Personalized Targeted Inhibitors Treatment in Renal Cell Cancer

NCT02560012 | Terminated Phase 2 Results DMC

• 2 other identifiers: GU-14-102HSC-14-0665
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Carcinoma, Renal Cell

Keywords

Renal Cell Carcinoma; RCC; Personalized therapy; targeted inhibitors

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Progressed

  The PFS is defined as the time elapsed between treatment initiation and tumor progression or death from any cause, with censoring of patients who are lost to follow-up. Progression is defined using the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1): " At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression)."

  From date of enrollment until the date of first documented progression, date of death from any cause, or date that the study was stopped, whichever came first, an average of 16 months

Study Arms (1)

Personalized therapy

OTHER

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.

Drug: Sunitinib; Drug: Temsirolimus; Drug: Sorafenib; Drug: Pazopanib; Drug: Everolimus; Drug: Axitinib

Interventions

Sunitinib DRUG

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

Also known as: Sutent

Personalized therapy

Temsirolimus DRUG

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

Also known as: Torisel

Personalized therapy

Sorafenib DRUG

400 mg (2 tablets) orally twice daily without food

Also known as: Nexavar

Personalized therapy

Pazopanib DRUG

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

Also known as: Votrient

Personalized therapy

Everolimus DRUG

10 mg orally once daily with or without food

Also known as: Afinitor

Personalized therapy

Axitinib DRUG

5 mg orally twice daily

Also known as: Inlyta

Personalized therapy

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead

Study Sites (1)

UTHealth Memorial Hermann Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Sunitinib; temsirolimus; Sorafenib; pazopanib; Everolimus; Axitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Sirolimus; Macrolides; Lactones; Benzamides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Indazoles; Pyrazoles

Results Point of Contact

• Title: Research Manager
• Organization: The University of Texas Health Science Center, Houston

Marka.Lyons@uth.tmc.edu

713-500-6919

Study Officials

• Robert Amato, DO

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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

Study Record Dates

• First Submitted: September 17, 2015
• First Posted: September 25, 2015
• Study Start: January 4, 2016
• Primary Completion: July 27, 2017
• Study Completion: July 27, 2017
• Last Updated: October 12, 2018
• Results First Posted: October 12, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)