Axitinib With or Without Anti-OX40 Antibody PF-04518600 in Treating Patients With Metastatic Kidney Cancer

NCT03092856 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 4K-16-5NCI-2017-00223P30CA014089
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 10

Brief Summary

This randomized phase II trial studies how well axitinib with or without anti-OX40 antibody PF-04518600 work in treating patients with kidney cancer that has spread to other parts of the body. Biological therapies, such as anti-OX40 antibody PF-04518600, use substances made from living organisms that may may stimulate the immune system in different ways and stop tumor cells from growing. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving axitinib with or without anti-OX40 antibody PF-04518600 may work better in treating patients with kidney cancer.

Conditions

Clear Cell Renal Cell Carcinoma; Metastatic Renal Cell Cancer; Recurrent Renal Cell Carcinoma; Stage IV Renal Cell Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  The statistical comparison of PFS in the two treatment arms will be based on the stratified logrank test.

  Time from randomization until the earliest of documented disease progression (confirmed progression of disease) or death, assessed for up to 180 days

Secondary Outcomes (2)

• Incidence of unacceptable toxicity

  Up to the beginning of the third course (29 days)

• ORR defined as either complete response or partial response occurring any time during treatment and assessed by RECIST 1.1 and immune-related RECIST (irRECIST) criteria

  Up to 180 days

Study Arms (2)

Arm I (axitinib, anti-OX40 antibody PF-04518600)

EXPERIMENTAL

Patients receive axitinib PO BID on days 1-14 and anti-OX40 antibody PF-04518600 IV over 60 minutes on day 1 beginning with course 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Biological: Anti-OX40 Antibody PF-04518600; Drug: Axitinib; Other: Laboratory Biomarker Analysis

Arm II (axitinib, placebo)

ACTIVE COMPARATOR

Patients receive axitinib as in Arm I and placebo IV on day 1 beginning with course 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Drug: Axitinib; Other: Laboratory Biomarker Analysis; Other: Placebo

Interventions

Anti-OX40 Antibody PF-04518600 BIOLOGICAL

Given IV

Also known as: PF-04518600

Arm I (axitinib, anti-OX40 antibody PF-04518600)

Axitinib DRUG

Given PO

Also known as: AG-013736, AG013736, Inlyta

Arm I (axitinib, anti-OX40 antibody PF-04518600); Arm II (axitinib, placebo)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (axitinib, anti-OX40 antibody PF-04518600); Arm II (axitinib, placebo)

Placebo OTHER

Given IV

Also known as: placebo therapy, PLCB, sham therapy

Arm II (axitinib, placebo)

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide informed consent
• Histological confirmation of renal cell carcinoma (RCC) with a predominantly (\> 50%) clear cell component
• Metastatic RCC
• Must have had a nephrectomy (radical or partial) and must provide the cell block from the nephrectomy
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)1.1 criteria
• Must have progression of disease within 6 months of study enrollment after treatment with only one of the following:
• Two prior lines of therapy: a VEGF inhibitor (other than axitinib), followed by a single agent PD-1/PDL-1 antibody, or
• One prior line of therapy: combination of a VEGF inhibitor (other than axitinib) AND a PD1/PDL1 antibody, or
• Additional prior systemic treatments not allowed
• Must agree to a fresh core or excisional biopsy from a metastatic site within a 12-week window prior to enrollment; if such a biopsy is already available, cell blocks must be provided; (Note: fine needle aspiration \[FNA\] and bone metastases samples are not acceptable for submission); specimens from the nephrectomy and fresh biopsy must be received and assessed for adequacy of tissue by the Data Coordinating Center (DCC) (University of Southern California \[USC\]) prior to randomization
• Zubrod performance status of =\< 2
• Women of childbearing potential must use method(s) of contraception; the individual methods of contraception should be determined in consultation with the treating physician or investigator
• Women of childbearing potential must have a negative serum pregnancy test within 24 hours prior to the administration of the investigational product; female patients who are not of childbearing potential as defined below, are eligible to be included (ie, meet at least one of the following criteria):
• Have undergone a documented hysterectomy and/or bilateral oophorectomy
• Have medically confirmed ovarian failure; or

You may not qualify if:

• Patients with known symptomatic brain metastases requiring systemic corticosteroids; patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable; mild neurological deficit is allowed, if it does not interfere with the ability to judge the safety on the trial
• Prior treatment with an mTOR inhibitor (including, but not limited to, everolimus, temsirolimus, sirolimus, and ridaforolimus)
• Prior treatment with axitinib
• History of or active autoimmune disorders (including but not limited to: Crohn's disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, Grave's disease) and other conditions that compromise or impair the immune system
• Active bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) -related illness
• Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose of study drug; inhaled steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease
• Uncontrolled adrenal insufficiency
• Any known active chronic liver disease
• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast
• Known medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results
• Prior treatment with an anti-CD137, or OX40 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways except anti-PD1, anti-PDL1/2 antibodies or ipilimumab
• Major surgery less than 6 weeks prior to the first dose of study drug; minor surgery less than 4 weeks prior to the first dose of study drug
• Anti-cancer therapy less than 6 weeks prior to the first dose of study drug (less than 28 days for bevacizumab) or palliative, focal radiation therapy less than 14 days prior to the first dose of study drug
• Presence of toxicities attributed to prior therapy other than alopecia that have not resolved to grade 1 (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version 4) or baseline before administration of study drug
• History of grade 3 or higher immune-mediated adverse event (including AST/ALT elevations that where considered drug related and cytokine release syndrome) that was considered related to prior immune-modulatory therapy (e.g., checkpoint inhibitors, costimulatory agents etc.) or any grade immune-related adverse events (AEs) that required immune suppressive therapy

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

Study Sites (10)

Los Angeles County-USC Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

USC Norris Oncology/Hematology-Newport Beach

Newport Beach, California, 92663, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

Weill Cornell Medical College, New York- Presbyterian Hospital

New York, New York, 10065, United States

Location

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22903, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Axitinib

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)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Sarmad Sadeghi

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2017
• First Posted: March 28, 2017
• Study Start: July 19, 2017
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 17, 2025

Record last verified: 2025-12

Locations

US (10)