Phase 1
N=15
Alimta® Plus Cisplatin & Paclitaxel Given Intraperitonelly; First Line Tx Stage III Ovarian Cancer
Fallopian Tube Cancer · Ovarian Cancer · Peritoneal Cavity Cancer
Bottom Line
View on ClinicalTrials.gov: NCT00702299 ↗Enrolled (actual)
15
Serious AEs
33.3%
Results posted
Jul 2013
Primary outcome: Primary: Maximum-tolerated Dose of Pemetrexed With a Day 2 i.p. Cisplatin (75 mg/m2) and Day 8 i.p. Paclitaxel (60 mg/m2) — 500 mg/m2
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- cisplatin (Drug); paclitaxel (Drug); pemetrexed disodium (Drug); biologic sample preservation procedure (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Female
- Sponsor
- University of Arizona
- Primary completion
- Jan 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum-tolerated Dose of Pemetrexed With a Day 2 i.p. Cisplatin (75 mg/m2) and Day 8 i.p. Paclitaxel (60 mg/m2) |
500 | — |
| PRIMARY Patients That Completed at Least 6 Courses of Therapy of Pemetrexed Along With Day 2 i.p. Cisplatin (75 mg/m2) and Day 8 i.p. Paclitaxel (60 mg/m2)at the Determined Maximum Tolerated Dose |
80.0 | — |
| PRIMARY Patients Experienced Grade >=3 Toxicity at Dose Level 5 (1,000 mg/m2 IP Pemetrexed) |
2 | — |
| SECONDARY Progression-free Survival at 18 Months as Assessed by Cancer Antigen 125 |
78.6 | — |
| SECONDARY Overall Survival |
680 | — |
| SECONDARY Pharmacokinetics (Mean Cmax, ug/mL)for Different Dosages of Pemetrexed |
25.1; 39.3; 38.7 | — |
Summary
RATIONALE: Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pemetrexed together with cisplatin and paclitaxel and giving them in different ways may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of intraperitoneal pemetrexed when given together with intraperitoneal cisplatin and paclitaxel in treating patients with stage III ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer.
Eligibility Criteria
DISEASE CHARACTERISTICS:
- Histologically or pathologically confirmed ovarian epithelial carcinoma, primary peritoneal carcinoma, or fallopian tube carcinoma
- Stage III disease
- Meets 1 of the following criteria:
- No prior treatment and no more than 6 months since primary surgery
- Platinum-sensitive at second-look surgery with no prior cisplatin therapy
- Must have been optimally debulked to less than 2-cm residual individual tumor plaques or, if suboptimally debulked at first surgery, had chemical debulking
- No mixed Müllerian tumor or borderline ovarian tumor
- No Central nervous system (CNS) or brain metastases
PATIENT CHARACTERISTICS:
- Gynecologic Oncology Group performance status 0-2
- White blood cell count(WBC) ≥ 3,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 9 g/dL
- Serum bilirubin ≤ 2 times upper limit of normal (ULN)
- Aspartate aminotransferase (AST)and alanine aminotransferase (ALT) ≤ 2.5 times upper limit of normal
- Creatinine clearance ≥ 45 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception during and for 3 months after discontinuation of study drug
- No psychological, familial, sociological, or geographical conditions that do not permit medical follow-up or compliance with the study protocol
- No unstable or preexisting major medical conditions, except cancer-related abnormalities
- No medical life-threatening complications of their malignancies
- No known severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease, active uncontrolled infection, or HIV)
- No serious active uncontrolled infections
- No inadequately controlled hypertension (defined as systolic blood pressure ≥ 150 mm Hg and/or diastolic blood pressure ≥ 100 mm Hg on antihypertensive medications)
- No New York Heart Association grade II-IV congestive heart failure
- No weight loss between 5 to ≤ 10% within the past 14 days that is not related to ascites or paracentesis
- No prior hypertensive crisis or hypertensive encephalopathy
- No myocardial infarction, cerebrovascular accident, transient ischemic attack, or unstable angina within the past 6 months
- No evidence of uncontrollable nausea
- No clinically significant or symptomatic peripheral vascular disease (e.g., aortic aneurysm or aortic dissection)
- No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
- No pre-existing clinically significant hearing loss
- No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ, or adequately treated stage I or II cancer from which the patient is in complete remission
- No known hypersensitivity to any component of pemetrexed disodium
- Able to take folic acid, vitamin B\_12, and dexamethasone according to protocol
- No presence of third-space fluid that cannot be controlled by drainage
- No inability to comply with study and/or follow-up procedures
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- May have received up to 4 courses of carboplatin and paclitaxel IV as neoadjuvant chemotherapy for advanced, unresectable disease
- Concurrent low-dose aspirin therapy (i.e., 325 mg/day) allowed
- Concurrent ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) with short elimination half-lives allowed provided ≥ 1 of the following criteria is met:
- Creatinine clearance (CrCl) > 80 mL/min (i.e., normal renal function)
- CrCl 45-79 mL/min (i.e., mild to moderate renal insufficiency) AND NSAID dosing interrupted for a period of 2 days before, during, and 2 days after administration of pemetrexed disodium
- Concurrent NSAIDs or salicylates with long half-lives (e.g., naproxen, piroxicam, diflunisal, or nabumetone) allowed provided NSAID dosing is interrupted for at least 5 days before, during, and 2 days after administration of pemetrexed disodium
- No concurrent antineo
Data sourced from ClinicalTrials.gov (NCT00702299). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.