Sorafenib, Pemetrexed, And Cisplatin In Treating Patients With Advanced Solid Tumors

Study Overview

Sorafenib, Pemetrexed, and Cisplatin in Treating Patients With Advanced Solid Tumors

RATIONALE: Sorafenib and pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with pemetrexed and cisplatin may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of sorafenib when given together with pemetrexed and cisplatin in treating patients with advanced solid tumors.

OBJECTIVES: Primary * To determine the maximum tolerated dose of sorafenib tosylate when given in combination with pemetrexed disodium and cisplatin in patients with advanced non-squamous cell solid tumor malignancy including, but not limited to, breast, lung, colon, pancreatic, prostate, or head and neck cancer or sarcoma. Secondary * To characterize the quantitative and qualitative toxicities of this regimen in these patients. * To obtain preliminary information about the antitumor activity of this regimen in these patients. OUTLINE: This is a dose-escalation study of sorafenib tosylate. Patients receive oral sorafenib tosylate once daily on days 1-21 and cisplatin IV over 1-2 hours and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 30 days, every 8 weeks until disease progression, and then every 3 months for up to 6 months.

Breast Cancer
Colorectal Cancer
Head and Neck Cancer
Lung Cancer
Mesothelioma
Pancreatic Cancer
Prostate Cancer
Sarcoma

DRUG: cisplatin
DRUG: pemetrexed disodium
DRUG: sorafenib

2007LS086
0712M22703 (OTHER Identifier) (OTHER: IRB, University of Minnesota)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2008-06-20	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2017-11-27
First Submitted that Met QC Criteria 2008-06-20	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2017-11-29
First Posted (ACTUAL) 2008-06-23	Results First Posted N/A	Last Verified 2017-11

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Sorafenib/Pemetrexed/Cisplatin Patients receiving a dose escalation scheme of daily oral sorafenib (200 mg or 400 mg bid) when given in combination with fixed dose intravenous pemetrexed and cisplatin for the treatment of solid tumors.	DRUG: cisplatin Cisplatin administered intravenously, 75 mg/m^2 over 1-2 hours on day 1 of a 21 day cycle DRUG: pemetrexed disodium Pemetrexed 500 mg/m^2 intravenously (IV) will be given as a 10-minute intravenous infusion (after cisplatin) on day 1 of a 21 day cycle DRUG: sorafenib daily oral sorafenib (200 mg or 400 mg bid)

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Sorafenib/Pemetrexed/Cisplatin

Patients receiving a dose escalation scheme of daily oral sorafenib (200 mg or 400 mg bid) when given in combination with fixed dose intravenous pemetrexed and cisplatin for the treatment of solid tumors.

DRUG: cisplatin

Cisplatin administered intravenously, 75 mg/m^2 over 1-2 hours on day 1 of a 21 day cycle

DRUG: pemetrexed disodium

Pemetrexed 500 mg/m^2 intravenously (IV) will be given as a 10-minute intravenous infusion (after cisplatin) on day 1 of a 21 day cycle

DRUG: sorafenib

daily oral sorafenib (200 mg or 400 mg bid)

Primary Outcome Measures	Measure Description	Time Frame
Maximum tolerated dose of sorafenib tosylate	This dose level is declared to be above the maximum tolerated dose (MTD) and dose escalation is stopped. Declare the next lower dose the MTD if 6 patients have already been treated at that dose.	From first dose to toxicity event

Secondary Outcome Measures	Measure Description	Time Frame
Disease Response	Each patient will be assigned one of the following Response Evaluation Criteria in Solid Tumors (RECIST) categories: * complete response; * partial response; * stable disease; * progressive disease; * early death from malignant disease; * unknown (insufficient evaluation to determine response status).	At 6- 8 weeks
Maximum, Minimum and AUC Concentrations of Sorafenib	Maximum and minimum serum concentrations and area under the concentration time curve (AUC) for sorafenib will be predicted using standard pharmacokinetic software	Day 1 to Day 8

