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A Study of Chemoimmunotherapy for the Treatment of Men With Neuroendocrine or Aggressive Variant Metastatic Prostate Cancer (CHAMP)

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ClinicalTrials.gov Identifier: NCT04709276
Recruitment Status : Recruiting
First Posted : January 14, 2021
Last Update Posted : June 10, 2021
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Andrew J. Armstrong, MD, Duke University

Brief Summary:
The purpose of this study is to evaluate the safety and efficacy of a combination of nivolumab, ipilimumab, cabazitaxel and carboplatin in men with neuroendocrine prostate cancer (NEPC) or other aggressive variants of prostate cancer (AVPC). This study will also investigate biomarkers to gain a better understanding of how the drug combination of nivolumab, ipilimumab, cabazitaxel and carboplatin affects these types of prostate cancer and the immune system. Eligible subjects will receive up to 10 cycles of nivolumab, ipilimumab, carboplatin and cabazitaxel followed by maintenance nivolumab and ipilimumab. Subjects may continue receiving study drugs until cancer progression, severe toxicity, withdrawal of consent, 3 years from the initial dose of study drugs or study termination, whichever occurs earlier. Subjects will be followed for 3 years from the initial dose of study drugs.

Condition or disease Intervention/treatment Phase
Metastatic Prostate Neuroendocrine Carcinoma Metastatic Prostate Cancer Drug: Nivolumab Drug: Ipilimumab Drug: Carboplatin Drug: Cabazitaxel Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 43 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Single Arm Study of Chemoimmunotherapy for the Treatment of Men With Neuroendocrine or Aggressive Variant Metastatic Prostate Cancer (CHAMP)
Actual Study Start Date : June 7, 2021
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : June 2027


Arm Intervention/treatment
Experimental: Neuroendocrine Prostate Cancer (NEPC) or Aggressive Variant Prostate Cancer (AVPC)

Subjects with neuroendocrine prostate cancer (NEPC) or aggressive variant prostate cancer (AVPC) will receive a combination of nivolumab, ipilimumab, carboplatin and cabazitaxel for up to 10 cycles of 21 days each. After carboplatin and cabazitaxel are discontinued, a combination of nivolumab and ipilimumab will be administered.

Nivolumab will be administered intravenously at a dose of 360 mg every 3 weeks.

Ipilimumab will be administered intravenously at a dose of 1 mg/kg every 6 weeks.

Carboplatin will be administered intravenously at a dose of AUC 4 mg/ml per minute.

Cabazitaxel will be administered intravenously at a dose of 20 or 25 mg/m2.

Drug: Nivolumab
360 mg intravenously every 3 weeks
Other Names:
  • BMS-936558
  • MDX1106
  • ONO-4538

Drug: Ipilimumab
1 mg/kg intravenously every 6 weeks
Other Names:
  • BMS-734016
  • MDX010
  • MDX-CTLA4

Drug: Carboplatin

AUC 4 mg/ml per minute intravenously every 3 weeks for up to 10 cycles.

Subjects will also receive granulocyte-colony stimulating factor (G-CSF) therapy while receiving carboplatin.


Drug: Cabazitaxel

20 or 25 mg/m2 intravenously every 3 weeks for up to 10 cycles.

Subjects will also take prednisone by mouth at a dose of 10 mg daily and receive granulocyte-colony stimulating factor (G-CSF) therapy while receiving cabazitaxel.

Other Name: JEVTANA




Primary Outcome Measures :
  1. Proportion of subjects who are progression-free and alive (progression-free survival) at 6 months [ Time Frame: 6 months ]
    Progression-free survival will be determined by immune modified or Prostate Cancer Working Group 3 (PCWG3)-defined RECIST 1.1 radiographic criteria.


Secondary Outcome Measures :
  1. Proportion of subjects who are progression-free and alive (progression-free survival) at 12 months [ Time Frame: 12 months ]
    Progression-free survival will be determined by immune modified or PCWG3-defined RECIST 1.1 radiographic criteria.

  2. Proportion of subjects who are progression-free and alive (progression-free survival) and without severe toxicity leading to treatment discontinuation at 6 and 12 months [ Time Frame: 6 and 12 months ]
    Progression-free survival will be determined by immune modified or PCWG3-defined RECIST 1.1 radiographic criteria.

