E7080 in Combination With Carboplatin + Gemcitabine Versus Carboplatin + Gemcitabine Alone as Second Line Therapy in Patients With Platinum-Sensitive Recurrent Ovarian Cancer by CA125

This study has been terminated.
(No participants)
Sponsor:
Collaborator:
PharmaBio Development Inc.
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01133756
First received: May 21, 2010
Last updated: May 21, 2013
Last verified: March 2013
  Purpose

The purpose of this study is to determine the MTD/recommended Phase II dose of E7080 administered in combination with carboplatin and gemcitabine (Phase IB) and to evaluate the safety and tolerability of E7080 administered in combination with carboplatin and gemcitabine compared to carboplatin and gemcitabine alone. (Phase II)


Condition Intervention Phase
Ovarian Cancer
Drug: E7080
Drug: Carboplatin + Gemcitabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Randomized, Phase Ib/II Study of E7080 in Combination With Carboplatin + Gemcitabine Versus Carboplatin + Gemcitabine Alone as Second Line Therapy in Patients With Platinum-Sensitive Recurrent Ovarian Cancer by CA125.

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Safety Parameter: Adverse Events [ Time Frame: Until study termination; 3 years ] [ Designated as safety issue: Yes ]
    Phase 1B: To determine the MTD of E7080 in combination with carboplatin and gemcitabine as determined by occurrence of dose-limiting toxicity at 3 ascending dose levels of E7080. Phase II: Safety and tolerability of E7080 at the MTD determined in Phase Ib in combination with carboplatin and gemcitabine as measured by rate of adverse events by body system and grade.

  • Safety Parameter: Concomitant Meds [ Time Frame: Until Study Termination; 3 years ] [ Designated as safety issue: Yes ]
    Phase 1B: To determine the MTD of E7080 in combination with carboplatin and gemcitabine as determined by occurrence of dose-limiting toxicity at 3 ascending dose levels of E7080. Phase II: Safety and tolerability of E7080 at the MTD determined in Phase Ib in combination with carboplatin and gemcitabine as measured by rate of adverse events by body system and grade.

  • Safety Parameter: Vital Signs [ Time Frame: Until study termination; 3 years ] [ Designated as safety issue: Yes ]
    Phase 1B: To determine the MTD of E7080 in combination with carboplatin and gemcitabine as determined by occurrence of dose-limiting toxicity at 3 ascending dose levels of E7080. Phase II: Safety and tolerability of E7080 at the MTD determined in Phase Ib in combination with carboplatin and gemcitabine as measured by rate of adverse events by body system and grade.

  • Safety Parameter: Lab Tests [ Time Frame: Days 1 and 28 of every cycle until study termination; 3 years ] [ Designated as safety issue: Yes ]
    Phase 1B: To determine the MTD of E7080 in combination with carboplatin and gemcitabine as determined by occurrence of dose-limiting toxicity at 3 ascending dose levels of E7080. Phase II: Safety and tolerability of E7080 at the MTD determined in Phase Ib in combination with carboplatin and gemcitabine as measured by rate of adverse events by body system and grade.

  • Safety Parameter: ECGs [ Time Frame: Day 1 and 30 days after termination of therapy; 3 years ] [ Designated as safety issue: Yes ]
    Phase 1B: To determine the MTD of E7080 in combination with carboplatin and gemcitabine as determined by occurrence of dose-limiting toxicity at 3 ascending dose levels of E7080. Phase II: Safety and tolerability of E7080 at the MTD determined in Phase Ib in combination with carboplatin and gemcitabine as measured by rate of adverse events by body system and grade.


Secondary Outcome Measures:
  • Efficacy Parameter [ Time Frame: Biomarker-based proportion of B-PFS at Week 12, within treatment group; [Timeframe: Week 12] ] [ Designated as safety issue: No ]
    Phase 1B: To determine the MTD of E7080 in combination with carboplatin and gemcitabine as determined by occurrence of dose-limiting toxicity at 3 ascending dose levels of E7080. Phase II: Safety and tolerability of E7080 at the MTD determined in Phase Ib in combination with carboplatin and gemcitabine as measured by rate of adverse events by body system and grade.

