Oxaliplatin and Topotecan in Advance Ovarian Cancer
Study Details
Study Description
Brief Summary
This phase II trial is studying how well giving oxaliplatin together with topotecan works in treating patients with ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer. Drugs used in chemotherapy, such as oxaliplatin and topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
-
Estimate the overall clinical response rate (complete and partial responses) in patients with previously treated ovarian epithelial, primary peritoneal, or fallopian tube cancer treated with oxaliplatin and topotecan.
-
Determine the toxic effects in patients treated with this regimen.
SECONDARY OBJECTIVES:
- Estimate the time to progression and overall clinical response duration in patients treated with this regimen.
OUTLINE: This is an open-label, multicenter study. Patients are stratified according to response to prior platinum therapy (resistant vs sensitive).
Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and topotecan IV continuously on days 1-14. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 30 days.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (oxaliplatin plus topotecan) Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and topotecan IV continuously on days 1-14. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 30 days. |
Drug: oxaliplatin
Given IV
Other Names:
Drug: topotecan
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Clinical Response Rate (Complete and Partial Response by RECIST and/or CA [Cancer Antigen] 125) [Every two cycles for up to 24 weeks.]
Tumor response was assessed every two cycles by CT/MRI using RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Per Response Evaluation Criteria in Solid Tumors (RECIST 1.0) for target lesions: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >= 30% decrease in the sum of the longest diameter (LD) of target lesions; Overall Response (OR) = CR + PR.
Secondary Outcome Measures
- Time to Disease Progression by RECIST and/or CA 125 [Tumor measurements will be performed every 8 weeks until the date of first documented progression up to 100 weeks]
Time to disease progression by RECIST and/or CA 125
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically or cytologically confirmed ovarian epithelial, primary peritoneal, or fallopian tube cancer
-
Meets 1 of the following criteria for response to prior platinum-based therapy:
-
Platinum-resistant disease, defined as a disease-free interval of < 6 months after prior platinum-based therapy OR progressive disease on a platinum-containing regimen
-
Platinum-sensitive disease, defined as a disease-free interval of > 6 months after prior platinum-based therapy
-
Measurable or evaluable disease: Measurable disease is characterized as lesions reproducibly measurable in 1 dimension; evaluable disease is defined as known disease with CA125 levels > 50 U/mL on 2 occasions >= 1 week apart
-
Previously treated with a taxane and platinum-based regimen, only 1 prior platinum-based regimen, including IV or intraperitoneal consolidation, one additional non-platinum and non-topotecan chemotherapy regimen allowed
-
Life expectancy >= 4 months
-
Total bilirubin =< 1.5 times upper limit of normal (ULN)
-
AST =< 2.5 times ULN (5 times ULN if liver metastases are present)
-
Creatinine =< 1.5 times ULN AND creatinine clearance > 40 mg/dL
Exclusion criteria:
-
No presence of any other active cancer
-
No uncontrolled intercurrent illness, including the following:
-
Infection
-
Symptomatic congestive heart failure
-
Unstable angina pectoris
-
Cardiac arrhythmia
-
No history of severe allergy to platinum compounds
-
(Mild reaction (skin only) allowed provided a negative skin test is obtained)
-
No history of allergic reaction to appropriate antiemetics (e.g., 5HT3 antagonists)
-
Recovered from prior chemotherapy
-
At least 2 weeks since prior radiotherapy and recovered
-
At least 4 weeks since prior investigational drugs
-
No prior radiotherapy to the whole pelvic field
-
No unresolved sequelae resulting from any surgical procedures
-
No concurrent colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) during topotecan infusion
-
No concurrent participation in another investigational trial
-
No other concurrent investigational agents
-
No other concurrent anticancer therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Montefiore Medical Center | Bronx | New York | United States | 10467-2490 |
| 2 | NYU Cancer Institute | New York | New York | United States | 10016 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Amy Tiersten, Montefiore Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2009-00053
- NYU 03-67
- N01CM62204
Study Results
Participant Flow
| Recruitment Details | A total of 39 patients were enrolled from 3 institutions between January 2006 and October 2009 |
|---|---|
| Pre-assignment Detail | 1 patient never received treatment |
| Arm/Group Title | Treatment Stratum I (Oxaliplatin Plus Topotecan) | Treatment Stratum II (Oxaliplatin Plus Topotecan) |
|---|---|---|
| Arm/Group Description | Treatment stratum I (oxaliplatin plus topotecan) is resistant to prior platinum therapy. Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and topotecan IV continuously on days 1-14. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 30 days. oxaliplatin: Given IV topotecan: Given IV | Treatment stratum II (oxaliplatin plus topotecan) is sensitive to prior platinum therapy. Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and topotecan IV continuously on days 1-14. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 30 days. oxaliplatin: Given IV topotecan: Given IV |
| Period Title: Overall Study | ||
| STARTED | 19 | 20 |
| COMPLETED | 19 | 19 |
| NOT COMPLETED | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | Treatment Stratum I: (Oxaliplatin Plus Topotecan) | Treatment Stratum II (Oxaliplatin Plus Topotecan) | Total |
|---|---|---|---|
