Ovarian Cancer, Primary Peritoneal Cancer
Conditions
Keywords
ovarian, cancer, peritoneal, endometrioid, mucinous, serous, clear cell
Brief summary
This study will evaluate the efficacy and tolerability of the combination of Gleevec and Gemzar in patients with ovarian cancer, who have progressed after receiving at least one prior chemotherapy treatment. Gleevec is an oral chemotherapy drug used is this study and Gemzar is an IV chemotherapy drug used. Participation in the treatment portion of the study will continue as long as the patient's tumors shrink or remain stable and as long as the patient is able to tolerate the study drug. The follow-up portion of the study will last for 5 years.
Detailed description
Each 21 day period will be considered a cycle. Disease status will be assessed with a Cancer Antigen (CA)-125 prior to the start of each new cycle with an assessment of measurable diseased by either CT or MRI every 6 weeks. Treatment will continue until disease progression, unacceptable toxicities, or the patient elects to withdraw from the study. All patients will be followed until disease progression or study withdraw. In addition, following disease progression, patients will be monitored for delayed toxicity and survival for a period of 5 years, unless consent is withdrawn.
Interventions
DRUGimatinib mesylate by mouth
imatinib mesylate - 400mg orally, daily on Days 1-5 and 8-12 of a 21 day cycle.
DRUGGemcitabine Intravenous
Gemcitabine - 1000 mg/m2 IV on Day 3 and Day 10 of a 21 day cycle
Sponsors
Novartis
Henry M. Jackson Foundation for the Advancement of Military Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients 18 years of age or greater * Histologically documented diagnosis of ovarian cancer or primary peritoneal cancer. Histological subtypes include: mucinous tumor, serous tumor, endometrioid tumor, and other histologies including clear cell and undifferentiated epithelial tumors. * At least one measurable site of disease (as defined by Southwestern Oncology Group Solid Tumor Response Criteria) or other response assessment criteria, as appropriate. * Patients must have relapsed after receiving at least one prior platinum-based chemotherapy. * Performance status of 0, 1, 2, (ECOG) * Adequate end organ function: Total bilirubin \< 1.5 x ULN, SGOT and SGPT \< 2.5 UNL, creatinine \< 1.5 x UNL, ANC \> 1.5 x 109/L, platelets \> 100 x 109/L. * Patients will most likely have had their ovaries removed at the time off initial surgery. If any subjects are of childbearing potential at the time of entry, they must have negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Subjects of reproductive potential must agree to employ and effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of the study drug. * Written, voluntary informed consent. * Patients must be eligible for care at a military medical treatment facility.
Exclusion criteria
* Patient has received prior treatment with Gemzar. * Patient has received any other investigational agents within 28 days of the first day of study drug dosing. * Patient is \< 5 years free of another primary malignancy except: if the other primary malignancy is neither currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed. * Patient with Grade III/IV cardiac problems as defined but the New York Heart Association Criteria. * Patients who are pregnant or breast-feeding. * Patient has a severe and/or uncontrolled medical disease (i,e. uncontrolled diabetes, uncontrolled chronic renal disease, or active uncontrolled infection). * Patient has a known untreated or progressive brain metastasis. * Patient has known chronic liver diseases (i.e. chronic active hepatitis, and cirrhosis. * Patient has a known diagnosis of human immunodeficiency virus (HIV infection ). * Patient received chemotherapy within 4 weeks (6 weeks for nitrosourea or mitomycin-C) prior to study entry, unless the disease is rapidly progressing.. * Patient previously received radiotherapy to greater than or equal to 25% of the bone marrow. * Patient had a major surgery within 2 weeks prior to study entry. * Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Cystostatic, Anti-tumor Activity of the Combination of Gleevec and Gemzar Via Progression-free Survival for at Least Six Months in Patients With Recurrent or Persistent Epithelial Ovarian or Primary Peritoneal Carcinoma. | Time to progression was measured from enrollment in study until documented disease progression over a period not greater than 2 years. | Progression free survival at six months was assessed for all research subjects. Progression defined by SWOG criteria: Invest New Drugs. 1992 Nov;10(4):239-53. Progression is defined as \> 50% increase in the sume of measured cross sectional area of areasa of measurable disease, measured from the lowest measured amount of disease. Progression is also defined as new areas of measurabe disease. |
| To Determine the Safety and Tolerability Via Frequency and Severity of Adverse Effect of Combination Gleevec and Gemzar in This Cohort of Patients as Assessed Byt Common Toxicity Criteria | Until disease progression or unacceptable toxicity | Toxicity was assess prior to each cycle of therapy (every 3 weeks) and graded based on NCI common toxicity criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response Rates Using Modified SWOG Criteria to the Combination of Gleevec and Gemzar in Patients With Relapsed Ovarian Cancer Who Have Failed at Least One Prior Chemotherapy Treatment. | Subjects treated until progression of disease or unacceptable toxicity. no maximum dose was specified | Best response to thearpy was assessed using modified SWOG criteria (same as for outcome masure #1). Subjects were assess as complete response, partial response, stable disease, and progressive disease after 2 cycles (6 weeks) of beginning treatment and every 6 weeks afterward until progression of disease, unacceptable toxicity, or subject withdrawl from study. the measurement reported is the number of patients who met the criteria for partial response. |
| To Determine the Distribution of the Overall Survival | Until death | All subjects were followed after treatment was complete to assess overall survival. |
| To Estimate the Clinical Response Rate(Partial and Complete Response as Defined Under the SWOG Criterial) | until disease progression or unacceptable toxicity | Using SWOG criteria for response of measurable disease, subject best response was assessed. First assessment was 6 weeks after starting treatment. Subjequent evaluations were every 6 weeks in patients who remained on study. Repsonse rate was the sum of Complete Repsonse and Partial Response. |
| To Assess the Effects of Prognostic Variables; Initial Performance Status; Platinum Sensitivity, and Mucinous (or Clear Cell)Histology on Progression-free Survival Overall. | Until disease progression | The study was stopped after 8 subjects. It was not possible to perform meaningful analysis on prognostic variables. this outcome measure was not done. |
Countries
United States
Participant flow
Recruitment details
Three subjects were enrolled at Brooke Army Medical Center. Five subjects were enrolled at Madigan Army Medical Center. Seven of eght subjects are deceased as of 4/4/2013.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Open label, non-randomized, single treatment group. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age, Continuous | 61.5 years STANDARD_DEVIATION 7.3 |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 8 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 | 0 / 8 |
| serious Total, serious adverse events | 3 / 8 |
Outcome results
Primary
The Cystostatic, Anti-tumor Activity of the Combination of Gleevec and Gemzar Via Progression-free Survival for at Least Six Months in Patients With Recurrent or Persistent Epithelial Ovarian or Primary Peritoneal Carcinoma.
