Pazopanib Versus Temsirolimus in Poor-Risk Clear-Cell Renal Cell Carcinoma (RCC)

NCT01392183 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2011-0358NCI-2011-01277
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to compare pazopanib to temsirolimus in the treatment of advanced clear-cell renal cell carcinoma. The safety of each drug will also be studied. Pazopanib is designed to block the growth of blood vessels that supply nutrients needed for tumor growth. This may prevent or slow the growth of cancer cells. Temsirolimus is designed to block the growth of cancer cells, which may cause cancer cells to die. This is an investigational study. Pazopanib and temsirolimus are both FDA approved and commercially available for the treatment of kidney cancer. It is investigational to compare the 2 drugs. Up to 90 patients will be enrolled in this study. All will be enrolled at MD Anderson.

Conditions

Kidney Cancer

Keywords

Kidney cancer; Renal Cell Carcinoma; Poor-Risk Clear-Cell Renal Cell Carcinoma; RCC; Metastatic; Locally advanced; Complete response; CR; Partial Response; PR; Overall survival; OS; Time to progression; TTP; Pazopanib; GW786034; Temsirolimus; CCI-779; Torisel; Benadryl; Diphenhydramine; TemPa

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS is measured from the initiation of treatment to the time of first disease progression or death due to any reason during the first drug administration in each arm. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 20% or more increase in the sum of the longest diameters of target lesions, or a measurable increase in a non-target lesion or the appearance of new lesions. The PFS median of first drug pazopanib (treatment group) was compared to the PFS median of first drug temsirolimus (control group) in an adjusted Hazard ratio. The hazard ratio compares events from a treatment group to a control group. If the hazard ratio is greater than 1the treatment group performed better. If the hazard ratio is less than 1 the control group performed better. If the hazard ratio is equal to 1, then the groups performed equally.

  Measured form start of treatment up to 3 years

Secondary Outcomes (1)

• Overall Survival (OS)

  From the start of treatment up to 6 years or death, whichever came first

Study Arms (2)

Pazopanib

EXPERIMENTAL

Pazopanib 800 mg by mouth daily. Quality of Life Assessment - Completion of full assessment battery at baseline, prior to treatment then every 8 weeks at clinical evaluation.

Drug: Pazopanib; Behavioral: Quality of Life Assessment

Temsirolimus

EXPERIMENTAL

Temsirolimus 25 mg by vein infused over 30-60 minutes weekly. Benadryl 25 to 50 mg by vein approximately 30 minutes before the start of each dose of temsirolimus. Quality of Life Assessment - Completion of full assessment battery at baseline, prior to treatment then every 8 weeks at clinical evaluation.

Drug: Temsirolimus; Behavioral: Quality of Life Assessment; Drug: Benadryl

Interventions

Pazopanib DRUG

800 mg by mouth daily in 4 week study cycle.

Also known as: GW786034

Pazopanib

Temsirolimus DRUG

25 mg by vein infused over 30-60 minutes every week in 4 week study cycle.

Also known as: CCI-779, Torisel

Temsirolimus

Quality of Life Assessment BEHAVIORAL

Completion of full assessment battery at baseline, prior to treatment then every 8 weeks at clinical evaluation.

Also known as: Questionnaires, Surveys

Pazopanib; Temsirolimus

Benadryl DRUG

25 to 50 mg by vein approximately 30 minutes before the start of each dose of temsirolimus.

