J15119, IRB00070748
Acronym
STARVE-PC
Status last verified
Jan 2022
First submitted
21 Aug 2015
Last updated
3 Feb 2022
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Boudadi K, Suzman DL, Anagnostou V, Fu W, Luber B, Wang H, Niknafs N, White JR, Silberstein JL, Sullivan R, Dowling D, Harb R, Nirschl TR, Veeneman BA, Tomlins SA, Wang Y, Jendrisak A, Graf RP, Dittamore R, Carducci MA, Eisenberger MA, Haffner MC, Meeker AK, Eshleman JR, Luo J, Velculescu VE, Drake CG, Antonarakis ES. Ipilimumab plus nivolumab and DNA-repair defects in AR-V7-expressing metastatic prostate cancer. Oncotarget. 2018 Jun 19;9(47):28561-28571. doi: 10.18632/oncotarget.25564. eCollection 2018 Jun 19.

    PubMed 29983880

  • Shenderov E, Boudadi K, Fu W, Wang H, Sullivan R, Jordan A, Dowling D, Harb R, Schonhoft J, Jendrisak A, Carducci MA, Eisenberger MA, Eshleman JR, Luo J, Drake CG, Pardoll DM, Antonarakis ES. Nivolumab plus ipilimumab, with or without enzalutamide, in AR-V7-expressing metastatic castration-resistant prostate cancer: A phase-2 nonrandomized clinical trial. Prostate. 2021 May;81(6):326-338. doi: 10.1002/pros.24110. Epub 2021 Feb 26.

    PubMed 33636027

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ipilimumab, Nivolumab and Enzalutamide in people with Prostate Cancer and Recurrent Prostate Carcinoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 26 inclusion and 28 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 3 Feb 2022. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Change in PSA Response (time frame: up to 3 years). 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 NCT02601014, 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 3 Feb 2022.

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