Phase I Study of Sorafenib, Pemetrexed, and Cisplatin for the Treatment of Advanced Solid Tumors.
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Maximum tolerated dose of sorafenib tosylate
Study Overview
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.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- •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
Arms & Interventions
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.
Intervention: cisplatin (Drug)
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.
Intervention: pemetrexed disodium (Drug)
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.
Intervention: sorafenib (Drug)
Outcomes
Primary Outcomes
Maximum tolerated dose of sorafenib tosylate
Time Frame: From first dose to toxicity event
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.
Secondary Outcomes
- Maximum, Minimum and AUC Concentrations of Sorafenib(Day 1 to Day 8)
- Disease Response(At 6- 8 weeks)