Ovarian Cancer
Conditions
Keywords
chemotherapy, combination therapy, targeted therapy, second-line
Brief 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.
Detailed 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)
Interventions
DRUGTopotecan
DRUGErlotinib
Sponsors
OSI Pharmaceuticals
NYU Langone Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CA125 Response Rate With Continuous-infusion Topotecan and Erlotinib | Up to 3 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CA125 Response Duration | Up to 3 years | 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. |
| CA125 Stable Disease Duration | Up to 3 years | 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. |
| Time to Progression | Up to 3 years | 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. |
| Overall Survival | 4 years | estimated total time from the start of the trial |
| Toxicity Profile | the whole treatment phase and 30 days post-treatment | 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. |
Countries
United States
Participant flow
Recruitment details
From Oct 2009 to May 2011, 6 patients were enrolled to this trial from New York University Medical Center and its affiliated hospitals.
Participants by arm
| Arm | Count |
|---|---|
| Topotecan and Erlotinib On Day 1 of each treatment cycle, topotecan 0.4 mg/m\^2/day was administered via continuous infusion for 9 days beginning on Day 1, every 21 days cycle. Plus erlotinib 150 mg daily for 9 days every 21 days cycle. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Topotecan and Erlotinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 65 years |
| Prior regimens 4 regimens | 1 participants |
| Prior regimens 5 regimens | 3 participants |
| Prior regimens 7 regimens | 1 participants |
| Prior regimens 8 regimens | 1 participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 1 / 6 |
Outcome results
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.
Time frame: Up to 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Topotecan and Erlotinib | CA125 Response Rate With Continuous-infusion Topotecan and Erlotinib | 1 participants |
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.
Time frame: Up to 3 years
Population: The study was terminated very early (6 enrolled vs. 30 target accrual). No statistical analysis was performed on patient data.
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.
Time frame: Up to 3 years
Population: The study was terminated very early (6 enrolled vs. 30 target accrual). No statistical analysis was performed on patient data.
Secondary
Overall Survival
estimated total time from the start of the trial
Time frame: 4 years
Population: The study was terminated very early (6 enrolled vs. 30 target accrual). No statistical analysis was performed on patient data.
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.
Time frame: Up to 3 years
Population: The study was terminated very early (6 enrolled vs. 30 target accrual). No statistical analysis was performed on patient data.
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.
Time frame: the whole treatment phase and 30 days post-treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Topotecan and Erlotinib | Toxicity Profile | Dry skin (grade 1) | 2 participants |
| Topotecan and Erlotinib | Toxicity Profile | Dry skin (grade 3) | 1 participants |
| Topotecan and Erlotinib | Toxicity Profile | Dry eye (grade 1) | 1 participants |
| Topotecan and Erlotinib | Toxicity Profile | Acne (grade 1) | 2 participants |
| Topotecan and Erlotinib | Toxicity Profile | Erythema (grade 1) | 1 participants |
| Topotecan and Erlotinib | Toxicity Profile | Rash/ desquamation (grade 1) | 1 participants |
| Topotecan and Erlotinib | Toxicity Profile | Rash/ desquamation (grade 2) | 1 participants |
| Topotecan and Erlotinib | Toxicity Profile | Pruritis (grade 1) | 1 participants |
| Topotecan and Erlotinib | Toxicity Profile | Diarrhea (grade 1) | 2 participants |
| Topotecan and Erlotinib | Toxicity Profile | Diarrhea (grade 2) | 1 participants |
| Topotecan and Erlotinib | Toxicity Profile | Dehydration (grade 3) | 1 participants |
| Topotecan and Erlotinib | Toxicity Profile | Anemia (grade 2) | 2 participants |
| Topotecan and Erlotinib | Toxicity Profile | Anemia (grade 3) | 2 participants |
| Topotecan and Erlotinib | Toxicity Profile | Leukopenia (grade 2) | 3 participants |
| Topotecan and Erlotinib | Toxicity Profile | Leukopenia (grade 3) | 1 participants |
| Topotecan and Erlotinib | Toxicity Profile | Nausea (grade 2) | 1 participants |
| Topotecan and Erlotinib | Toxicity Profile | Nausea (grade 3) | 1 participants |
| Topotecan and Erlotinib | Toxicity Profile | Vomiting (grade 1) | 3 participants |
| Topotecan and Erlotinib | Toxicity Profile | Vomiting (grade 2) | 1 participants |
| Topotecan and Erlotinib | Toxicity Profile | Vomiting (grade 3) | 1 participants |
| Topotecan and Erlotinib | Toxicity Profile | Platelets (grade 1) | 2 participants |
| Topotecan and Erlotinib | Toxicity Profile | Platelets (grade 2) | 1 participants |
| Topotecan and Erlotinib | Toxicity Profile | Platelets (grade 3) | 1 participants |
| Topotecan and Erlotinib | Toxicity Profile | Fatigue (grade 1) | 2 participants |
| Topotecan and Erlotinib | Toxicity Profile | Fatigue (grade 2) | 1 participants |
| Topotecan and Erlotinib | Toxicity Profile | Fatigue (grade 3) | 1 participants |
| Topotecan and Erlotinib | Toxicity Profile | Nausea (grade 1) | 4 participants |