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

NCT01133756 | Terminated Phase 1 Results

• 2 other identifiers: E7080-7012009-016050-41
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study was to determine the maximum tolerated dose (MTD)/recommended Phase II dose of lenvatinib 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) in participants with platinum-sensitive recurrent ovarian cancer.

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose Limiting Toxicity (DLT)

  DLTs were defined as clinically significant adverse events occurring less than or equal to 21 days after commencing study treatment and considered to be possibly or probably related to study treatment by the Investigator. If 1 DLT occurred at any dose level, the cohort was to be expanded to include a maximum of six evaluable subjects. If 2 DLTs occurred at any dose level, the maximum tolerated dose (MTD) was to be either defined as the preceding dose, or an intermediate dose. To evaluate an intermediate dose, an additional dose cohort could be added to more accurately define the MTD.

  Cycle 1 (21 days)

Secondary Outcomes (2)

• Biomarker CA125-based Overall Response Rate (B-ORR), Within Treatment Group

  Day 1 of every cycle, at end of treatment visit and every 2 months during follow-up period for patients who complete study without progressive disease.

• Biomarker-based Proportion of Biomarker-Progression-Free Survival (B-PFS) at Week 12, Within Treatment Group

  Week 12

Study Arms (2)

Lenvatinib plus carboplatin + gemcitabine

EXPERIMENTAL

Phase IB and Phase II

Drug: Lenvatinib; Drug: Carboplatin; Drug: Gemcitabine

Carboplatin + gemcitabine

ACTIVE COMPARATOR

Phase II

Drug: Carboplatin; Drug: Gemcitabine

Interventions

Lenvatinib DRUG

lenvatinib (as 1mg, 4mg, and 10mg tablets) was administered orally, once daily continuously for each 21-day treatment cycle.

Also known as: Lenvima, E7080

Lenvatinib plus carboplatin + gemcitabine

Carboplatin DRUG

Carboplatin was to be administered on Day 1 of every 21-day cycle at a dose AUC 4 over 30 minutes.

Carboplatin + gemcitabine; Lenvatinib plus carboplatin + gemcitabine

Gemcitabine DRUG

Gemcitabine was to be administered on Day 1 and Day 8 of every 21-day cycle at a dose of 1000 mg/m2 over 30 minutes.

Carboplatin + gemcitabine; Lenvatinib plus carboplatin + gemcitabine

Eligibility Criteria

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

You may qualify if:

• Participants may be in the study only if they meet all of the following criteria.
• Female participants greater than or equal to 18 years of age.
• 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.
• 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 participants with an elevated pre-treatment serum CA125 level followed by normalization on treatment and prior to progression OR
• greater than or equal to 2 X nadir value for participants with an elevated pre-treatment CA125 that never normalizes).
• Gynecological Oncology Group performance status of 0 or 1
• Life expectancy greater than or equal to 3 months
• Participants must have recovered from effects of any major surgery within 28 days from the first dose of study treatment.
• 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

You may not qualify if:

• Participants will not be entered in the study for any of the following reasons:
• Pregnant, breast-feeding, or refusing double barrier contraception, oral contraceptives or avoidance of pregnancy measures;
• Prior anti-angiogenic therapy with anti-VEGFR inhibitors; bevacizumab is allowed;
• Prior gemcitabine;
• Participants with proteinuria greater than 1+ on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with 24-hour urine protein greater than or equal to 1 g/24 hours will be ineligible.
• Ovarian nonepithelial cancer, including malignant mixed Mullerian tumors and borderline tumors (e.g., tumors of low malignant potential);
• 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;
• History of, or known carcinomatous meningitis;
• Are currently receiving any other treatment for the tumor (including palliative radiotherapy) aside from control of symptoms;
• Received treatment in another clinical study within the 30 days prior to commencing study treatment or participants 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;
• 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;
• 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;
• The use of anti-coagulants such as Vitamin K antagonists, unfractionated heparin, or low molecular weight heparin;
• 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;
• 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);

Sponsors & Collaborators

• Eisai Inc.: lead
• PharmaBio Development Inc.: collaborator

Study Sites (1)

Texas Oncology - Austin Central

Austin, Texas, 78731, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

lenvatinib; Carboplatin; Gemcitabine

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Due to the limited enrollment despite significant diligence to boost enrollment and the complex study design required to manage hematologic toxicity, the study was terminated before the initiation of Phase 2.

Results Point of Contact

• Title: Eisai Medical Services
• Organization: Eisai Inc.

esi_medinfo@eisai.com

1-888-422-4743

Study Officials

• Harish Dave, MD

  Quintiles, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2010
• First Posted: May 31, 2010
• Study Start: March 1, 2010
• Primary Completion: February 1, 2012
• Study Completion: September 1, 2012
• Last Updated: June 22, 2023
• Results First Posted: December 5, 2016

Record last verified: 2016-10

Locations

US (1)