Personalized Targeted Inhibitors Treatment in Renal Cell Cancer

NCT ID: NCT02560012

Last Updated: 2018-10-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-04
• Study Completion Date: 2017-07-27

Brief Summary

This is for subjects with metastatic Renal Cell Cancer (RCC). There are four Food and Drug Administration (FDA) approved drugs for first-line therapy of Renal Cell Cancer (RCC) and two for second-line therapy. Each of these drugs targets a specific molecular pathway. At present oncologists select therapy based on current guidelines. There is a new method for trying to use biomarker information from the subject's tumor to select the best drug to treat the subject. This process is investigational, which is why this study is being done.

Biomarkers are genes, proteins and other molecules that affect how cancer cells grow, multiply, die and respond to other compounds in the body. These biomarkers build a tumor profile or "fingerprint" of the subject's tumor. A new focus in cancer care is personalized treatment, where doctors select a drug based on the subject's tumor's unique "fingerprint" which is more likely to be effective in fighting the tumor. Selecting the treatment the subject is more likely to respond to requires a thorough understanding of the relationship between biomarker and treatment effect. The PI wants to gather data to understand that relationship to help treat future cancer patients. The purpose of this study is to evaluate efficacy of treatments that are selected based on tumor profiles.

Detailed Description

This will be a prospective, one-arm, proof of concept study designed to evaluate the efficacy of algorithm-based allocation (based on genomic/proteomic profile) of first-line therapy in renal cell carcinoma (RCC).

After eligibility review, patients will receive one of the four first-line therapy agents based on their tumor's molecular profile as determined using fresh biopsy tissue from an accessible metastatic site. Upon disease progression, patients will then receive one of two second-line agents based on their tumor's molecular profile.

Because this is a proof-of-concept study, the sample size is based on feasibility of accrual. The clinic should be able to recruit 100 patients within a reasonable timeframe for the study. The number of patients receiving each drug will vary based on the frequency of molecular alterations in the population. Therefore, groups will not be compared with one another - the research goal is to determine whether the progression-free survival (PFS) for each drug is improved over the PFS reported in FDA approval trials for each drug when they are assigned based on molecular analysis.

Conditions

Carcinoma, Renal Cell

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Personalized therapy

Subjects will receive one of the four first-line therapy agents based on their tumor's profile. The first-line agents are sunitinib, temsirolimus, sorafenib, or pazopanib. These are all routine drugs for RCC treatment and will be given at their approved doses and dosing schedules.

Upon disease progression, subject's tumor(s) will be biopsied again to create another tumor profile. The second-line agents are everolimus or axitinib. Both of these are routine drugs for RCC treatment and will be given at their approved doses and dosing schedules.

Group Type: OTHER

Sunitinib

Intervention Type: DRUG

One 50-mg capsule taken orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off

Temsirolimus

Intervention Type: DRUG

25 mg by an IV infusion over 30-60 minutes, once a week

Sorafenib

Intervention Type: DRUG

400 mg (2 tablets) orally twice daily without food

Pazopanib

Intervention Type: DRUG

800 mg orally once a day without food, at least 1 hour before or 2 hours after a meal

Everolimus

Intervention Type: DRUG

10 mg orally once daily with or without food

Axitinib

Intervention Type: DRUG

5 mg orally twice daily

Interventions

Sunitinib

One 50-mg capsule taken orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off

Intervention Type: DRUG

Temsirolimus

25 mg by an IV infusion over 30-60 minutes, once a week

Intervention Type: DRUG

Sorafenib

400 mg (2 tablets) orally twice daily without food

Intervention Type: DRUG

Pazopanib

800 mg orally once a day without food, at least 1 hour before or 2 hours after a meal

Intervention Type: DRUG

Everolimus

10 mg orally once daily with or without food

Intervention Type: DRUG

Axitinib

5 mg orally twice daily

Intervention Type: DRUG

Other Intervention Names

Sutent; Torisel; Nexavar; Votrient; Afinitor; Inlyta

Eligibility Criteria

Inclusion Criteria

• Pathologically confirmed renal cell carcinoma.
• No prior systemic and/or investigative therapy of any kind.

• Patients with primary tumor in place are strongly encouraged to undergo nephrectomy prior to initiation of study agent.
• Prior palliative radiotherapy to metastatic lesion(s) is permitted. Patient must have adequately recovered from the acute toxicities of this treatment.
• All major surgery of any type and/or radiotherapy must be completed at least 4 weeks prior to registration.
• Must have progressive metastatic disease
• ECOG performance status ≤2
• Women of childbearing potential and male patients must use acceptable methods of contraception-tubal ligation, vasectomy, barrier contraceptive with spermicide-while on study and for 3 months after the last dose of study therapy. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study.
• Age ≥18 years
• Required Initial Laboratory Values:

• Granulocytes ≥1,500/µL
• Platelet Count ≥100,000/µL
• Hemoglobin ≥9 g/dL
• AST/ALT ≤ 2.5 times the upper limit of normal (ULN)
• Alk. Phos.≤ 2.5 x ULN
• Serum bilirubin ≤ 1.5 x ULN
• Amylase/Lipase within normal range
• Urinalysis≤ 1+ protein
• T3T4 TSH - within normal range
• Pregnancy test for women - Negative
• Serum creatinine ≤ 1.5 x ULN
• Electrocardiogram (ECG) - no active ischemia
• Echocardiogram ejection fraction ≥40%
• Pulmonary function tests
• Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
• Signed informed consent prior to the performance of any study-specific procedures

Exclusion Criteria

• Ongoing hemoptysis, or cerebrovascular accident within 12 months prior to study entry, or peripheral vascular disease with claudication occurring upon walking less than one city block, or history of clinically significant bleeding.
• Deep venous thrombosis or pulmonary embolus within 12 months prior to study entry and no ongoing need for full-dose oral or parenteral anticoagulation. For maintenance of catheter patency daily prophylactic aspirin or low-dose coumadin (1-2 mg) is allowed.
• Evidence of current central nervous system (CNS) metastases. All patients must undergo a CT scan of the brain (with contrast, if possible) within 42 days prior to registration. Any imaging abnormality indicative of active CNS metastases will exclude the patient from the study.
• Significant cardiovascular disease defined as congestive heart failure (New York Heart Association Class II, II or IV) angina pectoris requiring nitrate therapy, or recent myocardial infarction (within the preceding 6 months prior to study entry).
• Uncontrolled hypertension (defined as blood pressure of ≥160 mmHg systolic and/or ≥90 mmHg diastolic on medication). Document over 48 hours with minimum of 3 readings.
• Ongoing requirement for systemic corticosteroid therapy (except replacement therapy for adrenal insufficiency) or other immunosuppressants are not permitted. Topical and/or inhaled steroids are allowed.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

Robert J Amato

Director and Professor, Department of Internal Medicine, Division of Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robert Amato, DO

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

Locations

UTHealth Memorial Hermann Cancer Center

Houston, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HSC-14-0665

Identifier Type: OTHER

Identifier Source: secondary_id

GU-14-102

Identifier Type: -

Identifier Source: org_study_id