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Palbociclib and Sasanlimab for the Treatment of Advanced Clear Cell Renal Cell Carcinoma (ccRCC) or Papillary Renal Cell Carcinoma (pRCC)

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: NCT05665361
Recruitment Status : Not yet recruiting
First Posted : December 27, 2022
Last Update Posted : January 31, 2023
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

Kidney cancer is the 12th leading cause of cancer-related death in the United States. Some kidney tumors do not respond well to current treatments. Better treatments are needed.

Objective:

To test a pair of drugs (sasanlimab and palbociclib) in people with kidney cancers.

Eligibility:

People aged 18 years and older with kidney cancer; specifically, clear cell renal cell carcinoma (ccRCC) or papillary renal cell carcinoma (pRCC).

Design:

Participants will be screened. They will have a physical exam with blood tests. They will have an imaging scan and a test of their heart function. They may have a biopsy; that is, a sample of tissue will be cut from the tumor.

Participants will be treated in 28-day cycles for up to 2 years.

Palbociclib is a pill taken by mouth. Participants will take this drug once a day for 21 days during each 28-day treatment cycle. They will write down the dates and times they take these pills in a diary.

Sasanlimab is an injection under the skin. Participants will receive this injection on the first day of each treatment cycle.

Imaging scans and blood tests will be repeated throughout the treatment. Tumor biopsies may be repeated up to 3 times; these biopsies are optional.

Participants will have follow-up visits every month for 3 months after treatment ends. They will continue to have imaging scans every 3 months; these scans may be done close to home. The results can be sent to researchers.

Participants will remain in the study up to 6 years.


Condition or disease Intervention/treatment Phase
Advanced Clear Cell Renal Carcinoma (Ccrcc) Papillary Renal Cell Carcinoma (Prcc) Drug: Sasanlimab Drug: Palbocicilib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Palbociclib and Sasanlimab for the Treatment of Advanced Clear Cell Renal Cell Carcinoma (ccRCC) or Papillary Renal Cell Carcinoma (pRCC)
Estimated Study Start Date : February 5, 2023
Estimated Primary Completion Date : June 1, 2025
Estimated Study Completion Date : June 1, 2025


Arm Intervention/treatment
Experimental: 1/ Phase I
Sasanlimab and deescalating doses of palbociclib
Drug: Sasanlimab
Sasanlimab will be given (SC on day 1 of every cycle, starting on day 1 (+/- 5 days) of cycle 2).

Drug: Palbocicilib
Palbociclib will be given PO for 21 days of every 28-day cycle, starting on day 1 of cycle 1.

Experimental: 2/Phase II
Sasanlimab and palbociclib at the dose determined in Phase I (RP2D)
Drug: Sasanlimab
Sasanlimab will be given (SC on day 1 of every cycle, starting on day 1 (+/- 5 days) of cycle 2).

Drug: Palbocicilib
Palbociclib will be given PO for 21 days of every 28-day cycle, starting on day 1 of cycle 1.




Primary Outcome Measures :
  1. Phase I: To determine RP2D of palbociclib in combination with sasanlimab [ Time Frame: 28 days ]
    Number of DLTs within DLT period

  2. Phase II: Objective response rate (ORR) [ Time Frame: 6 years ]
    Responses (PR+CR) in participants based on imaging [CT scan of chest, abdomen, and pelvis (or MRI of abdomen and pelvis with CT chest without contrast when appropriate)] performed every 8 (+/-1) weeks for 32 weeks and every 12 (+/-1) weeks after that until the first of either disease progression or 6 years after enrollment


Secondary Outcome Measures :
  1. Disease Control Rate (DCR) defined as PR + CR+ SD in participants re-treated with the study drug combination by RECIST 1.1 [ Time Frame: 6 years ]
    DCR as assessed by imaging [CT scan of chest, abdomen, and pelvis (or MRI of abdomen and pelvis with CT chest without contrast when appropriate)] performed every 8 (+/-1) weeks for 32 weeks and every 12 (+/-1) weeks after that until the first of either disease progression or 6 years after enrollment

  2. progression-free survival (PFS) [ Time Frame: 6 years ]
    Progression free survival determined by imaging [CT scan of chest, abdomen, and pelvis (or MRI of abdomen and pelvis with CT chest without contrast when appropriate)] performed every 8 (+/-1) weeks for 32 weeks and every 12 (+/-1) weeks after that until the first of either disease progression or 6 years after enrollment

  3. safety of the combination of palbociclib and sasanlimab [ Time Frame: 6 years ]
    Any toxicities identified between Day 1 of Cycle 1 through 90 days after the study agent (s) was/were last administered will be collected and reported by type and grade. Beyond 90 days after the last intervention, only adverse events which are serious and related to the study intervention will be recorded and reported. Note: during re-treatment AEs will be documented from the re-start of the study intervention through 90 days after the study agent (s) was/were last administered. Beyond 90 days after the last intervention, only adverse events which are serious and related to the study intervention need to be recorded

  4. overall survival (OS) [ Time Frame: 6 years ]
    Participants assessed at Day 1 of every cycle, safety follow up visits at days 30, 60, 90, every 12 weeks until progression and/or every 6 months after progression for 6 years after enrollment.



