Study of Interleukin-2, Interferon-alpha and Bevacizumab in Metastatic Kidney Cancer

NCT01274273 | Unknown Phase 2 DMC

• 1 other identifier: DARENCA-1
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine whether interleukin-2, interferon-alpha in combination with bevacizumab are effective in the treatment of metastatic renal cell carcinoma (mRCC).

Conditions

Metastatic Renal Cell Carcinoma

Keywords

Bevacizumab; interleukin-2; interferon-alpha

Outcome Measures

Primary Outcomes (1)

• Progression free survival, PFS

  This is defined as the time between date of randomisation and the first date of documented disease progression or date of death due to any cause.

Secondary Outcomes (10)

• Response rate, RR

  Overall response rate as assessed by the RECIST 1.1 criteria. An overall response is defined as a confirmed complete response (CR) or confirmed partial response (PR).

• Overall survival, (OS)

  Overall survival is defined as the time between date of randomisation and the date of death due to any cause.

• Duration of response

  Duration of response is defined as the time between the date a response (CR or PR) was first seen until date of progression.

• Time to progression, (TTP)

  Time to progression is defined as time between date of randomisation and date of documented progression.

• Time to treatment failure, (TTTF)

  see below

Study Arms (2)

Interleukin-2, interferon, bevacizumab

EXPERIMENTAL

Drug: Bevacizumab

Interleukin-2 and interferon-alfa

ACTIVE COMPARATOR

Drug: Interleukin-2; Drug: Interferon Alfa-2b

Interventions

Interleukin-2 DRUG

2.4 MIU/m2 s.c. two times daily, 5 days per week, weeks 1 and 2, every 28-day-cycle, for a maximum of 9 cycles (i.e.for a maximum of 9 months).

Also known as: Aldesleukin

Interleukin-2 and interferon-alfa

Interferon Alfa-2b DRUG

IFN-alfa given as one priming-week of daily IFN 3.0 MIU, followed by up to 9 treatment cycles (i.e. for a maximum of 9 months) with IFN-alfa 3.0 MIU as a fixed dose s.c. once daily - 5 days per week.

Also known as: IntronA

Interleukin-2 and interferon-alfa

Bevacizumab DRUG

Bevacizumab doses of 10 mg per kilogram of body weight, given every two weeks i.v. until disease progression, unacceptable toxicity, withdrawal of consent or a maximum of 1 year following obtaining no evidence of disease (NED).

Also known as: Avastin

Interleukin-2, interferon, bevacizumab

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent
• Patient must be willing and able to comply with the protocol.
• Age ≥ 18 years.
• Histologic og cytologic biopsy proven locally advanced or metastatic renal cell carcinoma, considered non-candidates for curative surgery. Nephrectomy is not mandatory.
• Patient with renal cell carcinoma (RCC) with a clear-cell histologic component confirmed by local pathology review.
• Females with a negative serum pregnancy test unless childbearing potential can be otherwise excluded
• Fertile women of childbearing potential (\<2 years after last menstruation) and men must use effective means of contraception
• Memorial-Sloan-Kettering-Cancer-Centre favourable- and intermediate prognostic group.
• Measurable or non-measurable disease (as per RECIST1.1 criteria)
• Karnofsky Performance status of 70% or higher.
• Life expectancy greater than 4 months.
• The required laboratory values at baseline are as follows:
• Haematology:
• WCC ≥ 3.0 x 109/L, Platelet count ≥ 100 x 109/L, Haemoglobin ≥ 6.2 mmol/l, (INR) ≤ 1.5, APTT ≤ 1.5 x ULN
• Biochemistry:

You may not qualify if:

• Prior systemic treatment for metastatic RCC disease
• Major surgical procedure, open surgical biopsy, or significant traumatic injury within 28 days prior to randomization.
• Serious non-healing wound, ulcer or bone fracture.
• Evidence of current central nervous system (CNS) metastases or spinal cord compression. Patient must undergo an MRI or CT scan of the brain (with contrast, if possible) within 28 days prior to randomization.
• Seizure(s) not controlled with standard medical therapy.
• Dipstick urine test of protein ≥ 2+.
• Other malignancies within 5 years prior to randomization (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix).
• Evidence of bleeding diathesis or coagulopathy.
• Ongoing or recent (within 10 days prior to study treatment start) need for full therapeutic dose of oral anticoagulants or chronic daily treatment with aspirin. Low molecular weight heparin are allowed
• Uncontrolled hypertension (≥ 160 mm Hg systolic and/or ≥ 100 mm Hg diastolic) while receiving chronic medication.
• Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents (≤ 6 months before randomisation), myocardial infarction (≤ 6 months before randomisation), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication.
• Recent (within the 30 days prior to randomization) treatment with another investigational drug or participation in another investigational study.
• Chronic treatment with corticosteroids (dose of ≥ 10 mg/day methylprednisolone equivalent), excluding inhaled steroids.
• History or presence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or patient at high risk from treatment complications.
• Known hypersensitivity to interleukin-2, Interferon, alfa or bevacizumab.

Sponsors & Collaborators

• University of Aarhus: lead
• Danish Renal Cancer Study Group: collaborator

Study Sites (2)

Aarhus University Hospital

Aarhus, Aarhus, 8000, Denmark

Location

Herlev University Hospital

Herlev, Herlev, 2730, Denmark

Location

Related Publications (3)

• Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.

  PMID: 37146227 DERIVED

• Drljevic-Nielsen A, Rasmussen F, Nielsen PS, Stilling C, Thorup K, Mains JR, Madsen HHT, Donskov F. Prognostic value of DCE-CT-derived blood volume and flow compared to core biopsy microvessel density in patients with metastatic renal cell carcinoma. Eur Radiol Exp. 2021 Jul 30;5(1):32. doi: 10.1186/s41747-021-00232-2.

  PMID: 34327591 DERIVED

• Donskov F, Jensen NV, Smidt-Hansen T, Brondum L, Geertsen P. A randomized phase II trial of interleukin-2 and interferon-alpha plus bevacizumab versus interleukin-2 and interferon-alpha in metastatic renal-cell carcinoma (mRCC): results from the Danish Renal Cancer Group (DaRenCa) study-1. Acta Oncol. 2018 May;57(5):589-594. doi: 10.1080/0284186X.2018.1433324. Epub 2018 Feb 2.

  PMID: 29392960 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Interleukin-2; aldesleukin; Interferon alpha-2; Bevacizumab

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)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Interferon-alpha; Interferon Type I; Interferons; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Study Officials

• Frede Donskov, MD, DMSc

  Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

• Poul Geertsen, MD, PhD

  University of Copenhagen

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2010
• First Posted: January 11, 2011
• Study Start: October 1, 2009
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 2, 2014

Record last verified: 2012-08

Locations

DK (2)