Progression free survival at six months was assessed for all research subjects. Progression defined by SWOG criteria: Invest New Drugs. 1992 Nov;10(4):239-53. Progression is defined as \> 50% increase in the sume of measured cross sectional area of areasa of measurable disease, measured from the lowest measured amount of disease. Progression is also defined as new areas of measurabe disease.
Time frame: Time to progression was measured from enrollment in study until documented disease progression over a period not greater than 2 years.
Population: of 8 enrolled subjects, 7 were eligible for analysis of progression-free survival at 8 months. One subject declined to continue treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Imatinib Plus Gemcitabine | The Cystostatic, Anti-tumor Activity of the Combination of Gleevec and Gemzar Via Progression-free Survival for at Least Six Months in Patients With Recurrent or Persistent Epithelial Ovarian or Primary Peritoneal Carcinoma. | 0 participants |
Primary
To Determine the Safety and Tolerability Via Frequency and Severity of Adverse Effect of Combination Gleevec and Gemzar in This Cohort of Patients as Assessed Byt Common Toxicity Criteria
Toxicity was assess prior to each cycle of therapy (every 3 weeks) and graded based on NCI common toxicity criteria
Time frame: Until disease progression or unacceptable toxicity
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oral Imatinib Plus Gemcitabine | To Determine the Safety and Tolerability Via Frequency and Severity of Adverse Effect of Combination Gleevec and Gemzar in This Cohort of Patients as Assessed Byt Common Toxicity Criteria | Grade 3 toxicity | 3 participants |
| Oral Imatinib Plus Gemcitabine | To Determine the Safety and Tolerability Via Frequency and Severity of Adverse Effect of Combination Gleevec and Gemzar in This Cohort of Patients as Assessed Byt Common Toxicity Criteria | Grade 4 toxicity | 1 participants |
| Oral Imatinib Plus Gemcitabine | To Determine the Safety and Tolerability Via Frequency and Severity of Adverse Effect of Combination Gleevec and Gemzar in This Cohort of Patients as Assessed Byt Common Toxicity Criteria | Red Blood Cell Transfusion | 1 participants |
Secondary
To Assess the Effects of Prognostic Variables; Initial Performance Status; Platinum Sensitivity, and Mucinous (or Clear Cell)Histology on Progression-free Survival Overall.
The study was stopped after 8 subjects. It was not possible to perform meaningful analysis on prognostic variables. this outcome measure was not done.
Time frame: Until disease progression
Secondary
To Determine the Distribution of the Overall Survival
All subjects were followed after treatment was complete to assess overall survival.
Time frame: Until death
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oral Imatinib Plus Gemcitabine | To Determine the Distribution of the Overall Survival | 9 months |
Secondary
To Estimate the Clinical Response Rate(Partial and Complete Response as Defined Under the SWOG Criterial)
Using SWOG criteria for response of measurable disease, subject best response was assessed. First assessment was 6 weeks after starting treatment. Subjequent evaluations were every 6 weeks in patients who remained on study. Repsonse rate was the sum of Complete Repsonse and Partial Response.
Time frame: until disease progression or unacceptable toxicity
Population: All subjects were assessed after 6 weeks of treatment and reassessed at 6 week intervals
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Imatinib Plus Gemcitabine | To Estimate the Clinical Response Rate(Partial and Complete Response as Defined Under the SWOG Criterial) | 0 participants |
Secondary
Tumor Response Rates Using Modified SWOG Criteria to the Combination of Gleevec and Gemzar in Patients With Relapsed Ovarian Cancer Who Have Failed at Least One Prior Chemotherapy Treatment.
Best response to thearpy was assessed using modified SWOG criteria (same as for outcome masure #1). Subjects were assess as complete response, partial response, stable disease, and progressive disease after 2 cycles (6 weeks) of beginning treatment and every 6 weeks afterward until progression of disease, unacceptable toxicity, or subject withdrawl from study. the measurement reported is the number of patients who met the criteria for partial response.
Time frame: Subjects treated until progression of disease or unacceptable toxicity. no maximum dose was specified
Population: All subjects who underwent treatment and participated in the study were analysed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Imatinib Plus Gemcitabine | Tumor Response Rates Using Modified SWOG Criteria to the Combination of Gleevec and Gemzar in Patients With Relapsed Ovarian Cancer Who Have Failed at Least One Prior Chemotherapy Treatment. | 0 participants |