A Study to Evaluate the Effectiveness of 5-Azacitidine and Bevacizumab in Advanced Renal Cell Carcinoma

NCT00934440 | Terminated Phase 1 Results DMC

• 1 other identifier: 11570
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 2

Brief Summary

To identify the maximum tolerable dose and assess qualitative/quantitative toxicities in patients with advanced renal cell cancer treated with combination of 5-azacitidine and bevacizumab.

Conditions

Renal Cell Carcinoma

Keywords

kidney cancer; renal cell

Outcome Measures

Primary Outcomes (1)

• Toxicities by Dose Level

  Toxicities determined using Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0

  3 to 6 months

Secondary Outcomes (1)

• Time to Progression

  2 years

Study Arms (1)

Dose Escalation: 5-azacitidine

EXPERIMENTAL

A traditional 3+3 dose escalation trial was implemented. Successive cohorts of patients (3 participants/cohort) received bevacizumab at the standard dose of 10mg/kg in combination with escalating doses of 5-azacitidine. If no dose limiting toxicity (DLT) is seen, subsequent patients will be treated at the next dose level. If one DLT is seen, an additional three patients will be accrued at that dose level. If two or more DLTs are seen at one dose level, then the previous dose level will be chosen for phase IIA. If two DLT's are seen at dose level 1, the trial will end. The standard 5-azacitidine dose is 75mg/m2/day for 7 days. If no DLT is seen at dose level 3, then we will proceed with the phase IIA portion of the study.

Drug: Bevacizumab; Drug: Azacitidine

Interventions

Bevacizumab DRUG

* First treatment: 10 milligram per kilograms (MG/KG) intravenously (IV) on Day 1every two weeks over 90 minutes. * Second treatment: 10 MG/KG IV on Day 1 every two weeks over 60 minutes. * Third and subsequent treatments: 10 MG/KG IV on Day 1 every two weeks over 30 minutes (minimum of two cycles).

Also known as: Avastin

Dose Escalation: 5-azacitidine

Azacitidine DRUG

* Dose level 1: 35 mg/m2/day for 7 days. * Dose level 2: 55 mg/m2/day for 7 days. * Dose level 3: 75 mg/m2/day for 7 days. * mg/m2/day = dose based on height and weight

Also known as: Vidaza

Dose Escalation: 5-azacitidine

Eligibility Criteria

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

You may qualify if:

• Age \> 18 years old
• ECOG Performance Status 0, 1 or 2
• Adequate bone marrow, liver and renal function as assessed by the following:
• Hemoglobin \> 9.0 g/dl
• Absolute neutrophil count(ANC)\>1,500/mm3
• Platelet count \>100,000/mm3
• Total bilirubin \< 1.5 times ULN
• ALT and AST \< 2.5 times the ULN (\< 5 x ULN for patients with liver involvement)
• Creatinine \< 1.5 times ULN
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to start of treatment.
• Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for duration of study. Men should use adequate birth control for at least 3 months after the last administration of Bevacizumab.
• Ability to understand and willingness to sign written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
• Patients not on anticoagulation must have an INR \< 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of treatment and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
• Must have histologically or cytologically confirmed renal cell carcinoma which is metastatic (M1). Patients with unresectable primary tumors (but MO) are eligible.
• Must have measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension. Soft tissue disease that has been radiated in the 2 months prior to registration is not assessable as measurable disease. Soft tissue disease within a prior radiation field must have progressed to be considered assessable. X-rays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration. X-rays, scans or physical examinations for non-measurable disease must have been completed within 42 days prior to registration.

You may not qualify if:

• Cardiac disease: Congestive heart failure \> class II NYHA. Must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
• Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of brain to exclude brain metastasis.
• Patients who have received prior bevacizumab are eligible for phase I portion of study but ineligible for phase II study.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• Uncontrolled hypertension defined as systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management.
• Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
• Active clinically serious infection \> CTCAE Grade 2.
• Thrombosis or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months. Patients with tumor related IVC thrombosis are eligible.
• Serious non-healing wound, ulcer, or bone fracture.
• Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.

Sponsors & Collaborators

• University of Kansas Medical Center: lead
• Celgene: collaborator

Study Sites (2)

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Stormont-Vail Cotton O'Neil Cancer Center

Topeka, Kansas, 66606, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

Bevacizumab; Azacitidine

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Dr. Peter Van Velduizen
• Organization: University of Kansas Cancer Center

SWILLIAM@kumc.edu

(913) 945-5059

Study Officials

• Peter J Van Veldhuizen, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2009
• First Posted: July 8, 2009
• Study Start: June 1, 2009
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: June 14, 2017
• Results First Posted: June 14, 2017

Record last verified: 2017-05

Locations

US (2)