Topotecan With Erlotinib for Topotecan Pretreated Ovarian Cancer

Ovarian Cancer Clinical Trial

Official title:

Continuous Infusion Topotecan With Erlotinib for Topotecan Pretreated Ovarian Cancer: Tumor Features and Phase II/Pharmacokinetic Evaluation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01003938
• Other study ID #: NYU 08-613
• Status: Terminated
• Phase: Phase 2
• First received: October 27, 2009
• Last updated: December 2, 2013
• Start date: August 2009
• Est. completion date: December 2012

Study information

• Verified date: December 2013
• Source: New York University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a single arm phase II study with a combination of Hycamptin® (topotecan) and erlotinib for a minimum of 2 cycles in patients (18 yrs of age and older) with recurrent ovarian cancer previously treated with chemotherapy drug Hycamptin® (topotecan). Up to 30 patients will be enrolled in this study.

Description:

On Day 1 of each treatment cycle, topotecan 0.4 mg/m^2/day will be administered via continuous infusion for 9 days beginning on Day 1 of every 21 day cycle. Additionally, patients will receive erlotinib 150 mg daily Days 1-9 in a cycle of 21 days. Thereafter both drugs will be given as long as patient benefit continues. Treatment will be administered on an inpatient or outpatient basis, repeating administration on an every 3 week cycle.

A cycle will be one three-week course of the erlotinib-topotecan regimen (the cycle could be extended to 4 weeks if blood studies at 21 days result in treatment delay).

The dose of topotecan will be calculated as follows:

BSA (m^2) X drug dose (mg/m^2) = dose (mg)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: December 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologically or cytologically proven, previously treated, epithelial ovarian cancer, and/or serous ovarian cancer.

2. Evaluable disease with CA125 levels two times the upper limit of normal for the institution (>50u/ml ) on two occasions at least one week apart is required in order to apply CA-125 response criteria.

3. Previously treated for ovarian cancer with a taxane and platinum based regimen. and an additional topotecan regimen (any number of chemotherapy or biologic therapies are allowed; including prior erlotinib are allowed)

4. Age >= 18 years.

5. Minimum life expectancy: 4 months.

6. ECOG (Eastern Cooperative Oncology Group) performance status 0,1, or 2. 0: Fully active, unrestricted activities of daily living. 1: Ambulatory, but restricted in strenuous activity. 2: Ambulatory, and capable of self care. Unable to work. Out of bed for greater than 50% of waking hours.

7. Complete blood count (CBC) performed less than seven days prior to enrollment and have an absolute neutrophil count >1.0 X 10^9/L, and a platelet count >100 X 10^9/L.

8. Serum chemistry panel drawn less than seven days prior to enrollment and have a total bilirubin <= 1.5 X the institutional upper limit of normal (IULN), or SGOT/AST is < 2.5 X IULN.

9. Serum creatinine <= 1.5 X institutional upper limit of normal (IULN). If the serum creatinine level is >= 1.5 IULN, but the serum creatinine clearance >= 50 mg/dL, then the subject can enter the study.

10. Central line access.

11. Signed written informed consent (approved by the Institutional Review Board [IRB]/Ethics Committee) obtained prior to study entry.

Exclusion Criteria:

If the answer to any of the exclusion criteria is YES, the subject is NOT ELIGIBLE for the study.

1. Presence of active cancer other than that described in Section 3.1.criteria (a), with the exception of a diagnosis of synchronous occurrence of adenocarcinoma in ovary and uterus.

2. Uncontrolled intercurrent illness not limited to infection, symptomatic congestive heart failure, or unstable angina pectoris, or cardiac arrhythmia.

3. Acute toxicity of prior chemotherapy is still present

4. History of severe allergic reaction to erlotinib

5. Unresolved sequelae resulting from any surgical procedures.

6. Symptomatic, untreated brain metastases. Patients with untreated brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

7. Lactating or pregnant. The investigational agent topotecan may be toxic to the developing fetus or nursing infant and poses unknown health risks. Documentation of a negative, serum HCG pregnancy test is required for women of child bearing potential (WOCBP) within 2 weeks prior to the start of treatment. WOCBP is defined as women who have not been naturally postmenopausal for at least 12 consecutive months or no previous surgical sterilization. A negative pregnancy test within 2 weeks prior to start of treatment is required.

8. Women of childbearing potential must use effective contraception throughout the time they are on study. Before entering this trial, patients must be made aware of the risk in becoming pregnant.

9. Receipt of any investigational drug within 28 days before beginning treatment with study drug and/or concomitant treatment with other investigational agents.

10. Patients with a history of poorly controlled gastrointestinal disorders that could affect absorption of erlotinib (e.g. Crohn's, ulcerative colitis, etc)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Topotecan

• Erlotinib

Locations

Country	Name	City	State
United States	Bellevue Hospital Center	New York	New York
United States	NYU Clinical Cancer Center	New York	New York
United States	Tisch Hospital	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
New York University School of Medicine	OSI Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CA125 Response Rate With Continuous-infusion Topotecan and Erlotinib	Response was assessed after every treatment cycle. Response rate is defined as number of the patients who experienced complete or partial CA125 response (CR or PR). CR: normalization of the CA125 value, determined by 2 observations not less than 4 weeks apart; PR: CA125 decreases by >50% and is confirmed to be 50% or greater on a subsequent determination at least one month later.	Up to 3 years	No
Secondary	CA125 Response Duration	Response duration is measured from the time measurement criteria for CA125 CR/PR at the first met until the first date that recurrent or progressive disease is objectively documented.	Up to 3 years	No
Secondary	CA125 Stable Disease Duration	Stable disease (SD) duration is measured from the tile of start of therapy until the criteria for progression are met. SD: CA125 decreases <50% or increases <100%. Disease progression: CA125 doubles the value of baseline, or more, over time.	Up to 3 years	No
Secondary	Time to Progression	Time to progression is defined as the time from first study drug administration until the first day radiological and /or symptomatic disease progression is documented, or until death in the absence of progression.	Up to 3 years	No
Secondary	Overall Survival	estimated total time from the start of the trial	4 years	No
Secondary	Toxicity Profile	Number of participants (patients) who experienced AEs.; Dry skin, dry eye, acne, erythema, rash, pruritus, and diarrhea were related erlotinib; dehydration, anemia, leukopenia, nausea, vomiting, platelets, and fatigue were realted to topotcan.	the whole treatment phase and 30 days post-treatment	Yes