Pemetrexed Disodium in Treating Patients With Recurrent or Persistent Low-Risk Gestational Trophoblastic Tumor After a Molar Pregnancy

A Phase II Trial of Pemetrexed (ALIMTA®, LY231514, IND #40061) as Salvage Therapy for Failed Low Risk Gestational Trophoblastic Tumor

RATIONALE: Drugs used in chemotherapy, such as pemetrexed disodium, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying how well pemetrexed disodium works in treating patients with recurrent or persistent low-risk gestational trophoblastic tumor after a molar pregnancy.

Study Overview

• Status: Terminated
• Conditions: Gestational Trophoblastic Tumor
• Intervention / Treatment: Drug: pemetrexed disodium

Detailed Description

OBJECTIVES:

• Determine the activity of pemetrexed disodium as salvage therapy in patients with persistent or recurrent low-risk post-molar gestational trophoblastic tumor that failed prior dactinomycin or methotrexate.
• Determine the toxicity of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression or until tumor marker levels (human chorionic gonadotropin [hCG]) become normal. Patients receive 2 additional courses beyond the attainment of a normal hCG.

Beginning 7 days before and continuing until 3 weeks after the last dose of pemetrexed disodium, patients also receive oral folic acid daily and cyanocobalamin (vitamin B_12) intramuscularly every 9 weeks.

Patients are followed every 2 weeks for 2 months and then monthly for 10 months.

PROJECTED ACCRUAL: Approximately 17-55 patients will be accrued for this study within 20-50 months.

• Study Type: Interventional
• Enrollment (Anticipated): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center - Burbank
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611-3013
      • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
    • Hinsdale, Illinois, United States, 60521
      • Hinsdale Hematology Oncology Associates
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Holden Comprehensive Cancer Center at University of Iowa
  • Missouri
    • Springfield, Missouri, United States, 65804
      • St. John's Regional Health Center
    • Springfield, Missouri, United States, 65807
      • Hulston Cancer Center at Cox Medical Center South
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Cancer Institute of New Jersey at Cooper - Voorhees
  • North Carolina
    • Charlotte, North Carolina, United States, 28232-2861
      • Blumenthal Cancer Center at Carolinas Medical Center
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Wilson, North Carolina, United States, 27893-3428
      • Wilson Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Charles M. Barrett Cancer Center at University Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Cleveland, Ohio, United States, 44106
      • Case Comprehensive Cancer Center
    • Columbus, Ohio, United States, 43210-1240
      • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
    • Columbus, Ohio, United States, 43214-3998
      • Riverside Methodist Hospital Cancer Care
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Cancer Center at Hillcrest Hospital
    • Mentor, Ohio, United States, 44060
      • Lake/University Ireland Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Cancer Institute
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Rosenfeld Cancer Center at Abington Memorial Hospital
    • Reading, Pennsylvania, United States, 19612-6052
      • McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
    • Lubbock, Texas, United States, 79415-3364
      • UMC Southwest Cancer and Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 120 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS:

• Diagnosis of low-risk post-molar gestational trophoblastic tumor, defined as 1 of the following:

  • Increasing human chorionic gonadotropin (hCG) levels on ≥ 3 consecutive measurements taken over ≥ a 2-week period
  • Less than 10% decrease of hCG levels on 4 measurements taken over ≥ a 3-week period
• Persistent or recurrent disease

• Histologically confirmed complete or partial mole on initial evacuation

  • Prior pregnancy ≤ 12 months ago
• No histologically confirmed choriocarcinoma or placental site trophoblastic tumor on initial evacuation
• Failed only 1 prior dactinomycin or methotrexate therapy (with or without leucovorin calcium)
• WHO score 2-6

• No evidence of metastatic disease, except to the lung or vagina, on physical exam, chemistry, chest X-ray, and ultrasound

  • No liver, spleen, brain, kidney, or gastrointestinal tract metastases
  • No more than 8 metastatic lesions

PATIENT CHARACTERISTICS:

Age

• Any age

Performance status

• GOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Granulocyte count ≥ 1,500/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• SGOT ≤ 3 times ULN
• Alkaline phosphatase ≤ 3 times ULN

Renal

• Creatinine ≤ 1.5 mg/dL
• Creatinine clearance ≥ 45 mL/min

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 3 months after study participation
• No significant infection
• No other invasive malignancy within the past 5 years except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent prophylactic filgrastim (G-CSF) unless for recurrent neutropenic complications
• No concurrent prophylactic thrombopoietic agents unless for recurrent grade 4 thrombocytopenia

Chemotherapy

• See Disease Characteristics
• At least 7 days since prior dactinomycin or methotrexate (with or without leucovorin calcium) and recovered
• No prior pemetrexed disodium
• No other prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• At least 14 days since prior radiotherapy and recovered
• No prior radiotherapy to ≥ 25% of the bone marrow

Surgery

• Recovered from prior surgery

Other

• No nonsteroidal anti-inflammatory drugs or salicylates for 2 days (or 5 days for drugs with a long half-life) before, during, and for 2 days after pemetrexed disodium administration

  • Concurrent low-dose aspirin (≤ 325 mg/day) allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Toxicity
Activity

Collaborators and Investigators

• Sponsor: Gynecologic Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Allan Covens, MD, Toronto Sunnybrook Regional Cancer Centre

Study record dates

Study Major Dates

• Study Start: July 1, 2005
• Primary Completion (Actual): July 23, 2007

Study Registration Dates

• First Submitted: November 9, 2004
• First Submitted That Met QC Criteria: November 8, 2004
• First Posted (Estimate): November 9, 2004

Study Record Updates

• Last Update Posted (Actual): April 12, 2018
• Last Update Submitted That Met QC Criteria: April 11, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: recurrent gestational trophoblastic tumor; low risk metastatic gestational trophoblastic tumor; nonmetastatic gestational trophoblastic tumor
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Germ Cell and Embryonal; Pregnancy Complications; Pregnancy Complications, Neoplastic; Trophoblastic Neoplasms; Gestational Trophoblastic Disease; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Pemetrexed
• Other Study ID Numbers: CDR0000390347; GOG-0217; GOG-UC0205; LILLY-H3E-US-JMGR