  3. Overall survival [ Time Frame: 6, 12 and 24 months ]
  4. Median overall survival [ Time Frame: Through study completion (up to 3 years) ]
  5. Describe the radiographic progression free survival (rPFS) [ Time Frame: Through study completion (up to 3 years) ]
    Radiographic progression free survival will be determined by immune modified PCWG3-defined RECIST criteria.

  6. Describe the best radiographic response by immune modified PCWG3-defined RECIST radiographic response. [ Time Frame: Through study completion (up to 3 years) ]
    Radiographic response will be determined by immune modified PCWG3-defined RECIST criteria.

  7. Describe the toxicities of nivolumab, and ipilimumab in combination with carboplatin and cabazitaxel using NCI CTC v5.0. [ Time Frame: Through discontinuation of carboplatin and cabazitaxel dosing (up to 30 weeks) ]
    The toxicity and safety will be graded using NCI CTCAE v5.0.

  8. Describe the changes in the blood-based biomarker Prostate-Specific Antigen (PSA) over time [ Time Frame: Through discontinuation of study drugs (up to 3 years) ]
    PSA

  9. Describe the changes in the blood-based biomarker chromogranin-A over time [ Time Frame: Through discontinuation of study drugs (up to 3 years) ]
    chromogranin-A

  10. Describe the changes in the blood-based biomarker carcinoembryonic antigen (CEA) over time [ Time Frame: Through discontinuation of study drugs (up to 3 years) ]
    CEA

  11. Describe the changes in the blood-based biomarker lactate dehydrogenase (LDH) over time [ Time Frame: Through discontinuation of study drugs (up to 3 years) ]
    LDH

  12. Describe the changes in the blood-based biomarker alkaline phosphatase over time [ Time Frame: Through discontinuation of study drugs (up to 3 years) ]
    alkaline phosphatase



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
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Neuroendocrine-like prostate cancer, based on histology OR based on clinical presentation as defined by meeting one of the two below criteria. All subjects must submit their primary tumor or metastatic biopsy pathology specimens to the Duke Cancer Institute where they will be centrally reviewed by Duke Pathology. Central Duke pathologic review is not required for screening but rather for confirmation of histologic subtype. Local pathologic review is sufficient for eligibility determination.

    1. Criterion 1: Presence of 1 of 3 histologically proven diagnoses: 1) Primary small cell carcinoma of the prostate, defined by classic histologic features such as small tumor cells with scanty cytoplasm, darkly stained nuclei with homogeneous chromatin pattern. The tumor cells do not form glandular structure but grow as solid sheets with frequent mitotic figures and necrosis; 2) Intermediate atypical carcinoma of the prostate, which has histologic features distinct from small cell carcinoma or adenocarcinoma. The tumor grows as solid sheets or vague glandular structures. The tumor cells have moderate amounts of cytoplasm and centrally located, round and regular nuclei with fine, granular and homogeneous chromatin. Mitosis and necrosis are absent; 3) mixed histology tumors of the prostate, containing both adenocarcinoma and neuroendocrine or small cell components.
    2. Criterion 2: Presence of histologically proven adenocarcinoma of the prostate without any sign of neuroendocrine or small cell histology that is radiographically progressing despite castrate levels of testosterone (<50 ng/mL) with the following poor risk features:

    i. Prior progression despite therapy with either abiraterone acetate and/or enzalutamide.

    ii. At least one of the following: 1) Visceral metastases; 3) Bulky lymphadenopathy or pelvic mass (>5 cm); 4) Low PSA (<10 ng/mL) with high volume (>20) bone metastases; 5) Short interval (<6mo) to CRPC following initiation of hormonal therapy 6) Pathogenic alterations in two of the three following genes: TP53, RB1, and PTEN as determined by tissue or plasma tumor DNA commercial or academic assays. 7) Predominantly lytic bone metastases on imaging, 8) Presence of neuroendocrine markers on histology (positive staining of chromogranin A or synaptophysin) or in serum (abnormal high serum levels for chromogranin A or GRP) at initial diagnosis or at progression. Plus any of the following in the absence of other causes: A. elevated serum LDH (>= IULN); B. malignant hypercalcemia; C. elevated serum CEA (>2x IULN).

