Phase I Trial of Oral Metronomic Topotecan and Oral Pazopanib to Treat Recurrent/Persistent Gynecologic Tumors

NCT00800345 | Completed Phase 1 Results

• 1 other identifier: ATDTRPST0802
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, dose-escalation study in female patients with recurrent or persistent gynecologic tumors.

Conditions

Gynecologic Tumors

Keywords

Gynecologic tumors

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity (DLT)

  Cycle 1 (28 days)

Secondary Outcomes (1)

• Treatment Response

  After every 2 cycles of treatment beginning on Cycle 1 Day 1, up to 38 months

Study Arms (1)

Experimenal

EXPERIMENTAL

Metronomic oral topotecan and oral pazopanib will be administered by mouth beginning on Cycle 1 Day 1. Patients will be enrolled and observed for dose limiting toxicity (DLT) for 1 cycle of treatment. Dose modification of the combination will depend on the number of patients experiencing DLT(s) at each dose level.

Drug: Oral Topotecan; Drug: Pazopanib

Interventions

Oral Topotecan DRUG

Starting on Cycle 1 Day 1, each subject will receive the assigned dose of topotecan administered by mouth.

Also known as: Hycamtin capsules

Experimenal

Pazopanib DRUG

Starting on Cycle 1 Day 1, each subject will receive the assigned dose of pazopanib administered by mouth.

Also known as: GW786034, Votrient

Experimenal

Eligibility Criteria

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

You may qualify if:

• Subjects must provide written informed consent prior to the performance of study specific procedures, and must be willing to comply with treatment and follow-up.
• Female patients, greater than 18 years of age with a histologically confirmed recurrent/persistent gynecologic malignancy.
• For patients with recurrent/persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma: persistent disease = progression during primary platinum therapy; recurrent disease = disease that recurs ≤ 12 months after discontinuing primary platinum therapy; if disease recurrence occurs \> 12 months after discontinuing primary platinum therapy, there must be progression either during a 2nd platinum therapy or \< 6 months after discontinuing the 2nd platinum therapy.
• For patients with other gynecologic malignancies:
• Malignancy is metastatic or unresectable and no curative or palliative measures exist or are no longer effective.
• Maximum of two total prior treatments (this includes neoadjuvant, adjuvant, and metastatic settings) for the recurrent or persistent gynecologic tumors including chemotherapy, hormonal therapy, investigational therapy, radiation therapy, etc.)
• Disease may be measurable or non-measurable according to RECIST version 1.0
• Gynecologic Oncology Group (GOG) performance status of 0,1,or 2
• Must have a life expectancy of at least six months
• Adequate bone marrow, liver, renal, and cardiac function at study entry as assessed by the following:
• Hemoglobin \> 9.0 g/dL.
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L.
• Platelet count ≥ 100 x 10\^9/L.
• Prothrombin time (PT) or international normalized ratio (INR) \< 1.2 x upper limit of normal (ULN).
• Partial thromboplastin time (PTT) \< 1.2 x ULN.

You may not qualify if:

• Treatment naive patients.
• Repetitive or prolonged neutropenia or thrombocytopenia during previous therapy.
• Concurrent malignancy other than malignancies under study. Subjects who have had another malignancy and have been disease free for 3 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
• Prior radiation therapy.
• Myelosuppressive chemotherapy within the past 28 days or has not recovered from the myelosuppressive effects of recent chemotherapy.
• Use of an investigational agent, including an investigational anti-cancer agent, immunotherapy, biological therapy, or hormonal therapy within 28 days prior to the first dose of study treatment.
• Prior major surgery or trauma within 28 days prior to the first dose of study treatment and/or presence of any non-healing wound, fracture, or ulcer.
• History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis.
• Inability to swallow a capsule or clinically significant gastrointestinal abnormalities including, but not limited to:
• Malabsorption syndrome
• Major resection of the stomach or small bowel that could affect the absorption of study treatment
• Active peptic ulcer disease
• Inflammatory bowel disease
• Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment.

Sponsors & Collaborators

• Vector Oncology: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

The West Clinic

Memphis, Tennessee, 38120, United States

Location

MeSH Terms

Interventions

Topotecan; pazopanib

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Vice President of Scientific Affairs
• Organization: Vector Oncology

mwalker@vectoroncology.com

901.435.5570

Study Officials

• Todd D Tillmanns, MD

  The West Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• 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: December 1, 2008
• First Posted: December 2, 2008
• Study Start: April 1, 2009
• Primary Completion: June 1, 2015
• Study Completion: September 1, 2015
• Last Updated: March 28, 2017
• Results First Posted: February 23, 2017

Record last verified: 2016-12

Locations

US (1)