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:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Cytologically or histologically confirmed clear cell renal cell carcinoma (ccRCC) (Cohort 1) or papillary renal cell carcinoma (pRCC) (Cohort 2)
  • Participants must have advanced RCC with at least one measurable lesion as outlined in RECIST 1.1.
  • Participants with ccRCC (Cohort 1) must have received checkpoint inhibitor therapy and must have received or been ineligible to receive a VEGF pathway antagonist (as a single agent or as part of a combination)
  • Participants with pRCC (Cohort 2) can be treatment-na(SqrRoot) ve or have previously received systemic treatment for pRCC
  • Age >= 18 years
  • ECOG performance status <= 1
  • Adequate hematologic function at screening, as follows:

    • Absolute neutrophil count (ANC) >= 1,000/microliter
    • Hemoglobin (Hb) >= 9 g/dL with no blood transfusion within 2 weeks prior to treatment initiation
    • Platelets >= 100,000/microliter
  • Adequate renal and hepatic function at screening, as follows:

    • Serum creatinine <= 1.5 x upper limit of normal (ULN) OR, if >1.5x ULN, creatinine clearance (CrCl) >= 30 mL/min/1.73 m^2 (calculated CrCl (CKD-EPI or calculated eGFR provided by laboratory))
    • Total bilirubin <= 1.5 x ULN OR in participants with known or suspected Gilbert's syndrome, total bilirubin <= 3.0 x ULN
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 x ULN, (unless liver metastases are present, then values must be <= 5 x ULN)
  • Participants serologically positive for hepatitis C virus (HCV) are eligible if HCV viral load is undetectable
  • Participants serologically positive for human immunodeficiency virus (HIV) are eligible if they are on stable antiretroviral therapy for at least 4 weeks before treatment initiation, have no reported opportunistic infections or Castleman s disease within 12 months prior to treatment initiation, have a viral load that is undetectable by quantitative polymerase chain reaction (PCR) and CD4 count >= 200 cells per cubic millimeter
  • Participants with brain metastasis are eligible if at least 4 weeks status post radiotherapy or surgery before treatment initiation with no evidence of progression or associated symptoms
  • Women of child-bearing potential (WOCBP) and men must agree to use highly effective contraception (hormonal, intrauterine device (IUD), abstinence, tubal ligation, partner has had the previous vasectomy) starting at the time of study entry, for the duration of study therapy, and 6 months following the last dose of any study agent(s). NOTE: WOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal
  • Breastfeeding participants must be willing to discontinue breastfeeding from study enrollment through 6 months after study treatment discontinuation
  • Participants must be able to understand and be willing to sign a written informed consent document

EXCLUSION CRITERIA:

  • Prior treatment for RCC with chemotherapy, hormonal therapy, immunotherapy, treatment with an experimental agent, and/or radiation therapy within 4 weeks or 5 halflives, whichever is shorter, prior to treatment initiation
  • More than two prior lines of systemic therapy in the metastatic setting
  • Participants who have wound dehiscence from prior surgeries
  • Active inflammatory bowel disease, chronic diarrhea, gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of palbociclib
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agents
  • Prior history of grade >=3 immune-related adverse event(s) with checkpoint inhibitor therapy. Note: participants who had endocrine toxicity of grades 3 or 4 are eligible
  • An active autoimmune disease. Note: participants with type 1 diabetes, eczema, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease, adrenal insufficiency on systemic oral corticosteroid therapy (<= the equivalent of prednisone 10 mg/day) or other mild autoimmune disorders not requiring immunosuppressive treatment are eligible.
  • Participants receiving systemic corticosteroids at doses equivalent > 10 mg/daily of prednisone, cyclophosphamide, azathioprine, methotrexate, mycophenolate mofetil, sirolimus, thalidomide, or anti-tumor necrosis factor [anti-TNF] agents. Note: participants on steroids through a route known to result in minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are eligible
  • Prior allogeneic/autologous bone marrow or solid organ transplant
  • Participants with current or past hepatitis B (HBV) infection
  • Participants with a history of interstitial lung disease, non-infectious pneumonitis, or active/latent pulmonary tuberculosis (TB)
  • Participants taking medications that are strong inhibitors or inducers of CYP3A within 21 days or 5 half-lives of the agent (whichever is shorter) prior to initiation of study therapy
  • Participants taking any herbal supplements within 14 days prior to initiation of study therapy
  • History of a non RCC malignancy within 2 years of treatment initiation except for the following: adequately treated localized skin cancer, ductal carcinoma in situ, cervical carcinoma in situ, superficial bladder cancer, or other malignancy which does not require treatment at the current time per Standard of Care
  • Pregnant women (confirmed by <=-HCG serum pregnancy test performed at screening)
  • Uncontrolled intercurrent illness that would limit compliance with study requirements

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): NCT05665361


Contacts
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Contact: Brooksley Augustine (240) 858-3197 brooke.augustine@nih.gov
Contact: Ramaprasad Srinivasan, M.D. (240) 760-6251 ramasrin@mail.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Ramaprasad Srinivasan, M.D. National Cancer Institute (NCI)
Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT05665361    
Other Study ID Numbers: 10000666
000666-C
First Posted: December 27, 2022    Key Record Dates
Last Update Posted: January 31, 2023
Last Verified: January 18, 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: .All large scale genomic sequencing data will be shared with subscribers to dbGaP. All collected IPD will be shared with other investigators after publication in accordance with the executed CRADA.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Data from this study may be requested by other researchers at the time of publication or shortly thereafter. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active
Access Criteria: Data from this study may be requested by contacting the PI. Genomic data are made available via dbGaP through requests to the data custodians.

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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 National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Kidney Cancer
Kidney Neoplasms
Clear Cell Renal Cell Carcinoma
Papillary Renal Cell Carcinoma
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Kidney Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases