A Study of Varlilumab (Anti-CD27) and Sunitinib in Patients With Metastatic Clear Cell Renal Cell Carcinoma

• ClinicalTrials.gov Identifier: NCT02386111
• Recruitment Status: Terminated
• First Posted: March 11, 2015
• Last Update Posted: July 25, 2018
• Sponsor: Celldex Therapeutics
• Information provided by (Responsible Party): Celldex Therapeutics

Study Description

Brief Summary:

This is a study to determine the clinical benefit (how well the drug works), safety, and tolerability of combining varlilumab and sunitinib. The study will enroll patients with metastatic clear cell renal cell carcinoma.

Condition or disease	Intervention/treatment	Phase
Carcinoma, Renal Cell; Kidney Diseases; Kidney Neoplasms; Urogenital Neoplasms; Urologic Diseases; Urologic Neoplasms; Neoplasms; Neoplasms by Histologic Type; Clear-cell Metastatic Renal Cell Carcinoma	Drug: Combination of varlilumab and sunitinib	Phase 1

Detailed Description:

Varlilumab is a fully human monoclonal antibody that binds to a molecule called CD27 found on certain immune cells and may act to promote anti-tumor effects.

Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs) some of which play a role in tumor growth and progression of cancer.

This study will evaluate the safety, tolerability and efficacy of the anti-CD27 antibody varlilumab in combination with sunitinib.

Eligible patients that enroll in the dose escalation portion of the study will be assigned to one of three dose levels of varlilumab in combination with 50 mg of sunitinib. The first phase of the study will test the safety profile of the combination and determine which dose of varlilumab will be studied in Phase ll* of the overall study.

*Note: This Study was terminated prior to initiation of Phase II.

All patients enrolled in the study will be closely monitored to determine if there is a response to the treatment as well as for any side effects that may occur.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 17 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase l/ll Study of Varlilumab in Combination With Sunitinib in Patients With Metastatic Clear Cell Renal Cell Carcinoma
• Study Start Date: May 2015
• Actual Primary Completion Date: August 2017
• Actual Study Completion Date: November 3, 2017

Arms and Interventions

Arm

Intervention/treatment

Experimental: Varlilumab and Sunitinib

Drug: Combination of varlilumab and sunitinib; During the treatment phase of the study, eligible patients will receive varlilumab for up to 8 cycles. Treatment cycles are 6 weeks each with varlilumab administered once every 3 weeks and sunitinib administered daily for 4 weeks followed by a 2 week rest. There is no limit on the number of cycles of sunitinib. Patients may be discontinued from receiving study treatment (sunitinib or varlilumab) based on the results of disease assessments or if experiencing side effects that make study therapy intolerable. Phase l Dose: The planned dose of varlilumab will be dependent on the cohort assigned at enrollment. Varlilumab doses are 0.3 mg/kg, 1 mg/kg or 3 mg/kg. The Study was terminated prior to initiation of Phase II. All patients will receive sunitinib at a dose of 50 mg.

Outcome Measures

Primary Outcome Measures :

1. Phase 1: Safety and tolerability of varlilumab and varlilumab in combination with sunitinib as measured by incidence of drug related adverse events (AEs), serious drug related AEs, dose-limiting toxicities and laboratory test abnormalities. [ Time Frame: Safety follow-up is 100 days from last study drug dose. ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Histologically confirmed diagnosis of predominant clear cell renal cell carcinoma.
2. Advanced metastatic disease
3. Documented progressive disease based on radiographic, clinical or pathologic assessment during or subsequent to last therapy.
4. For Phase l, no more than 3 prior anticancer regimens (IL-2 or interferon do not count towards the total).
5. Measurable (target) disease.
6. Life expectancy ≥ 12 weeks.
7. If of childbearing potential (male or female), agrees to practice an effective form of contraception during study treatment and for at least 70 days following last treatment dose.
8. Must have available tumor tissue and consent to biopsy while on study.

Exclusion Criteria:

1. Prior therapy with an anti-CD27 antibody.
2. Previous treatment with sunitinib.
3. Use of any experimental immunotherapy.
4. Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to the planned start of study treatment.
5. Systemic radiation therapy within 4 weeks, prior focal radiotherapy within 2 weeks, or radiopharmaceuticals (strontium, samarium) within 8 weeks prior to the first dose of study treatment.
6. Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to first dose of study treatment.
7. Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancers; or any other cancer from which the patient has been disease-free for at least 3 years.
8. Active, untreated central nervous system metastases.
9. Active autoimmune disease or a documented history of autoimmune disease.
10. Active diverticulitis.
11. Significant cardiovascular disease including CHF or poorly controlled hypertension.
12. Impairment of gastrointestinal function or gastrointestinal disease that may alter the absorption of sunitinib.

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

United States, California

UC Davis Comprehensive Cancer Center

Sacramento, California, United States, 95817

UCSF Helen Diller Comprehensive Cancer Center

San Francisco, California, United States, 94158

United States, District of Columbia

George Washington University-Medical Faculty Associates

Washington, District of Columbia, United States, 20037

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

United States, Nebraska

Nebraska Cancer Specialists

Omaha, Nebraska, United States, 68130

United States, New York

Mount Sinai Medical Center

New York, New York, United States, 10029

United States, Pennsylvania

Thomas Jefferson University

Philadelphia, Pennsylvania, United States, 19107

Sponsors and Collaborators

Celldex Therapeutics

More Information

• Responsible Party: Celldex Therapeutics
• ClinicalTrials.gov Identifier: NCT02386111 History of Changes
• Other Study ID Numbers: CDX1127-04
• First Posted: March 11, 2015
• Last Update Posted: July 25, 2018
• Last Verified: November 2017

Keywords provided by Celldex Therapeutics:

Sutent

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms; Neoplasms by Histologic Type; Urogenital Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Neoplasms; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Neoplasms by Site; Sunitinib; Antibodies, Monoclonal; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Immunologic Factors