  2. Available archival tumor tissue for pathologic review and correlative studies. Tumor tissue (localized or metastatic) does not need to be received but rather identified and available (slides and/or blocks) to be sent to Duke.
  3. Documented progressive metastatic CRPC as determined by the provider based on at least one of the following criteria:

    1. PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2.0 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 2.0 ng/mL. Note: If confirmed rise is the only indication of progression, a minimal starting value of 1.0 ng/mL is acceptable, unless pure small-cell carcinoma.
    2. Soft-tissue progression based on new lesions or growth of existing soft tissue metastases.
    3. Progression of bone metastasis with one or more new bone lesion(s) by imaging.
  4. Castrate levels of serum total testosterone (<50 ng/dl) OR ongoing documented ADT unless pure small cell prostate cancer is present.
  5. Karnofsky performance status of 70 or higher.
  6. Acceptable initial laboratory values within 14 days of Cycle 1 Day 1
  7. Age >18
  8. Subjects with a partner who is a woman of child-bearing potential must agree to use one form of highly effective contraception as detailed in Section 8.3 of this protocol during the treatment period with cabazitaxel and for 3 months after the last dose of cabazitaxel and during the treatment period with nivolumab and for 7 months after the last dose of nivolumab, whichever is later. Subjects receiving cabazitaxel or nivolumab must also refrain from donating sperm during this period.
  9. Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information.
  10. Life expectancy of over 3 months as determined by treating physician.

Exclusion Criteria:

  1. Prior use of abiraterone or androgen receptor antagonists (ie enzalutamide) used to treat prostate cancer are permitted but should be stopped two or more weeks prior to study treatment initiation.
  2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
  3. Has received other prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study treatment initiation
  4. Prior receipt of cabazitaxel chemotherapy or 2 or more chemotherapy regimens. One prior chemotherapy regimen including docetaxel or platinum-containing chemotherapy is permitted.
  5. Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  6. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
  7. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
  8. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
  9. Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
  10. Has known active untreated CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment greater than prednisone 10mg (or equivalent) for at least 14 days prior to first dose of study intervention.
  11. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
  12. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  13. Has an active infection requiring systemic therapy.
  14. Has a known uncontrolled Human Immunodeficiency Virus (HIV) infection based on detectable HIV viral load and abnormal CD4 count of <350/mm3.
  15. Has a known active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
  16. Has a known active TB (Bacillus Tuberculosis) infection.
  17. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  18. Has known current psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  19. Has had an allogenic tissue/solid organ transplant.

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): NCT04709276


Contacts
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Contact: Julia Hurrelbrink, RN, BSN 919-681-1030 julia.hurrelbrink@duke.edu

Locations
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United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Julia Hurrelbrink, RN, BSN    919-681-1030    julia.hurrelbrink@duke.edu   
Principal Investigator: Andrew Armstrong, MD, ScM         
Sponsors and Collaborators
Andrew J. Armstrong, MD
Bristol-Myers Squibb
Investigators
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Principal Investigator: Andrew Armstrong, MD, ScM Duke University
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Responsible Party: Andrew J. Armstrong, MD, Professor of Medicine, Duke University
ClinicalTrials.gov Identifier: NCT04709276    
Other Study ID Numbers: Pro00106278
CA209-63X ( Other Identifier: Bristol Myers Squibb )
First Posted: January 14, 2021    Key Record Dates
Last Update Posted: June 10, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Andrew J. Armstrong, MD, Duke University:
Neuroendocrine Prostate Cancer
Aggressive Variant Prostate Cancer
Chemoimmunotherapy
Nivolumab
Ipilimumab
Carboplatin
Cabazitaxel
Additional relevant MeSH terms:
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Prostatic Neoplasms
Carcinoma, Neuroendocrine
Aggression
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Behavioral Symptoms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Carboplatin
Nivolumab
Ipilimumab
Antineoplastic Agents
Antineoplastic Agents, Immunological