  • Efficacy Parameter [ Time Frame: Biomarker CA125-based overall response rate (B-ORR), within treatment group; [Timeframe: Day 1 of every cycle, at end of treatment visit and every 2 months during follow-up period for patients who complete study without PD] ] [ Designated as safety issue: No ]
    Phase 1B: To determine the MTD of E7080 in combination with carboplatin and gemcitabine as determined by occurrence of dose-limiting toxicity at 3 ascending dose levels of E7080. Phase II: Safety and tolerability of E7080 at the MTD determined in Phase Ib in combination with carboplatin and gemcitabine as measured by rate of adverse events by body system and grade.


Enrollment: 7
Study Start Date: March 2010
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: E7080
Carboplatin + Gemcitabine + E7080.
Drug: E7080

Test product: dose and mode of administration:

E7080 will be provided as 1 mg, 4 mg, and 10 mg tablets. E7080 will be self-administered orally by patients, once-daily, over 3 weeks during each cycle. For the Phase Ib portion, the dose will be 16 mg, 20 mg, or 24 mg and for the Phase II portion, the dose will be the MTD as determined in the Phase Ib portion of the study.

Number of cycles of E7080: until progression or unacceptable toxicity develops.

Other Name: Gemzar; Paraplatin
Drug: Carboplatin + Gemcitabine

Comparator dose and mode of administration: Gemcitabine (1000 mg/m2) given by IV infusion over 30 minutes on Day 1 and Day 8 of a 21-day cycle. Carboplatin (AUC 4) given by IV infusion over 30 minutes on Day 1 of a 21-day cycle.

Number of cycles: approximately 6.

Active Comparator: 1
Carboplatin + Gemcitabine
Drug: Carboplatin + Gemcitabine

Comparator dose and mode of administration: Gemcitabine (1000 mg/m2) given by IV infusion over 30 minutes on Day 1 and Day 8 of a 21-day cycle. Carboplatin (AUC 4) given by IV infusion over 30 minutes on Day 1 of a 21-day cycle.

Number of cycles: approximately 6.


Detailed Description:

This open-label, multicenter, randomized study will consist of a Phase Ib portion: a safety run-in period with 3 ascending doses of E7080 administered in combination with carboplatin + gemcitabine; and a Phase II portion: a randomized 2-arm period. Approximately 100 patients with ovarian cancer will be enrolled in the study (10-20 patients in the Phase Ib portion and 80 patients in the Phase II portion). Patients will only participate in either the Phase Ib or the Phase II portion. Patients will receive study treatment (E7080 plus carboplatin + gemcitabine or carboplatin + gemcitabine) for approximately six 21-day cycles (18 weeks). Patients who receive E7080 and experience evidence of clinical benefit (CR, PR, or SD) may continue single agent E7080 beyond 18 weeks, until the occurrence of progressive disease (PD), unacceptable toxicity, withdrawal of consent, or withdrawal by investigator, whichever occurs first.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects may be in the study only if they meet all of the following criteria.

  1. Female patients greater than or equal to 18 years of age.
  2. Histologically or cytologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer that was treated with and was sensitive to one prior platinum-based chemotherapy regimen for Stage III or Stage IV disease.
  3. Documentation of biochemical relapse defined by CA125 criteria (measurable or non-measurable by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST criteria), more than six months since completion of first-line platinum-based chemotherapy requiring treatment with further platinum-based chemotherapy. CA125 criteria for relapse Gynecologic Cancer Intergroup (GCIG) criteria are the finding of 2 serum CA125 levels with samples taken at least 1 week apart and no greater than 3 months apart:

    • greater than or equal to 2 x ULN in patients with an elevated pre-treatment serum CA125 level followed by normalization on treatment and prior to progression OR
    • greater than or equal to 2X nadir value for patients with an elevated pre-treatment CA125 that never normalizes).
  4. Gynecological Oncology Group performance status of 0 or 1
  5. Life expectancy greater than or equal to 3 months
  6. Patients must have recovered from effects of any major surgery within 28 days from the first dose of study treatment.
  7. Adequate hematologic, renal, liver, and coagulation system function as defined by laboratory values performed within 21 days prior to initiation of dosing.

    • Absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L
    • Platelet count greater than or equal to 100 x 109/L
    • Hemoglobin greater than or equal to 9 g/dL
    • Serum creatinine less than or equal to 1.5 X ULN and/or creatinine clearance 50 dL/min
    • Total serum bilirubin less than or equal to 1.5 X ULN
    • Serum aspartate transaminase (AST/SGOT) or serum alanine transaminase (ALT/SGPT) less than or equal to 2.5 X ULN, and less than or equal to 5 X ULN in cases of liver metastasis
    • PT/International normalized ratio (INR) less than or equal to 1.5 X ULN
    • PTT less than or equal to 1.1 X ULN
  8. Blood pressure must be well-controlled (less than or equal to 140/90 mmHg at screening) with or without antihypertensive medication. Patients must have no history of hypertensive crisis or hypertensive encephalopathy;
  9. Patients should have a negative pregnancy test at screening in pre-menopausal women and women less than 2 years after the onset of menopause. Pre-menopausal women must agree to use an acceptable method of birth control from the time of the negative pregnancy test up to 90 days after the last dose of study drug. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for greater than or equal to 1 year;
  10. Before study entry, written informed consent must be obtained from patient prior to performing any study-related procedures.

Exclusion Criteria:

Patients will not be entered in the study for any of the following reasons:

  1. Pregnant, breast-feeding, or refusing double barrier contraception, oral contraceptives or avoidance of pregnancy measures;
  2. Prior anti-angiogenic therapy with anti-VEGFR inhibitors; bevacizumab is allowed;
  3. Prior gemcitabine;
  4. Subjects with proteinuria greater than 1+ on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with 24-hour urine protein greater than or equal to 1 g/24 hours will be ineligible.
  5. Ovarian nonepithelial cancer, including malignant mixed Müllerian tumors and borderline tumors (e.g., tumors of low malignant potential);
  6. Other malignancy within 5 years of randomization, with the exception of adequately treated carcinoma in situ of the cervix or non-melanoma skin cancer, with no subsequent evidence of recurrence;
  7. History of, or known carcinomatous meningitis;
  8. Are currently receiving any other treatment for the tumor (including palliative radiotherapy) aside from control of symptoms;
  9. Received treatment in another clinical study within the 30 days prior to commencing study treatment or patients who have not recovered from side effects of an investigational drug to Grade less than or equal to 1, except for peripheral neuropathy (Grade 1 or 2 are permitted) or alopecia;
  10. Received chemotherapy, biological therapy, hormonal therapy, targeted therapy, or radiotherapy within the 30 days prior to commencing study treatment or have not recovered from all treatment-related toxicities to Grade less than or equal to 1, except for peripheral neuropathy (Grade 1 or 2 are permitted) or alopecia;
  11. Serious non-healing wound, ulcer, bone fracture, or have undergone a major surgical procedure, open biopsy, or significant traumatic injury within the 28 days prior to commencing study treatment. Minor surgery such as Portacath placement or skin biopsy is permitted if greater than or equal to 7 days have passed;
  12. The use of anti-coagulants such as Vitamin K antagonists, unfractionated heparin, or low molecular weight heparin;
  13. Refractory nausea and vomiting, malabsorption, significant bowel resection, or any other medical condition that would preclude adequate absorption or result in the inability to take oral medication;
  14. Significant cardiovascular impairment (history of congestive heart failure) New York Heart Association (NYHA) Grade II, unstable angina or myocardial infarction within the past 6 months, or serious cardiac arrhythmia);
  15. Any history of cerebral vascular accident (CVA) or transient ischemic attack (TIA) unless they have had no evidence of active disease for at least 6 months prior to randomization
  16. Active hemoptysis (defined as bright red blood of ½ teaspoon or more) within the 30 days prior to study entry;
  17. History of abdominal fistula, gastrointestinal perforation, or intrabdominal abscess within the 6 months prior to enrolment;
  18. History of bleeding diathesis or coagulopathy;
  19. History of an allograft requiring immunosuppression;
  20. Known positive human immunodeficiency virus (HIV), known surface antigen positive for hepatitis B hepatitis or C positive;
  21. Hypersensitivity to E7080 and/or E7080 chemical derivative; or
  22. Have any other uncontrolled infection or medical condition which would interfere with the conduct of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01133756

Locations
United States, Texas
Texas Oncology - Austin Central
Austin, Texas, United States, 78731
Sponsors and Collaborators
Eisai Inc.
PharmaBio Development Inc.
Investigators
Study Director: Harish Dave Quintiles
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01133756     History of Changes
Other Study ID Numbers: E7080-701, EURDACT NO 2009-016050-41
Study First Received: May 21, 2010
Last Updated: May 21, 2013
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Ukraine: State Pharmacological Center - Ministry of Health

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Gemcitabine
Carboplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on July 31, 2014