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

NCT00703638 | Completed Phase 1 DMC

• 2 other identifiers: 2007LS0860712M22703
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Disease Response

  At 6- 8 weeks

• Maximum, Minimum and AUC Concentrations of Sorafenib

  Day 1 to Day 8

Study Arms (1)

Sorafenib/Pemetrexed/Cisplatin

EXPERIMENTAL

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; Drug: pemetrexed disodium; Drug: sorafenib

Interventions

cisplatin DRUG

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

Also known as: CDDP, Platinol

Sorafenib/Pemetrexed/Cisplatin

pemetrexed disodium DRUG

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

Also known as: Alimta, MTA, LY231514

Sorafenib/Pemetrexed/Cisplatin

sorafenib DRUG

daily oral sorafenib (200 mg or 400 mg bid)

Also known as: BAY 43-9006 tosylate, NSC 724772

Sorafenib/Pemetrexed/Cisplatin

Eligibility Criteria

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

You may qualify if:

• 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
• 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.
• The creatinine clearance is determined by the Cockcroft-Gault formula:
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Colorectal Neoplasms; Head and Neck Neoplasms; Lung Neoplasms; Mesothelioma; Pancreatic Neoplasms; Prostatic Neoplasms; Sarcoma

Interventions

Cisplatin; Pemetrexed; Sorafenib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Mesothelial; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplasms, Connective and Soft Tissue

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Priya Kumar, MD

  Masonic Cancer Center, University of Minnesota

  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: June 20, 2008
• First Posted: June 23, 2008
• Study Start: May 1, 2008
• Primary Completion: September 1, 2010
• Study Completion: November 1, 2010
• Last Updated: November 29, 2017

Record last verified: 2017-11

Locations

US (1)