Phase I Study of Vorinostat and Sorafenib in Advanced Cancer

NCT00635791 | Completed Phase 1 DMC

• 2 other identifiers: 07-0537.ccNCI-2013-00413
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of giving vorinostat and sorafenib tosylate together in treating patients with kidney or non-small cell lung cancer. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib tosylate may stop the growth of solid tumors by blocking blood flow to the tumor. Giving vorinostat together with sorafenib tosylate may kill more tumor cells.

Conditions

Malignant Solid Tumour; Renal Cell Carcinoma; Non Small Cell Lung Carcinoma

Keywords

Malignant Solid Tumour; Renal cell carcinoma; Non small cell lung carcinoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  The primary objective of this study is to determine the MTD for vorinostat in combination with the recommended dose of sorafenib 400 mg when given daily in a 21-day cycle and thereby establish a recommended Phase 2 dose of the combinations when administered daily in patients with advanced solid tumors

  Up to 21 days

Study Arms (1)

Sorafenib tosylate and vorinostat

EXPERIMENTAL

Patients receive sorafenib tosylate by mouth twice a day on days 1-21 and vorinostat by mouth every day on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Sorafenib; Drug: Vorinostat

Interventions

Sorafenib DRUG

Given by mouth

Also known as: NexAVAR

Sorafenib tosylate and vorinostat

Vorinostat DRUG

Given by mouth

Also known as: Zolinza

Sorafenib tosylate and vorinostat

Eligibility Criteria

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

You may qualify if:

• Parts A: Histologically or cytologically documented solid tumor malignancy or non-Hodgkin's lymphoma (Part B: renal cell carcinoma, Part C: non-small cell lung carcinoma) with clinical evidence of advanced and/or metastatic disease, which is refractory to established forms of therapy or for which no effective therapy exists, or for which sorafenib alone would be considered by the investigator as an appropriate therapy; patients who have refused available standard therapies would also be deemed eligible
• In Part A, evaluable disease by radiology and/or a recognized serum tumor marker is required; in Parts B and C, measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) is required
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
• Predicted life expectancy ≥ 12 weeks
• Patients may have had prior therapy, providing the following conditions are met:
• Patients must have recovered from any treatment related toxicities (with the exception of alopecia) to ≤ CTC grade 1 (fatigue, and neurotoxicity at grade 2 are permissible if stable for \> 3 months) prior to registration
• Chemotherapy: A minimum of 5 predicted half-lives of the agent must have elapsed between the end of treatment and registration on to the study; when half-lives are not available the principle of 2 weeks for once daily medications and 3 weeks for agents given less frequently will be adopted, but discussion with the principal investigator is recommended
• Hormonal therapy: Patients may have had prior anticancer hormonal therapy provided it is discontinued \> 4 weeks prior to registration into the study; however, patients with prostate cancer with evidence of progressive disease may continue on therapy which produces medical castration (eg, goserelin or leuprorelin) provided this was commenced at least three months earlier
• Radiation: Patients may have had prior radiation therapy that has not exceeded 25% of bone marrow reserve provided that they have recovered from the acute, toxic effects of radiotherapy prior to registration; a minimum of 7 days must have elapsed between the end of radiotherapy to non-target lesions and registration into the study (minimum of 28 days for target lesions)
• Surgery: Previous surgery is permitted provided that wound healing has occurred prior to registration
• Supportive therapy including bisphosphonates is permissible; previous use of myeloid and erythroid growth factor support is permissible, but not within 2 weeks of commencement of study; primary prophylactic use of myeloid and erythroid growth factors is not permitted within the study, but intervention or secondary prophylaxis is permitted if instituted following the documentation of ≥ grade 3 neutropenia or ≥ grade 2 anemia (hemoglobin)
• International Normalized Ratio (INR) \< 1.5 or a prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits; patients receiving anticoagulation treatment with an agent such as warfarin or heparin may be allowed to participate; for patients on warfarin, the INR should be measured prior to initiation of sorafenib/vorinostat and monitored at least weekly, or as defined by the local standard of care, until INR is stable; vorinostat and sorafenib have both been reported to elevate INR in those on coumadin derivatives
• Neutrophil count ≥ 1.5 x 10\^9/L
• Platelet count ≥ 75 x 10\^9/L
• Bilirubin ≤ 1.5 x Upper limit of normal (ULN)

You may not qualify if:

• Active or uncontrolled infections or serious illnesses or medical conditions that could interfere with the patient's ongoing participation in the study
• History of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent
• Concurrent anticancer therapy (with the exception of hormonal therapies as discussed above)
• Pregnant or breast-feeding females (documented methods of birth control are required in those with reproductive potential)
• Symptomatic brain metastases which are not stable, require steroids, or anti-epileptic medication
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs
• History of grade 3 or greater toxicities with vorinostat or sorafenib previously at equivalent daily doses or lower than those planned on being administered within this study
• Exposure to other histone deacetylase (HDAC) inhibitors (e.g. sodium valproate) within 30 days of planned commencement of study drugs, other exposures to HDAC inhibitor and sorafenib in combination
• Uncontrolled hypertension defined as systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management
• Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
• Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months
• Pulmonary hemorrhage/bleeding event \>= Common Toxicity Criteria for Adverse EffectS (CTCAE) grade 2 within 4 weeks of first dose of study drug
• Any other hemorrhage/bleeding event \>= CTCAE grade 3 within 4 weeks of first dose of study drug
• Serious non-healing wound, ulcer, or bone fracture
• Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Merck Sharp & Dohme LLC: collaborator
• Bayer: collaborator

Study Sites (1)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung

Interventions

Sorafenib; Vorinostat

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; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Anilides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• David R Camidge, MD, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

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: March 7, 2008
• First Posted: March 14, 2008
• Study Start: March 1, 2008
• Primary Completion: October 1, 2011
• Study Completion: March 1, 2012
• Last Updated: June 20, 2013

Record last verified: 2013-06

Locations

US (1)