| Arm/Group Description | Treatment stratum I (oxaliplatin plus topotecan) is resistant to prior platinum therapy. Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and topotecan IV continuously on days 1-14. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 30 days. oxaliplatin: Given IV topotecan: Given IV | Treatment stratum II (oxaliplatin plus topotecan) is sensitive to prior platinum therapy. Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and topotecan IV continuously on days 1-14. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 30 days. oxaliplatin: Given IV topotecan: Given IV | Total of all reporting groups |
| Overall Participants | 19 | 20 | 39 |
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
61
|
59
|
60
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
19
100%
|
20
100%
|
39
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Clinical Response Rate (Complete and Partial Response by RECIST and/or CA [Cancer Antigen] 125) |
|---|---|
| Description | Tumor response was assessed every two cycles by CT/MRI using RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Per Response Evaluation Criteria in Solid Tumors (RECIST 1.0) for target lesions: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >= 30% decrease in the sum of the longest diameter (LD) of target lesions; Overall Response (OR) = CR + PR. |
| Time Frame | Every two cycles for up to 24 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 30 patients were analyzed. Eight patients discontinued treatment before 2 cycles. |
| Arm/Group Title | Treatment Stratum I (Oxaliplatin Plus Topotecan) | Treatment Stratum II (Oxaliplatin Plus Topotecan) |
|---|---|---|
| Arm/Group Description | Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and topotecan IV continuously on days 1-14. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 30 days. oxaliplatin: Given IV topotecan: Given IV | Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and topotecan IV continuously on days 1-14. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 30 days. oxaliplatin: Given IV topotecan: Given IV |
| Measure Participants | 16 | 14 |
| Complete Response |
3
15.8%
|
3
15%
|
| Partial Response |
1
5.3%
|
6
30%
|
| Stable Disease |
8
42.1%
|
4
20%
|
| Disease Progression |
4
21.1%
|
1
5%
|
| Title | Time to Disease Progression by RECIST and/or CA 125 |
|---|---|
| Description | Time to disease progression by RECIST and/or CA 125 |
| Time Frame | Tumor measurements will be performed every 8 weeks until the date of first documented progression up to 100 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment Stratum I (Oxaliplatin Plus Topotecan) | Treatment Stratum II (Oxaliplatin Plus Topotecan) |
|---|---|---|
| Arm/Group Description | Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and topotecan IV continuously on days 1-14. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 30 days. oxaliplatin: Given IV topotecan: Given IV | Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and topotecan IV continuously on days 1-14. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 30 days. oxaliplatin: Given IV topotecan: Given IV |
| Measure Participants | 19 | 19 |
| Median (95% Confidence Interval) [months] |
6.3
|
12.6
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Treatment Stratum I (Oxaliplatin Plus Topotecan) | Treatment Stratum II (Oxaliplatin Plus Topotecan) | ||
| Arm/Group Description | Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and topotecan IV continuously on days 1-14. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 30 days. oxaliplatin: Given IV topotecan: Given IV | Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and topotecan IV continuously on days 1-14. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 30 days. oxaliplatin: Given IV topotecan: Given IV | ||
All Cause Mortality |
||||
| Treatment Stratum I (Oxaliplatin Plus Topotecan) | Treatment Stratum II (Oxaliplatin Plus Topotecan) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Treatment Stratum I (Oxaliplatin Plus Topotecan) | Treatment Stratum II (Oxaliplatin Plus Topotecan) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/19 (73.7%) | 12/19 (63.2%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 4/19 (21.1%) | 4 | 1/19 (5.3%) | 1 |
| RBC transfusion | 4/19 (21.1%) | 4 | 1/19 (5.3%) | 1 |
| Gastrointestinal disorders | ||||
| Diarrhea | 0/19 (0%) | 0 | 1/19 (5.3%) | 1 |
| Constipation | 1/19 (5.3%) | 1 | 1/19 (5.3%) | 1 |
| General disorders | ||||
| Fatigue | 1/19 (5.3%) | 1 | 2/19 (10.5%) | 2 |
| Investigations | ||||
| Neutropenia | 3/19 (15.8%) | 3 | 12/19 (63.2%) | 12 |
| Thrombocytopenia | 5/19 (26.3%) | 5 | 10/19 (52.6%) | 10 |
| Platelet transfusion | 1/19 (5.3%) | 1 | 2/19 (10.5%) | 2 |
| Alanine aminotransferase | 1/19 (5.3%) | 1 | 0/19 (0%) | 0 |
| Aspartate aminotransferase | 1/19 (5.3%) | 1 | 0/19 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Treatment Stratum I (Oxaliplatin Plus Topotecan) | Treatment Stratum II (Oxaliplatin Plus Topotecan) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 18/19 (94.7%) | 18/19 (94.7%) | ||
| Gastrointestinal disorders | ||||
| Vomiting | 4/19 (21.1%) | 4 | 4/19 (21.1%) | 4 |
| Nausea | 9/19 (47.4%) | 9 | 18/19 (94.7%) | 18 |
| Mucositis oral | 0/19 (0%) | 0 | 3/19 (15.8%) | 3 |
| Abdominal pain | 4/19 (21.1%) | 4 | 5/19 (26.3%) | 5 |
| Investigations | ||||
| Weight loss | 3/19 (15.8%) | 3 | 0/19 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Anorexia | 10/19 (52.6%) | 10 | 7/19 (36.8%) | 7 |
| Nervous system disorders | ||||
| Peripheral sensory neuropathy | 9/19 (47.4%) | 9 | 16/19 (84.2%) | 16 |
| Headache | 0/19 (0%) | 0 | 5/19 (26.3%) | 5 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnea | 3/19 (15.8%) | 3 | 5/19 (26.3%) | 5 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 0/19 (0%) | 0 | 3/19 (15.8%) | 3 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Lisa Escobar-Peralta |
|---|---|
| Organization | Montefiore Medical Center |
| Phone | 718-379-6866 |
| lescobar@montefiore.org |
- NCI-2009-00053
- NYU 03-67
- N01CM62204