Phase II Sequential Treatment Trial of Single Agent Nivolumab, Then Combination Ipilimumab + Nivolumab in Metastatic or Unresectable Non-Clear Cell Renal Cell Carcinoma (ANZUP1602)

NCT03177239 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: ANZUP 1602
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 19

Brief Summary

This study aims to evaluate the safety, tolerability and effectiveness of new treatments for kidney cancer called Nivolumab and Ipilimumab. The study is in two parts; in the first instance patients receive nivolumab alone. If this treatment is not effective patients may move onto the second part of the trial, where they receive nivolumab + ipilimumab. There is no placebo. The reason to offer one treatment alone, followed by two treatments together is that it is thought that the double treatment may have more side-effects, but also may be effective in people in whom the single first treatment (nivolumab alone) has not helped. Nivolumab and ipilimumab are experimental treatments. This means that they are not an approved treatment for non-clear cell kidney cancer in Australia. The purpose of this study is to test the effectiveness, safety, and tolerability of Nivolumab (also known as Opdivo or BMS-936558) and Ipilumumab (also known as MDX-010 or Yervoy). Nivolumab and ipilimumab are antibodies (a type of human protein) that are being tested to see if they will allow the body's immune system to work against tumour cells. The immune system is the body's defence against cancer, bacteria and viruses. The effectiveness of nivolumab and ipilimumab in cancer of the kidney will be assessed by measuring the size of patient tumours via CT scans. Nivolumab and ipilimumab have been used alone or in combination in many other cancers, and are licenced for use in other cancers like advanced melanoma and bladder cancer in Australia. They have not been tested in people with non-clear cell kidney cancer. About 85 participants with non-clear cell kidney cancer are expected to participate in this study, from Australia and New Zealand. This research study has been initiated by Dr. Craig Gedye, is being conducted in collaboration with the Centre for Biostatistics and Clinical Trials (BaCT) and sponsored in Australia by the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group Pty Ltd. Bristol Myers Squibb (BMS) is supplying the study drugs and grant funding for this research.

Conditions

Renal Cell Carcinoma; Papillary Renal Cell Carcinoma Type 1; Papillary Renal Cell Carcinoma Type 2; Chromophobe Renal Cell Carcinoma; Sarcomatoid Renal Cell Carcinoma; Xp11 Translocation Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 5 years.

Secondary Outcomes (7)

• Duration of objective tumour response, as assessed by RECIST1.1

  Through study completion, on average 5 years.

• Progression-free survival (PFS), as assessed by RECIST1.1

  Through study completion, on average 5 years.

• Immune-related tumour response rate, as assessed by irRECIST.

  Through study completion, on average 5 years.

• Immune-related disease control rate (irDCR6), as assessed by irRECIST.

  At 6 months during treatment.

• The number of patients alive at the end of the study, as assessed by date of death.

  Through study completion, on average 5 years.

Other Outcomes (1)

• The biomarkers of response and resistance to anti-cancer treatments, as assessed by gene expression arrays, cytokine arrays, multiplex immunohistochemistry and mass cytometry on tissue and blood samples.

  Through study completion, on average 5 years.

Study Arms (1)

Nivolumab and Ipilimumab

EXPERIMENTAL

Part 1: nivolumab 240mg IV q2w for a maximum of 12 months. Part 2; nivolumab 240mg IV q3w in addition to ipilimumab 1mg/kg q3w x 4 cycles Then nivolumab 240mg q2w for a maximum of 12 months.

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

Dosage Form: Nivolumab BMS-936558-01 Solution for Injection Potency: 100 mg (10 mg/mL) Primary Packaging: 10 mL vial Appearance: Clear to opalescent colourless to pale yellow liquid. May contain particles. Storage Condition: 2 to 8°C. Protect from light and freezing.

Also known as: Opdivo

Nivolumab and Ipilimumab

Ipilimumab DRUG

Dosage Form: Ipilimumab Solution for Injection Potency: 200 mg (5 mg/mL) Primary Packaging: 40 mL vial Appearance: Clear, colourless to pale yellow liquid. May contain particles. Storage Condition: 2 to 8°C. Protect from light and freezing.

