Study of Efficacy and Safety of Sunitinib Given on an Individualized Schedule

NCT01499121 | Completed Phase 2 DMC

• 1 other identifier: OZM-042
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 13

Brief Summary

This prospective single arm study will evaluate the efficacy and safety of sunitinib given on an individualized dosing schedule as first-line therapy in subjects with metastatic clear cell renal cell cancer. The treatment schedule intent is to maximize dose intensity of sunitinib and minimize time off therapy based on individual tolerability using protocol directed dose modification criteria. A total of 110 subjects will be enrolled. All subjects will continue to receive study treatment until disease progression or withdrawal of consent. The primary outcome for this study is progression-free survival (PFS), defined as the duration from the date a patient first receives Sunitinib until the date of death or confirmed progression according to the RECIST criteria.

Conditions

Clear Cell, Metastatic Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression free survival for sunitinib given on an individualized dose/schedule

  Primary objective is to characterize the progression free survival for sunitinib given on an individualized dose/schedule in patients on first-line treatment for metastatic renal cell cancer. Subjects will continue therapy until progression according to RECIST criteria version 1.1. Tumour measurements using physical exam, spiral CT scan and/or MRI or other appropriate techniques deemed suitable by the investigator will be performed at screening and repeated at the end of every 2 cycles until disease progression.

  3.5 years

Secondary Outcomes (3)

• Patient tolerability and safety of an individualized dose/schedule

  3.5 years

• Dose intensity of sunitinib given on an individualized dose/schedule.

  3.5 years

• Overall survival and patient quality of life

  3.5 years

Study Arms (1)

Sunitinib

OTHER

Starting dose/schedule of Sunitinib 50 mg/28 days on, 14 days off. The intent is to maximize dose intensity of Sunitinib and minimize time off therapy based on individual tolerability using dose modification criteria.

Drug: Sunitinib

Interventions

Sunitinib DRUG

The starting dose will be 50 mg Sunitinib on the 28/14 schedule. In patients that develop ≥ grade-2 toxicity after 2 weeks, therapy will be held for 7 days or resolution before continuing therapy according to the 1st dose/schedule change. In patients that do not develop ≥ grade-2 toxicity, therapy will continue for 1-2 weeks or until ≥ grade-2 toxicity. In patients that develop \> grade-2 toxicity after less than 4 weeks, therapy will be held for 7 days or before continued according to the 1st dose/schedule change. Patients that do develop grade-2 toxicity (but no more) on the 50 mg 28/14 schedule, will remain on schedule but the time off therapy will be reduced to 7 days if toxicity has resolved after a 7-day break. Patients that develop ≤ grade-1 toxicity on the 50 mg 28/14 schedule, will be dose escalated according to protocol.

Also known as: Sutent, SU11248

Sunitinib

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed locally recurrent or metastatic renal cell carcinoma of clear cell origin or with a component of clear cell histology.
• Patients with nephrectomy (partial or total) or without nephrectomy are eligible.
• Evidence of measurable disease by RECIST criteria version 1.1.
• Male or female, age ≥ 18 years old
• Karnofsky performance status ≥ 80 %.
• Adequate organ functions determined by protocol directed lab values
• Subject's willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

You may not qualify if:

• Renal cell carcinoma without any clear (conventional) cell component.
• Prior systemic therapy of any kind for advanced RCC (including targeted therapy, immunotherapy, chemotherapy, hormonal, or investigational therapy). Prior neo-adjuvant or adjuvant therapy with cytokines, IL-2 or vaccines is only permitted if it did not occur within the preceding 12 months. Prior and/or concurrent bisphosphonate therapy is allowed.
• Major surgery or radiation therapy within 4 weeks of starting the study treatment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated
• NCI CTCAE Version 3.0 grade 3 haemorrhage within 4 weeks of starting the study treatment
• Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell carcinoma, squamous cell skin cancer, or in situ cervical cancer
• Known brain metastases, spinal cord compression, or evidence of symptomatic brain or leptomeningeal carcinomatosis on screening CT or MRI scan.
• Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism
• Ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade ≥2
• Prolonged QTc interval on baseline EKG (\>450 msec for males or \>470 msec for females).
• Atrial Fibrillation of any grade.
• Uncontrolled hypertension (\>150/100 mm Hg despite optimal medical therapy.
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection.
• Concurrent treatment on another clinical trial. Supportive care trials or non-treatment trials, e.g. QOL, and imaging trials are allowed.
• Concomitant treatment with a drug having proarrhythmic potential
• Use of potent CYP3A4 inhibitors and inducers 7 and 12 days before dosing, respectively

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Pfizer: collaborator

Study Sites (13)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BC Cancer Agency - Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 3A7, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

Kingston General Hospital Research Institute

Kingston, Ontario, K7L 2V7, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 4L6, Canada

Location

Durham Regional Cancer Centre

Oshawa, Ontario, L1G 2B9, Canada

Location

Ottawa Hospital Cancer Centre

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Notre-Dame Hospital

Montreal, Quebec, H2W 1T8, Canada

Location

Related Publications (1)

• Bjarnason GA, Knox JJ, Kollmannsberger CK, Soulieres D, Ernst DS, Zalewski P, Canil CM, Winquist E, Hotte SJ, North SA, Heng DYC, Macfarlane RJ, Venner PM, Kapoor A, Hansen AR, Eigl BJ, Czaykowski P, Boyd B, Wang L, Basappa NS. The efficacy and safety of sunitinib given on an individualised schedule as first-line therapy for metastatic renal cell carcinoma: A phase 2 clinical trial. Eur J Cancer. 2019 Feb;108:69-77. doi: 10.1016/j.ejca.2018.12.006. Epub 2019 Jan 14.

  PMID: 30648632 DERIVED

MeSH Terms

Conditions

Clear-cell metastatic renal cell carcinoma

Interventions

Sunitinib

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Georg A. Bjarnason, MD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Oncologist

Study Record Dates

• First Submitted: December 12, 2011
• First Posted: December 26, 2011
• Study Start: May 1, 2012
• Primary Completion: September 30, 2017
• Study Completion: September 30, 2017
• Last Updated: March 6, 2018

Record last verified: 2018-03

Locations

CA (13)