Also known as: Diphenhydramine

Temsirolimus

Eligibility Criteria

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

You may qualify if:

• Pathologic confirmation of metastatic or locally advanced RCC with a major clear cell component.
• Measurable disease by RECIST criteria.
• Age \>/= 18 years
• ECOG performance status 0-2 or Karnofsky Performance Status \>/= 60%
• Meets criteria for poor-risk defined as 3 or more of the following: ECOG performance status 2, anemia (hemoglobin lower than reference range), elevated serum LDH \> 1.5x upper limit of normal (ULN), hypercalcemia (corrected serum calcium level \> upper limit of normal), time from initial RCC diagnosis to registration on this trial \< 1 year, and \> 1 metastatic organ sites.
• Adequate organ and marrow function within 14 days of registration as defined below: a) Absolute neutrophil count \>/=1,500/µL b) Platelets \>/=100,000/µL c) Hgb \>/= 9.0 g/dL (transfusion allowed) d) Renal: serum creatinine \</= 1.5 x ULN or calculated CrCl \>/= 40 cc/min and random urine protein:creatinine ratio (UPC) \< 1 or 24-hr urine protein \< 1g e) Liver: total bilirubin \</= 1.5 mg/dl; AST (SGOT) and ALT (SGPT) \</= 2.5 x ULN for subjects without evidence of liver metastases, \</= 5 x ULN for subjects with documented liver metastases f) INR \</= 1.2 x ULN; PTT \</= 1.5 x ULN. Therapeutic anticoagulation with warfarin is allowed if target INR \</= 3 on a stable dose of warfarin or on a stable dose of LMW heparin for \> 2 weeks (14 days) at time of randomization.
• Female patients of childbearing potential (not postmenopausal for at least 12 months and not surgically sterile) must have a negative serum or urine pregnancy test within 14 days of study registration. Pregnancy test must be repeated if performed \> 14 days before starting study drug.

You may not qualify if:

• Prior malignancy, except for non-melanoma skin cancer, in situ carcinoma of any site, or other cancers for which the patient has been adequately treated and disease free for 2 years
• Prior targeted therapy (anti-VEGF agents or mTOR inhibitors) including adjuvant therapy, and prior chemotherapy for mRCC. However, prior immunotherapy (cytokines or vaccines) is allowed.
• Any experimental drug while on this study; however, concomitant bone targeted therapy (bisphosphonates or the anti-RANK ligand denosumab) is allowed.
• Uncontrolled brain metastases and infections. Patients with brain metastases treated with Gamma Knife (GK) or whole brain radiation within 24 hours of registration.
• History of stroke within 6 months of registration
• Clinically significant cardiovascular disease, defined as myocardial infarction (or unstable angina) within 6 months of registration, New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac dysrhythmia refractory to medical management. However, treated and controlled or stable/not clinically significant cardiovascular disease is allowed per evaluation by cardiologist.
• Uncontrolled hypertension (home blood pressure readings are permitted) or prior history of hypertensive crisis or hypertensive encephalopathy; however, treatment of hypertension with medications is permitted.
• History of uncontrolled hemoptysis (\>/= 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
• Significant vascular disease including aortic aneurysm, aortic dissection.
• Symptomatic peripheral vascular disease
• Pregnancy
• HIV-positive patients receiving combination anti-retroviral therapy
• Coagulopathy or bleeding diathesis
• Concomitant treatment with rifampin, St. John's wort, or the cytochrome p450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or Phenobarbital)
• Major surgery within 28 days prior to registration

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Novartis: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.

  PMID: 37146227 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Kidney Neoplasms; Carcinoma, Renal Cell; Neoplasm Metastasis; Pathologic Complete Response

Interventions

pazopanib; temsirolimus; Surveys and Questionnaires; Diphenhydramine

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Progression; Disease Attributes

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Ethylamines; Amines; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Amado J. .Zurita-Saavedra, MD/ Associate Professor, Genitourinary Medical Oncology
• Organization: UT MD Anderson Cancer Center

azurita@mdanderson.org

713- 563-6966

Study Officials

• Amado Zurita, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: July 8, 2011
• First Posted: July 12, 2011
• Study Start: October 24, 2012
• Primary Completion: September 8, 2019
• Study Completion: September 8, 2019
• Last Updated: September 20, 2021
• Results First Posted: September 20, 2021

Record last verified: 2021-08

Locations

US (1)