Panobinostat and Everolimus in Treating Patients With Metastatic or Unresectable Renal Cell Cancer That Does Not Respond to Treatment With Sunitinib Malate or Sorafenib Tosylate

NCT01582009 | Terminated Phase 1 Results DMC

• 2 other identifiers: I146308NCI-2009-01599
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Panobinostat and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. PURPOSE: This phase I/II trial is studying the side effects and best dose of giving panobinostat together with everolimus and to see how well they work in treating patients with metastatic or unresectable renal cell cancer that does not respond to treatment with sunitinib malate or sorafenib tosylate

Conditions

Clear Cell Renal Cell Carcinoma; Recurrent Renal Cell Cancer; Stage III Renal Cell Cancer; Stage IV Renal Cell Cancer

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS)

  6 month PFS survival rate. Calculated as the total number of failures (deaths or progression) divided by the total follow-up or exposure time of patients on study. Assessed using Kaplan Meier and Proportional Hazards.

  The time from registration to documentation of disease progression up to 3 years

• Number of Participants With Clinical Response

  Number of participants with clinical response. Response will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors ver 1.0 Committee \[JNCI 92(3):205-216, 2000\]. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST ver. 1.0 criteria.

  The time from registration up to 3 years

Secondary Outcomes (3)

• Number of Participants With an Adverse Event.

  The time from registration up to 3 years

• Median Progression Free Survival

  The time from registration up to 3 years

• 6-month Overall Survival Rate

  The time from registration up to 3 years

Study Arms (1)

Arm I: Oral Panobinostat and Oral Everolimus

EXPERIMENTAL

Patients receive oral panobinostat once daily on days 1, 3, 4, 8, 10, and 12 and oral everolimus once daily on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: panobinostat; Drug: everolimus; Other: laboratory biomarker analysis; Other: pharmacological study; Other: liquid chromatography; Other: mass spectrometry; Other: enzyme-linked immunosorbent assay; Other: immunohistochemistry staining method

Interventions

panobinostat DRUG

Given orally

Also known as: Faridak, HDAC inhibitor LBH589, histone deacetylase inhibitor LBH589, LBH589

Arm I: Oral Panobinostat and Oral Everolimus

everolimus DRUG

Given orally

Also known as: 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001

Arm I: Oral Panobinostat and Oral Everolimus

laboratory biomarker analysis OTHER

Correlative studies

Arm I: Oral Panobinostat and Oral Everolimus

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I: Oral Panobinostat and Oral Everolimus

liquid chromatography OTHER

Correlative studies

Also known as: LC

Arm I: Oral Panobinostat and Oral Everolimus

mass spectrometry OTHER

Correlative studies

Arm I: Oral Panobinostat and Oral Everolimus

enzyme-linked immunosorbent assay OTHER

Correlative studies

Also known as: ELISA

Arm I: Oral Panobinostat and Oral Everolimus

immunohistochemistry staining method OTHER

Correlative studies

Also known as: immunohistochemistry

Arm I: Oral Panobinostat and Oral Everolimus

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed metastatic or unresectable renal cell carcinoma
• Predominant clear cell component is required
• Patients must have metastatic disease which has progressed on or within 6 months of stopping treatment with VEGFR receptor tyrosine kinase inhibitors
• Previous therapy with bevacizumab, interleukin 2, or interferon alpha is also permitted
• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
• Serum albumin \>= 3g/dL
• AST/SGOT and ALT/SGPT =\< 2.5 x upper limit of normal (ULN)
• Serum bilirubin =\< 1.5 x ULN
• Serum creatinine =\< 1.5 x ULN or 24-hour creatinine clearance \>= 50 ml/min
• Serum potassium \>= LLN
• Serum phosphorous \>= LLN
• Serum total calcium (corrected for serum albumin) or serum ionized calcium \>= LLN
• Serum magnesium \>= LLN
• TSH and free T4 within normal limits (WNL); patients may be on thyroid hormone replacement
• ANC \>= 1.5 x 10\^9/L

You may not qualify if:

• Pure papillary and chromophobe renal cell carcinoma, collecting duct tumors and transitional cell carcinoma are not eligible
• Prior treatment with a pan-HDAC or mTOR inhibitor
• Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.)
• Patients who have had a major surgery of significant traumatic injury within 4 weeks of start of study drug and who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
• Prior treatment with any investigational drug within the preceding 4 weeks
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent; topical or inhaled corticosteroids are allowed
• Patients should not receive immunization with attenuated live vaccines within one weeks of study entry or during study period; close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus (Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY2a typhoid vaccines)
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
• Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• \) Symptomatic congestive heart failure of New York Heart Association Class III or 4
• \) Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
• \) Concomitant use of drugs with a risk of causing torsades de pointes
• \) Severely impaired lung functions as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air
• \) Uncontrolled diabetes as defined by fasting serum glucose \> 1.5 x ULN; optimal glycemic control should be achieved before starting trial therapy

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Novartis: collaborator

Study Sites (2)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Related Publications (1)

• Wood A, George S, Adra N, Chintala S, Damayanti N, Pili R. Phase I study of the mTOR inhibitor everolimus in combination with the histone deacetylase inhibitor panobinostat in patients with advanced clear cell renal cell carcinoma. Invest New Drugs. 2020 Aug;38(4):1108-1116. doi: 10.1007/s10637-019-00864-7. Epub 2019 Oct 25.

  PMID: 31654285 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Panobinostat; Everolimus; Chromatography, Liquid; Mass Spectrometry; Enzyme-Linked Immunosorbent Assay; Immunohistochemistry

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)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sirolimus; Macrolides; Lactones; Chromatography; Chemistry Techniques, Analytical; Investigative Techniques; Immunoenzyme Techniques; Immunoassay; Immunologic Techniques; Immunosorbent Techniques; Molecular Probe Techniques; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques

Results Point of Contact

• Title: Senior Administrator, Compliance - Clinical Research Services
• Organization: Roswell Park Cancer Institute

716-845-2300

Study Officials

• Saby George, MD

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2010
• First Posted: April 20, 2012
• Study Start: March 1, 2010
• Primary Completion: October 1, 2015
• Study Completion: December 1, 2015
• Last Updated: August 15, 2022
• Results First Posted: May 17, 2017

Record last verified: 2022-08

Locations

US (2)