Denosumab and Pembrolizumab in Clear Cell Renal Carcinoma

NCT03280667 | Unknown Phase 2 DMC

• 3 other identifiers: ANZUP16012014917153963
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 16

Brief Summary

This Single-arm, multicentre, phase 2 trial aims determine the activity and safety of pembrolizumab and denosumab in advanced clear cell renal cell carcinoma (ccRCC).

Conditions

Renal Cell Carcinoma, Clear Cell; Metastatic Kidney Cancer

Outcome Measures

Primary Outcomes (1)

• Objective tumour response

  The objective tumour response rate, as assessed by RECIST1.1 - This is defined as the proportion of participants in the analysis set with a confirmed complete response (CR) or partial response (PR) divided by the number of participants in the analysis set.

  Through study completion, on average 3.5 years

Secondary Outcomes (6)

• Progression-free survival (PFS)

  6 months

• Disease control rate (DCR)

  6 months

• Time to objective tumour response (OTR)

  Through study completion, on average 3.5 years

• Time to first skeletal related event (SRE)

  Through study completion, on average 3.5 years

• Frequency and severity of adverse events

  From time of patient registration, until 100 days after the last dose of treatment

Other Outcomes (1)

• Identification of tumour markers to predict outcomes

  Through study completion, on average 3.5 years

Study Arms (1)

Pembrolizumab plus Denosumab

EXPERIMENTAL

Pembrolizumab 200 mg IV every 3 weeks plus denosumab 120 mg SC on day 1, 8, 22 and then every 3 weeks with daily oral calcium and vitamin D, continued until disease progression or prohibitive toxicity

Drug: Pembrolizumab plus denosumab

Interventions

Pembrolizumab plus denosumab DRUG

Pembrolizumab 200 mg IV every 3 weeks plus denosumab 120 mg SC on day 1, 8, 22 and then every 3 weeks with daily oral calcium and vitamin D

Also known as: Keytruda and Xgeva

Pembrolizumab plus Denosumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults, aged 18 years and older, with histologically confirmed unresectable or metastatic renal cell carcinoma with a clear cell component
• Disease progression during or after VEGFR TKI treatment
• At least 1 target lesion according to RECIST v1.1
• ECOG performance status of 0-2
• Adequate bone marrow function (done within 14 days prior to registration
• Haemoglobin ≥ 90g/L
• Platelet ≥ 75x109/L
• Neutrophil count ≥ 1.5x109/L
• Adequate liver function (done within 14 days prior to registration and with values within the ranges specified below):
• Bilirubin ≤ 1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome
• AST or ALT ≤ 3.0 x ULN (or ≤ 5.0x ULN in the presence of liver metastases)
• Adequate renal function (done within 14 days prior to registration and with values within the ranges specified below):
• Creatinine ≤ 1.5x ULN OR
• Creatinine clearance (CrCl) ≥ 30mL/min
• Serum calcium or albumin-adjusted serum calcium ≥2.0 mmol/L

You may not qualify if:

• Prior treatment with pembrolizumab, or with any other anti-PD-1, anti-PD-L1, Anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways
• 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Any condition requiring systemic treatment with either corticosteroids (\>10mg daily prednisone or equivalent dose of alternative corticosteroid) or other immunosuppressive medications within 14 days of pembrolizumab administration. Intranasal, inhaled or topical steroids are permitted in the absence of active autoimmune disease.
• Prior treatment with denosumab.
• Untreated brain or leptomeningeal metastases or current clinical or radiological progression of known brain metastases, or requirement for steroid therapy for brain metastases. Patients with treated brain metastases are eligible if they have been stable and off steroids for ≥ 3 weeks.
• Prior allogeneic organ transplant, inflammatory bowel disease, pneumonitis, tuberculosis, or primary immunodeficiency
• Active infection requiring systemic therapy within 14 days before the first dose of pembrolizumab
• Receipt of live attenuated vaccination within 30 days of the planned first dose of pembrolizumab
• Active dental or jaw condition that precludes administration of denosumab:
• i) Significant dental/oral disease, including prior history or current evidence of osteonecrosis/osteomyelitis of the jaw, or; ii) Active dental or jaw condition which requires oral surgery, or; iii) Non-healed dental/oral surgery, or; iv) Planned invasive dental procedures during the course of the study
• Clinically significant hypersensitivity to denosumab or any components of denosumab
• Targeted small molecule therapy, surgery or radiation therapy within 2 weeks before registration, or persisting adverse event(s) of Grade 2 or more due to a previously administered agent. Note that participants who have had recent major surgery must have recovered adequately before registration.
• Life expectancy of less than 3 months.
• History of an active malignancy within the previous 5 years, except for locally curable cancers that have been apparently cured, such as low-grade thyroid carcinoma, prostate cancer not requiring treatment (Gleason grade ≤ 6), basal or squamous cell skin cancer, superficial bladder cancer, melanoma in situ, or carcinoma in situ of the prostate, cervix, or breast. Patients who have been free of other malignancies for ≥ 5 years prior to registration are eligible for this study.
• Significant infection, including chronic active hepatitis B, hepatitis C, or HIV. - Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol

Sponsors & Collaborators

• Australian and New Zealand Urogenital and Prostate Cancer Trials Group: lead
• Merck Sharp & Dohme LLC: collaborator
• Amgen: collaborator

Study Sites (16)

Border Medical Oncology Research Unit

Albury, New South Wales, 2640, Australia

Location

Northern Cancer Institute

Frenchs Forest, New South Wales, 2086, Australia

Location

Calvary Mater Newcastle

Newcastle, New South Wales, 2298, Australia

Location

St Vincent's Hospital Sydney

Sydney, New South Wales, 2010, Australia

Location

St George

Sydney, New South Wales, 2229, Australia

Location

Concord Repatriation General Hospital

Sydney, New South Wales, Australia

Location

Sunshine Coast University Hospital

Birtinya, Queensland, 4575, Australia

Location

Icon Cancer Care

Brisbane, Queensland, Australia

Location

Royal Brisbane and Womens hospital

Herston, Queensland, 4029, Australia

Location

Townsville Hospital

Townsville, Queensland, 4814, Australia

Location

Flinders Medical Centre

Adelaide, South Australia, Australia

Location

Box Hill

Box Hill, Victoria, 3128, Australia

Location

Monash Health

Melbourne, Victoria, Australia

Location

Peter MacCallum Cancer Center

Melbourne, Victoria, Australia

Location

Ballarat Oncology & Haematology Services

Wendouree, Victoria, Australia

Location

Fiona Stanley Hospital

Perth, Western Australia, 6150, Australia

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

pembrolizumab; Denosumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-arm, multicentre, phase 2 trial

Study Record Dates

• First Submitted: September 7, 2017
• First Posted: September 12, 2017
• Study Start: December 12, 2017
• Primary Completion: June 4, 2023
• Study Completion: June 4, 2023
• Last Updated: March 29, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Within 12 months of study completion
• Access Criteria: Authorised personnel as defined in the study contracts

Locations

AU (16)