Sequential Therapy in Metastatic Renal Cell Carinoma

NCT01731158 | Completed Phase 2

• 2 other identifiers: C-II-0082011-005939-78
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 13

Brief Summary

Sequential therapy with BEvacizumab, RAd001 (everolimus) and Tyrosinekinase inhibitors (TKI) in metastatic renal cell carcinoma (mRCC)

Conditions

Metastatic Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• PFS rate of 2nd line treatment at 6 months after randomisation

  PFS rate

  6 months after randomisation

Secondary Outcomes (6)

• PFS for 2nd line treatment

  after completion of second-line treatment (expected median treatment 1st and 2nd line: 16 months)

• PFS for each treatment given

  after completion of each treatment line (expected median treatment duration 1st line: 11 months, 2nd line: 5 months, 3rd line: 6 months)

• Overall Survival

  after death of patient

• number and severity (CTCAE 4.0) adverse events

  continuously throughout trial

• changes in quality of life throughout the Trial using FKSI questionnaires

  continuously throughout trial (baseline, week 5, week 11, every 12 weeks, end of treatment for all treatment lines via FKSI-10 questionnaire)

Study Arms (2)

arm A

OTHER

sequential therapy with approved drugs Avastin in combination with Roferon-A (first-line), Afinitor (second-line) and a TKI (Sutent, Nexavar or Votrient) (third-line)

Drug: Avastin in combination with Roferon-A; Drug: Afinitor; Drug: TKI: Sutent, Nexavar or Votrient

arm B

OTHER

sequential therapy with approved drugs Avastin in combination with Roferon-A (first-line), a TKI (Sutent, Nexavar or Votrient) (second-line) and Afinitor (third-line)

Drug: Avastin in combination with Roferon-A; Drug: Afinitor; Drug: TKI: Sutent, Nexavar or Votrient

Interventions

Avastin in combination with Roferon-A DRUG

Also known as: Bevacizumab in combination with Interfereon-alfa

arm A; arm B

Afinitor DRUG

Also known as: Everolimus

arm A; arm B

TKI: Sutent, Nexavar or Votrient DRUG

TKI

Also known as: Sunitinib, Sorafenib or Pazopanib

arm A; arm B

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent
• Adult males and females: ≥ 18 years of age.
• Metastatic or locally advanced RCC, not amendable to surgery with curative intention.
• ECOG performance status 0-1.
• Patients with measurable disease (at least one uni-dimensionally measurable target lesion by CT-scan or MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) If prior palliative radiotherapy to metastatic lesions: ≥ 1 measurable lesion that has not been irradiated. Patients with bone lesions as the only measurable lesion are eligible, provided that lesions consist of soft tissue, which is assessed via CT or MRI.
• Prior radiotherapy and surgery are allowed if completed 4 weeks (for minor surgery 2 weeks) prior to start of treatment and patient recovered from toxic effects.
• Modified MSKCC risk (according to Heng): good or intermediate.
• White blood cell count (WBC) ≥ 4x10\*9/L with neutrophils ≥ 1.5 x 10\*9/L, platelet count ≥ 100x10\*9/L, hemoglobin ≥ 9 g/dL.
• Total bilirubin ≤ 2 x upper limit of normal.
• AST and ALT ≤ 2.5 x upper limit of normal, or ≤ 5 x upper limit of normal in case of liver metastases.
• Serum creatinine ≤ 2 x upper limit of normal or calculated creatinine clearance \>30 ml/min.
• International Normalized Ratio (INR) ≤1.5 except for patients on stable anticoagulant therapy. Activated partial thromboplastin time (aPTT) ≤1.5 times upper limit of normal (ULN) or greater than the lower limit of the therapeutic range. Note: The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose of anticoagulants for at least two weeks at the treatment start.
• Adequate cardiac function (left ventricular ejection fraction ≥50% as assessed by ECHO)

You may not qualify if:

• Known or suspected allergy or hypersensitivity reaction to any of the components of study treatments or their excipients.
• Pregnancy (absence to be confirmed by beta-hCG test) or lactation period.
• Men or women of child-bearing potential who are sexually active and unwilling to use a highly effective method of contraception (Pearl index \< 1%) during the trial. Oral contraceptives are acceptable if a barrier method is applied in conjunction.
• Clinically symptomatic brain or meningeal metastasis (known or suspected), unless completion of local therapy for at least 3 months with discontinuation of steroids prior to start of treatment.
• Cardiac arrhythmias requiring anti-arrhythmics (excluding beta blockers, digoxin or digitoxin).
• History of any of the following cardiac events within the past 6 months:
• myocardial infarction (including severe/unstable angina),
• coronary/peripheral artery bypass graft,
• congestive heart failure (CHF) (NYHA Class III, or IV),
• cerebrovascular accident,
• transient ischemic attack,
• pulmonary embolism, abdominal or tracheo-oesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess
• Hemorrhage ≥ grade 3 or clinically significant hemoptysis within the past 4 weeks
• Uncontrolled severe hypertension (failure of diastolic blood pressure to fall below 90 mm Hg despite the use of ≥ 3 anti-hypertensive drugs).
• History of relevant pulmonary hypertension or interstitial lung disease or severely impaired lung function.

Sponsors & Collaborators

• Central European Society for Anticancer Drug Research: lead

Study Sites (13)

Charité Berlin

Berlin, Germany

Location

University Hospital Bonn

Bonn, Germany

Location

University Hospital Dresden

Dresden, Germany

Location

University Hospital Düsseldorf

Düsseldorf, Germany

Location

Waldkrankenhaus St. Marien

Erlangen, Germany

Location

University Hospital Essen

Essen, Germany

Location

University Hospital Frankfurt

Frankfurt, Germany

Location

University Hospital Freiburg

Freiburg im Breisgau, Germany

Location

University Hospital Göttingen

Göttingen, Germany

Location

Oncological Practice Hannover

Hanover, Germany

Location

University Hospital Hannover

Hanover, Germany

Location

University Hospital Magdeburg

Magdeburg, Germany

Location

University Hospital Tübingen

Tübingen, Germany

Location

Related Publications (1)

• Nel I, Gauler TC, Bublitz K, Lazaridis L, Goergens A, Giebel B, Schuler M, Hoffmann AC. Circulating Tumor Cell Composition in Renal Cell Carcinoma. PLoS One. 2016 Apr 21;11(4):e0153018. doi: 10.1371/journal.pone.0153018. eCollection 2016.

  PMID: 27101285 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Bevacizumab; Interferon alpha-2; Everolimus; Sorafenib; pazopanib; Sunitinib

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Interferon-alpha; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Sirolimus; Macrolides; Lactones; Organic Chemicals; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Pyrroles; Azoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Viktor Grünwald, MD

  University Hospital Hannover, Germany

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: September 28, 2012
• First Posted: November 21, 2012
• Study Start: October 1, 2012
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: February 6, 2019

Record last verified: 2019-02

Locations

DE (13)