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologic or cytologic diagnosis of advanced non-hematologic malignancy (except squamous cell of the lung) including, but not limited to breast, lung, colon, pancreatic, prostate, head and neck, or sarcoma
Must have failed or become intolerant to prior standard therapy and is no longer likely to respond to such therapy except for patients diagnosed with mesothelioma. Mesothelioma patients may be enrolled with no prior therapy requirements since cisplatin and pemetrexed in combination is the current standard of care 1st line therapy.
At least 21 days must have passed from previous systemic therapy (at least 6 weeks for prior bevacizumab) and the patient must have recovered from the all toxic effects of previous treatment prior to study enrollment. Prior treatment with cisplatin and/or pemetrexed is allowed, but at least 3 months must have passed since the last dose. Prior treatment with sorafenib is not allowed.
Prior radiation therapy is allowed except to the whole pelvis. At least 14 days from last radiation therapy treatment and must have recovered from the acute toxic effects prior to study enrollment.
Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2
18 years of age and older
Adequate organ function within 7 days of study enrollment including the following:

Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L; platelets ≥100 x 10^9/L; hemoglobin ≥ 9 g/dL
Hepatic: bilirubin ≤1.5 times the upper limit of normal (× ULN); alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 × ULN (ALP, AST, and ALT ≤ 5× ULN is acceptable if liver has tumor involvement)
Renal: serum creatinine ≤ 1.5 and calculated creatinine clearance > 45.

Males: cr cl (mL)/min) = weight (kg) x (140-age)divided by 72 x serum creatinine (mg/dL)
Females: cr cl (mL)/min) = weight (kg) x (140-age) x 0.85 divided by 72 x serum creatinine (mg/dL)

Coagulation: INR < 1.5 or a PT/PTT within normal limits
Patients receiving anti-coagulation 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 and monitored at least weekly, or as defined by the local standard of care, until INR is stable.

Women of childbearing potential and sexually active males are required to use an effective method of contraception (barrier method of birth control) during the study and for 2 weeks after the last dose of sorafenib.
Must be able to take folic acid and vitamin B12.
Must be able and willing to interrupt aspirin or other nonsteroidal antiinflammatory agents for a 5 day period (8 day period for long acting agents such as piroxicam) prior at the time of each pemetrexed administration.
Must be able to take oral medications without crushing, dissolving, or chewing tablets.
Voluntary written informed consent before performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Squamous cell of the lung
Pregnant (positive pregnancy test) or breast-feeding. Pemetrexed, cisplatin and sorafenib are pregnancy category D - clear evidence of risk in pregnancy. Women of child bearing potential must have a negative serum or urine pregnancy test within 7 days of prior to the start of treatment. Pregnancy testing is not required for postmenopausal or surgically sterilized women.
Cardiac disease: Congestive heart failure > class II New York Heart Association Classification (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
Symptomatic or active brain metastases. Patients with neurological symptoms or previously treated CNS metastases must undergo a CT scan/MRI of the brain within 14 days of study enrollment to rule-out brain metastasis.
The presence of clinically significant third space fluid such as pleural effusion or ascites. Patients in whom the third space fluid can be completely drained may be enrolled.
Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management
Known or suspected allergy to sorafenib, pemetrexed, cisplatin or any agent given in the course of this trial
Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C
Patients must not have a second primary malignancy except in situ carcinoma of the cervix or breast or other in situ malignancies or adequately treated basal cell carcinoma of the skin or other malignancy treated at least 3 years previously with no evidence of recurrence
Active clinically serious infection > Common Toxicity Criteria for Adverse Events (CTCAE) Grade 2
Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months
Pulmonary hemorrhage/bleeding event ≥ 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
Evidence or history of bleeding diathesis or coagulopathy
Peripheral neuropathy ≥ CTCAE Grade 2
Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug
Use of St. John's Wort or rifampin (rifampicin)
Any condition that impairs patient's ability to swallow whole pills
Any malabsorption problem

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Priya Kumar, MD, Masonic Cancer Center, University of Minnesota

Publications

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