Also known as: Yervoy

Nivolumab and Ipilimumab

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed unresectable, locally advanced (defined as disease not amenable to curative surgery or radiation therapy) or metastatic nccRCC (both treatment-naïve or those treated with a VEGFR TKI or another systemic medical therapy). Non-clear cell histology including:
• Papillary renal cell carcinoma (type 1)
• Papillary renal cell carcinoma (type 2)
• Other: including chromophobe renal cell carcinoma, pure sarcomatoid renal cell carcinoma, Xp11 translocation (TFE3+ IHC) carcinoma, other renal carcinoma NOS
• Be ≥18 years of age on the day of signing informed consent
• At least 1 target lesion according to RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Adequate bone marrow function (should be performed within 14 days prior to registration and with values within the ranges specified below):
• Haemoglobin ≥ 90g/L
• Platelets ≥ 100x109/L
• Neutrophil count ≥ 1.5x109/L
• Adequate liver function (should be performed 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 participants with known Gilbert's syndrome who can have total bilirubin \< 3.0 mg/dL
• AST or ALT ≤ 3.0 x ULN (or ≤ 5.0x ULN in the presence of liver metastases)
• Adequate renal function (should be performed within 14 days prior to registration and with values within the ranges specified below):

You may not qualify if:

• Urothelial or transitional cell carcinoma of the renal pelvis or ureter
• Predominant clear cell renal cell carcinoma. A minority of clear cell histology (\<50%) is acceptable, but there must be \>50% non-clear cell histology predominant.
• Participation in a study of an investigational agent within 30 days of registration.
• Prior treatment with nivolumab, ipilimumab, 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 (NB Participant is eligible for Part 2 of the study if they took nivolumab monotherapy in Part 1 of the study).
• 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 registration. Intranasal, inhaled or topical steroids are permitted in the absence of active autoimmune disease. Participants are permitted to enrol 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.
• Untreated brain or leptomeningeal metastases or current clinical or radiological progression of known brain metastases or requirement for steroid therapy for brain metastases. Participants 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 registration.
• Receipt of live attenuated vaccination within 30 days of registration.
• Life expectancy of less than 3 months.
• Prior systemic therapy, surgery or radiation therapy within 4 weeks before registration.
• Note: If the participant has undergone major surgery, they must have recovered adequately before registration. Prior treatments with radiation therapy in the adjuvant and/or metastatic setting is permitted provided that therapy and is completed at least 14 days prior to the first dose of study drug and all treatment related adverse events are \< Grade 1 at the time of registration.
• History of another 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. Participants who have been free of other malignancies for ≥ 5 years prior to registration are eligible for this study.
• Positive test for hepatitis B virus surface antigen (HBVsAg) or antibodies to hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.

Sponsors & Collaborators

• Australian and New Zealand Urogenital and Prostate Cancer Trials Group: lead
• Bristol-Myers Squibb: collaborator

Study Sites (19)

Border Medical Oncology

Albury, New South Wales, 2460, Australia

Location

Campbelltown Hospital

Campbelltown, New South Wales, 2560, Australia

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

St Vincents Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

Northern Cancer Institute

Frenchs Forest, New South Wales, 2086, Australia

Location

St. George Hospital

Kogarah, New South Wales, 2217, Australia

Location

Calvary Mater Newcastle

Newcastle, New South Wales, 2298, Australia

Location

Port Macquarie Base Hospital

Port Macquarie, New South Wales, 2444, Australia

Location

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Tamworth Hospital - North West Cancer Centre

Tamworth, New South Wales, 2340, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Sunshine Coast University Hospital

Birtinya, Queensland, 4575, Australia

Location

Royal Brisbane & Women's Hospital

Brisbane, Queensland, 4000, Australia

Location

Flinders Medical Centre

Adelaide, South Australia, 5000, Australia

Location

Ashford Cancer Centre

Adelaide, South Australia, 5037, Australia

Location

Ballarat Oncology & Haematology Services

Ballarat, Victoria, 3355, Australia

Location

Box Hill Hospital - Eastern Health

Box Hill, Victoria, 3128, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

Related Links

• Sponsor's website

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney 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

Study Record Dates

• First Submitted: June 4, 2017
• First Posted: June 6, 2017
• Study Start: October 19, 2017
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2022
• Last Updated: February 16, 2022

Record last verified: 2022-02

Locations

AU (19)