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

Sponsor

Celldex Therapeutics (Industry)

Overall Status

Terminated

CT.gov ID

NCT02386111

Collaborator

(none)

Enrollment

Locations

Arm

30.1

Duration (Months)

1.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

Actual Enrollment :

17 participants

Allocation:

N/A

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 1, 2015

Actual Primary Completion Date :

Aug 1, 2017

Actual Study Completion Date :

Nov 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.

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

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. [Safety follow-up is 100 days from last study drug dose.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed diagnosis of predominant clear cell renal cell carcinoma.
Advanced metastatic disease
Documented progressive disease based on radiographic, clinical or pathologic assessment during or subsequent to last therapy.
For Phase l, no more than 3 prior anticancer regimens (IL-2 or interferon do not count towards the total).
Measurable (target) disease.
Life expectancy ≥ 12 weeks.
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.
Must have available tumor tissue and consent to biopsy while on study.

Exclusion Criteria:

Prior therapy with an anti-CD27 antibody.
Previous treatment with sunitinib.
Use of any experimental immunotherapy.
Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to the planned start of study treatment.
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.
Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to first dose of study treatment.
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.
Active, untreated central nervous system metastases.
Active autoimmune disease or a documented history of autoimmune disease.
Active diverticulitis.
Significant cardiovascular disease including CHF or poorly controlled hypertension.
Impairment of gastrointestinal function or gastrointestinal disease that may alter the absorption of sunitinib.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	UC Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
3	UCSF Helen Diller Comprehensive Cancer Center	San Francisco	California	United States	94158
4	George Washington University-Medical Faculty Associates	Washington	District of Columbia	United States	20037
5	University of Michigan	Ann Arbor	Michigan	United States	48109
6	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
7	Nebraska Cancer Specialists	Omaha	Nebraska	United States	68130
8	Mount Sinai Medical Center	New York	New York	United States	10029
9	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107