Neoadjuvant MEDI 4736 +/- Tremelimumab in Locally Advanced Renal Cell Carcinoma

NCT02762006 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CASE12815
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to investigate the safety and feasibility of administering investigational drugs (meaning not Food and Drug Administration (FDA)-approved for kidney cancer) prior to surgical treatment for kidney cancer. The first drug is called MEDI4736, and the second drug is called tremelimumab. Both of these drugs work by attaching to certain proteins on immune cells with the goal of stimulating an immune response against cancer cells. This is a phase 1 trial, with the primary goal of identifying if this treatment is safe and possible side effects when given prior to surgery for kidney cancer.

Conditions

Renal Cell Carcinoma; Kidney Cancer

Keywords

durvalumab; tremelimumab; Phase Ib; Locally Advanced

Outcome Measures

Primary Outcomes (1)

• Patients with Dose Limiting Toxicity (DTL)

  Dose-limiting toxicities (DLTs) will be evaluated from the first dose of drug through the first adjuvant dose of durvalumab. Grading of DLTs will follow the guidelines provided in the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

  Up to 12 months after screening

Secondary Outcomes (10)

• Average estimated blood loss during nephrectomy

  Up to 56 days after screening

• Average operative time (hours)

  Up to 56 days after screening

• Average length of hospital stay (days)

  Up to 56 days after screening

• Average days in the intensive care unit (ICU)

  Up to 56 days after screening

• Average volume of post operative blood transfusion

  Up to 56 days after screening

Study Arms (1)

Durvalumab + Tremelimumab with Nephrectomy

EXPERIMENTAL

Following systemic therapy, patients will undergo nephrectomy. Adjuvant therapy will be administered within 4-6 weeks of surgery. Subsequent follow-up will then be completed to assess adverse event resolution and long-term outcomes. * Cohort 1: Durvalumab x 1 dose (n=6) * Cohort 2: Durvalumab + Tremelimumab x 1 dose (n=6) * Cohort 2a: Durvalumab + Tremelimumab x 1 dose (n=12) * Cohort 3: Durvalumab + Tremelimumab x 1 dose (n=9) Cohorts 1 and 2: Adjuvant dosing of Durvalumab x 1 beginning 2-8 weeks after surgery. Cohort 2a: Durvalumab monotherapy until 1 year after nephrectomy. Cohort 3: Adjuvant dosing of durvalumab + tremelimumab x 1 beginning 2-8 weeks after surgery, then durvalumab monotherapy until 1 year after nephrectomy.

Drug: Durvalumab; Drug: Tremelimumab

Interventions

Durvalumab DRUG

Durvalumab is a programmed cell death ligand-1 monoclonal antibody which has demonstrated anti-tumor efficacy renal cell carcinoma and other malignancies via activation of the immune system.

Also known as: MEDI4736

Durvalumab + Tremelimumab with Nephrectomy

Tremelimumab DRUG

Tremelimumab is a CTLA-4 monoclonal antibody.

Durvalumab + Tremelimumab with Nephrectomy

Eligibility Criteria

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

You may qualify if:

• Radiographic evidence of renal cell carcinoma (any histologic subtype) without evidence of distant metastatic disease
• Patients must have clinical stage T2b-4 and/or N1, M0 disease
• Written informed consent and any locally-required authorization (e.g., HIPAA)) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate normal organ and marrow function as defined below:
• Hemoglobin ≥ 8.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (≥ 1500 per mm3)
• Platelet count ≥ 100 x 109/L (≥100,000 per mm3)
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with the study sponsor.
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal
• Glomerular filtration rate \> 40ml/min/1.73m2 as estimated by the Cockcroft-Gault formula or creatinine clearance \>50ml/min as determined by 24-hour urine collection:
• Estimated creatinine clearance (Clcr) in mL/min by the Cockcroft-Gault (C-G): {\[140 - age ( years)\]× weight (kg)}/{72 × serum creatinine (mg / dL)} ×0.85 for female patients
• Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). Previous enrollment in the present study.
• Participation in another clinical study with an investigational product during the last 30 days.
• Prior systemic anti-cancer therapy of any kind for RCC, including but not limited to any approved agent or any previous treatment with a PD1 or PD-L1 inhibitor including durvalumab. No previous treatment with immunotherapy for any malignancy including cytokine, anti-tumor vaccine, T-cell activator, co-stimulator or immune checkpoint inhibitor.
• Evidence of metastatic renal cell carcinoma on imaging and/or biopsy. Involvement of regional lymph nodes is permitted.
• Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from an electrocardiogram (ECG) using Fridericia's Correction (QTcF).
• a. At Screening, a single ECG will be obtained on which QTcF must be \<470 ms. In case of clinically significant ECG abnormalities, including a QTcF value \>470 ms, 2 additional 12-lead ECGs should be obtained over a brief period (eg, 30 minutes) to confirm the finding.
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
• Active or prior documented autoimmune disease within the past 2 years.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
• History of primary immunodeficiency
• History of allogeneic organ transplant
• History of hypersensitivity to durvalumab or any excipient
• History of hypersensitivity to tremelimumab or any excipient
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension (defined as \>160/90 mmHg despite medical therapy), unstable angina pectoris (requiring nitrates), cardiac arrhythmia (NOT including controlled atrial fibrillation), active peptic ulcer disease or gastritis, active bleeding diathesis including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C (detectable RNA) or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
• Known history of previous clinical diagnosis of tuberculosis

Sponsors & Collaborators

• Moshe Ornstein: lead

Study Sites (2)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Cleveland Clinic, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

durvalumab; tremelimumab

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

Study Officials

• Moshe Ornstein, MD, MA

  Cleveland Clinic, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 2, 2016
• First Posted: May 4, 2016
• Study Start: December 20, 2016
• Primary Completion: November 6, 2020
• Study Completion: November 6, 2020
• Last Updated: March 18, 2024

Record last verified: 2024-03

Locations

US (2)