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A Phase II, Multi-Centre, Study of the Efficacy and Safety of Sunitinib Given on an Individualized Schedule as First-Line Therapy for Metastatic Renal Cell Cancer


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Clear Cell, Metastatic Renal Cell Carcinoma

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Trial Information

A Phase II, Multi-Centre, Study of the Efficacy and Safety of Sunitinib Given on an Individualized Schedule as First-Line Therapy for Metastatic Renal Cell Cancer


This is a single-arm, single-stage phase II study investigating the use of an individualized
dosing regimen of Sunitinib on patients with metastatic renal cell carcinoma. The intent is
to maximize dose intensity of sunitinib and minimize time off therapy based on individual
tolerability using protocol directed dose modification criteria. Dose and schedule changes
are done if toxicity (hematological, fatigue, skin, GI) is > grade 2. There will be no
dosing or schedule changes for hypertension, hypothyroidism, skin color changes, heartburn,
etc. unless clinically indicated. Subjects will continue therapy until progression
according to RECIST 1.1 criteria. All subjects will be followed for progression free
survival until progression but after 2 years on therapy, only grade 3/4 drug related adverse
events will be recorded.

Fact-G and FKSI-DRS will be used to evaluate PRO/QOL at baseline and every 2 months
timepoints. Pharmacokinetic blood sampling will be collected on cycle 1, day 14 and again
on day 14 when a stable sunitinib schedule has been established for each subject. Biomarker
and genomics blood sampling for correlation with progression free survival, toxicity and
pharmacokinetics will be collected at baseline and stored.


Inclusion Criteria:



- 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.

Exclusion Criteria:

- 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

- Pregnancy or breastfeeding. Female subjects must be surgically sterile or be
postmenopausal, or must agree to use effective contraception during the period of
therapy. All female subjects with reproductive potential must have a negative
pregnancy test (serum) prior to enrolment. Male subjects must be surgically sterile
or must agree to use effective contraception during the period of therapy. The
definition of effective contraception will be based on the judgment of the principal
investigator or a designated associate

- Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, or may interfere with the interpretation of study results, and
in the judgment of the investigator would make the subject inappropriate for entry
into this study

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

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.

Outcome Time Frame:

3.5 years

Safety Issue:

No

Principal Investigator

Georg A. Bjarnason, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sunnybrook Health Sciences Centre

Authority:

Canada: Health Canada

Study ID:

OZM-042

NCT ID:

NCT01499121

Start Date:

May 2012

Completion Date:

December 2015

Related Keywords:

  • Clear Cell, Metastatic Renal Cell Carcinoma
  • Carcinoma
  • Carcinoma, Renal Cell

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