Sorafenib + Topotecan for Platinum-Resistant Recurrent Ovarian Cancer

NCT00526799 | Terminated Phase 1 Results DMC

• 1 other identifier: GYN06-111
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 8

Brief Summary

This multi-institutional phase I/II clinical trial will test the tolerability and efficacy of the combination sorafenib and topotecan in patients with recurrent ovarian cancer, which is platinum-resistant (recurrence within 6 months from completing platinum based therapy) or refractory (progressive disease during platinum based therapy).

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  An initial 3 patients will be enrolled at dose level 1. If all 3 patients in dose level 1 complete the first cycle of therapy without a dose limiting toxicity (DLT), 3 patients will be enrolled at dose level 2. If 0 of 3 or 1 of 6 patients in dose level 2 experience a DLT, all subsequent patients will be enrolled in the Phase II cohort at dose level 2. If 2 of the first 3 or 2 of the total 6 patients experience DLT at dose level 2, then dose level 1 will be considered the MTD and used in the second phase.

  Each participant was treated at their assigned dose level on 28 day cycles until disease progression or unacceptable toxicity. Participants were evaluated for toxicity every two weeks.

• Percentage of Participants With Response

  To assess response in patients with recurrent or resistant epithelial ovarian cancer treated with Sorafenib plus Topotecan. Reponse evaluated per RECIST criteria where: Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started

  Disease assessments were conducted on the 8th week (Cycle 2, Week 4) and every eight weeks there after, until treatment discontinuation

Secondary Outcomes (3)

• Progression-free Survival

  From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely

• Clinical Benefit

  From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely

• Duration of Stable Disease

  From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely

Study Arms (2)

Phase I

EXPERIMENTAL

Topotecan 3.5 mg/m\^2 + Sorafenib dose escalation:

Drug: Sorafenib; Drug: Topotecan

Phase II

EXPERIMENTAL

Topotecan 3.5 mg/m\^2 + Sorafenib 400 mg po daily.

Drug: Sorafenib; Drug: Topotecan

Interventions

Sorafenib DRUG

Phase I: Dose Escalation, Phase II: MTD Dose level -1: 200mg po daily Dose level 1: 400mg po daily (MTD) Dose level 2: 400mg po bid

Phase I; Phase II

Topotecan DRUG

3.5mg/m2 weekly, 3 weeks on and one week off.

Phase I; Phase II

Eligibility Criteria

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

You may qualify if:

• Have histologically-confirmed epithelial ovarian cancer, primary peritoneal carcinomatosis or fallopian tube cancer. Enrollment of patients with clear cell histology is encouraged.
• Have measurable disease according to RECIST or detectable disease by 1) CA-125 at least twice the ULN within 14 days prior to registration for protocol therapy; 2) Ascites and/or pleural effusion attributed to tumor; 3) solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST definitions for target lesions.
• Have failed at least one prior platinum based chemotherapeutic regimen.
• No more than 3 prior treatment regimens for epithelial ovarian cancer.
• Prior radiation therapy is allowed to \< 25% of the bone marrow.
• Be at least 4 weeks since last anti-cancer treatment, radiation or surgery at the time of registration for protocol therapy.
• No active cancer in addition to the epithelial ovarian cancer within the last 5 years, with the exception of: superficial skin cancer (basal cell or squamous cell skin carcinoma; carcinoma in situ of the cervix; Stage I endometrial cancer with less than 50% invasion of the myometrium, or other adequately treated Stage I or II cancer in complete remission.
• Age \> 18 years at the time of consent
• Written informed consent and HIPAA authorization for release of personal health information.
• Females of childbearing potential must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 90 days after treatment discontinuation
• Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy.

You may not qualify if:

• No known or suspected allergy to sorafenib or any agent given in the course of this trial.
• No prior treatment with anti-angiogenesis therapy.
• No active CNS metastases.
• No treatment with any investigational agent within 30 days prior to being registered for protocol therapy.
• No concurrent combination anti-retroviral therapy for the treatment of immunodeficiency.
• No clinically significant infections requiring antibiotic treatment.
• No evidence of bowel obstruction, malabsorption, or other contraindication to oral medication.
• No serious non-healing wound, ulcer, or bone fracture.
• No major surgery, open biopsy or significant traumatic injury within 28 days of registration for protocol therapy.
• No use of St. John's Wort or rifampin (rifampicin) while on protocol therapy.
• No condition that impairs patient's ability to swallow whole pills.

Sponsors & Collaborators

• Daniela Matei, MD: lead
• Bayer: collaborator
• Hoosier Cancer Research Network: collaborator

Study Sites (8)

Medical & Surgical Specialists, LLC

Galesburg, Illinois, 61401, United States

Location

Oncology Hematology Associates of SW Indiana

Evansville, Indiana, 47714, United States

Location

Fort Wayne Oncology & Hematology, Inc

Fort Wayne, Indiana, 46815, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

St. Vincent Hospital Cynecologic Oncology

Indianapolis, Indiana, 46260, United States

Location

Arnett Cancer Care

Lafayette, Indiana, 47904, United States

Location

Medical Consultants, P.C.

Muncie, Indiana, 47303, United States

Location

Schwartz Gynecologic Oncology, PLLC

Brightwaters, New York, 11718, United States

Location

Related Publications (1)

• Matei D, Emerson RE, Schilder J, Menning N, Baldridge LA, Johnson CS, Breen T, McClean J, Stephens D, Whalen C, Sutton G. Imatinib mesylate in combination with docetaxel for the treatment of patients with advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis : a Hoosier Oncology Group trial. Cancer. 2008 Aug 15;113(4):723-32. doi: 10.1002/cncr.23605.

  PMID: 18618737 BACKGROUND

Related Links

• Hoosier Cancer Research Network Homepage

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Sorafenib; Topotecan

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)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Camptothecin; Alkaloids

Results Point of Contact

• Title: Principal Investigator
• Organization: Hoosier Cancer Research Network, Inc.

jsmith@hoosiercancer.org

317-921-2050

Study Officials

• Daniela Matei, M.D.

  Hoosier Oncology Group, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: September 5, 2007
• First Posted: September 10, 2007
• Study Start: September 1, 2007
• Primary Completion: January 1, 2010
• Study Completion: August 1, 2010
• Last Updated: March 3, 2016
• Results First Posted: March 3, 2016

Record last verified: 2016-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)