Clinical trial NCT01361113: Neoadjuvant Pazopanib in Renal Cell Carcinoma
Official title: Neoadjuvant Pazopanib: A Phase II Study to Evaluate the Effect on Disease Response and Recurrence and to Establish Predictive Biomarkers of Drug Activity in Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Renal Cell Carcinoma
Keywords: Renal Cell Carcinoma
RCC
Votrient
Pazopanib
Nephrectomy
Neoadjuvant
Phase II
LCCC 1028
Lineberger Comprehensive Cancer Center
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2011-05-26
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will be a single arm phase II clinical trial of 8 weeks of daily, oral neo-adjuvant pazopanib prior to nephrectomy in 39 evaluable patients with histologically confirmed localized renal cell carcinoma (RCC).

Detailed description: The primary objective of this study is to determine the objective response rate Complete Response + Partial Response(CR+PR) associated with neoadjuvant pazopanib at 8 weeks as defined via Response Evaluation Criteria in Solid Tumors (RECIST1.1). The investigators will also estimate the recurrence free survival (RFS), specifically the 1 and 2 year rates, with recurrence defined via RECIST1.1, and characterize the safety issues. Finally, this study also includes a number of exploratory analyses designed to evaluate potential correlations between RFS and; serum levels of cytokine and angiogenesis factor (CAF).

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years with radiographic evidence of nonmetastatic renal cell carcinoma
* Histological verification of clear cell renal cell carcinoma (-Clinical stage 2 (7 cm) or greater with localized disease
* No evidence of extranodal metastatic disease
* Appropriate candidate for surgery
* The Eastern Cooperative Oncology Group (ECOG) Performance status of 0-1
* Adequate organ function
* Serum calcium, magnesium, potassium within normal limits, or if outside of normal limits, must be deemed clinically insignificant by the Investigator.
* No known coagulopathy
* Ability to read and follow instructions
* Women of childbearing potential must have a negative serum pregnancy test performed within 14 days prior to the start of pazopanib treatment and both men and women must be willing to use adequate contraception.
* Able to provide written, informed consent
* Blood and urine samples must be provided from all subjects for biomarker analysis before and during treatment with pazopanib

Exclusion Criteria

* Known or suspected allergy to pazopanib
* Inability to swallow or retain oral medication
* Prior malignancy Exception: Subjects who have had another malignancy and have been disease-free for three years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
* Unable or unwilling to discontinue use of prohibited medications at least 7 days prior to the first dose of study drug and for the duration of the study.
* Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including
* History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
* History of any one or more cardiovascular conditions within the past 6 months
* Hypertension \[defined as systolic blood pressure (SBP) of ≥140 mmHg OR diastolic blood pressure (DBP) of ≥ 90 mmHg in spite of optimal medical management.
* Evidence of active bleeding or bleeding diathesis.
* Any serious and/or unstable pre-existing medical (especially hepatic disease), psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
* Prior major surgery or trauma within 28 days prior to first dose of pazopanib and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major).
* Pregnant or breastfeeding; breastfeeding may not resume for 14 days after the last dose of pazopanib
* Prior treatment with any of the following anti-cancer therapies for treatment of their RCC:

  * radiation therapy, surgery or tumor embolization
  * chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy
* Baseline Corrected QT Interval (QTc) \>480 msec or other clinically significant baseline ECG abnormality

Primary outcomes:
measure: Response Rate
timeFrame: 8 weeks after neoadjuvant treatment
Secondary outcomes:
measure: Recurrence Free Survival (RFS)
timeFrame: 2 years
measure: Number of Participants Who Needed an Altered Surgical Approach After Treatment With Pazopanib
timeFrame: 14 weeks
measure: Number of Participants With Adverse Events Related to Treatment.
timeFrame: 9 weeks
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: North Carolina Cancer Hospital (UNC)
state: North Carolina
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: William Kim, MD
role: PRINCIPAL_INVESTIGATOR
References: