Alimta® Plus Cisplatin & Paclitaxel Given Intraperitonelly; First Line Tx Stage III Ovarian Cancer

NCT00702299 | Completed Phase 1 Results DMC

• 6 other identifiers: 07-0638-04P30CA023074UARIZ-07-0638-04UARIZ-SRC-18183LILLY-UARIZ-07-0638-04UARIZ-BIO07074
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Fallopian Tube Cancer; Ovarian Cancer; Peritoneal Cavity Cancer

Keywords

stage III ovarian epithelial cancer; recurrent ovarian epithelial cancer; peritoneal cavity cancer; fallopian tube cancer

Outcome Measures

Primary Outcomes (3)

• Maximum-tolerated Dose of Pemetrexed With a Day 2 i.p. Cisplatin (75 mg/m2) and Day 8 i.p. Paclitaxel (60 mg/m2)

  If none of the initial 3 patients on a dose level experienced a dose-limiting toxicity (DLT) after the first cycle of therapy, then the dose was escalated to the next level. If 2 or more patients on any dose level experienced a DLT, then the maximum tolerated dose would be determined to be the next lower dose level.

  18 months

• 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

  If none of the initial 3 patients on a dose level experienced a dose-limiting toxicity (DLT) after the first cycle of therapy, then the dose was escalated to the next level. If 2 or more patients on any dose level experienced a DLT, then the Maximum Tolerance Dose (MTD) would be determined to be the next lower dose level.

  18 months

• Patients Experienced Grade >=3 Toxicity at Dose Level 5 (1,000 mg/m2 IP Pemetrexed)

  Toxicity was assessed by NCI Common Toxicity Criteria for Adverse Effects v3.0

  18 months

Secondary Outcomes (3)

• Progression-free Survival at 18 Months as Assessed by Cancer Antigen 125

  18 months

• Overall Survival

  Average Length of follow-up 788 days

• Pharmacokinetics (Mean Cmax, ug/mL)for Different Dosages of Pemetrexed

  18 months

Study Arms (1)

Receiving Treatment

EXPERIMENTAL

Dose escalation of day 1 i.p. pemetrexed disodium accrued three patients to each of five dose levels (60-1,000 mg/m2), along with day 2 i.p. cisplatin (75 mg/m2) and day 8 i.p. paclitaxel (60 mg/m2) with a biologic sample preservation procedure

Drug: cisplatin; Drug: paclitaxel; Drug: pemetrexed disodium; Other: biologic sample preservation procedure

Interventions

cisplatin DRUG

IP cisplatin will be administered on day 2 of each cycle at 75mg per m2 and IP paclitaxel will be administered at 60mg per m2 on day 8 of each cycle. Courses will be repeated every 21 days for up to 6 cycles

Also known as: IP cisplatin

Receiving Treatment

paclitaxel DRUG

IP cisplatin will be administered on day 2 of each cycle at 75mg per m2 and IP paclitaxel will be administered at 60mg per m2 on day 8 of each cycle. Courses will be repeated every 21 days for up to 6 cycles

Also known as: IP paclitaxel

Receiving Treatment

pemetrexed disodium DRUG

Escalate doses in groups of 3 patients to 60mg per m2, 120 mg per m2, 500 mg per m2, 750 mg per m2, 1000 mg per m2

Also known as: Alimta

Receiving Treatment

biologic sample preservation procedure OTHER

Plasma samples will be collected on the 1st course at baseline, 30 minutes, 60 minutes, 2 hours, 4 hours, 6 hours (if possible) and 24 hours after the first IP Alimta® dose.

Receiving Treatment

Eligibility Criteria

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

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 antineoplastic or antitumor agents not part of the study therapy (i.e., chemotherapy, radiotherapy, immunotherapy, or hormonal anticancer therapy) * No other concurrent investigational agents

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Arizona: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Arizona Oncology - Scottsdale

Scottsdale, Arizona, 85258, United States

Location

Arizona Cancer Center at University of Arizona Health Sciences Center

Tucson, Arizona, 85724-5024, United States

Location

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial

Interventions

Cisplatin; Paclitaxel; Pemetrexed

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; 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

Limitations and Caveats

A limitation of this study is that max treatment dose was not definitively determined, in that the trial did not proceed at accrue patients at a dose level less than 1,000 mg/m2.

Results Point of Contact

• Title: Dr. Setsuko Chambers
• Organization: University of Arizona

schambers@azcc.arizona.edu

520/626.0950

Study Officials

• Setsuko K. Chambers, MD

  University of Arizona

  STUDY CHAIR

• David S. Alberts, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

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 19, 2008
• First Posted: June 20, 2008
• Study Start: September 1, 2007
• Primary Completion: January 1, 2012
• Study Completion: October 1, 2012
• Last Updated: January 1, 2016
• Results First Posted: July 19, 2013

Record last verified: 2015-12

Locations

US (2)