Carboplatin, Paclitaxel, and Surgery in Treating Patients With Advanced Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer

• Sponsor: Masonic Cancer Center, University of Minnesota (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00331422
• Collaborator: (none)
• Enrollment: 7
• Location: 1
• Arm: 1
• Duration (Months): 41
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or stopping them from dividing. Giving chemotherapy drugs before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well giving paclitaxel together with carboplatin before surgery works in treating patients with advanced ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cavity cancer.

Condition or Disease	Intervention/Treatment	Phase
Fallopian Tube Cancer; Ovarian Cancer; Peritoneal Cavity Cancer	Drug: carboplatin; Drug: paclitaxel; Procedure: cytoreductive surgery	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine whether at least 50% of patients with advanced ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer are able to achieve optimal cytoreduction (to < 1 centimeter of remaining disease) after neoadjuvant chemotherapy comprising paclitaxel and carboplatin.

Secondary

• Determine the frequency and severity of toxicity associated with this regimen in patients who are high-risk surgical candidates or in patients unlikely to achieve optimal surgical cytoreduction.

• Determine if extreme drug resistance assay profiles change after neoadjuvant chemotherapy.

• Determine how thrombospondin-1 (TSP-1), tumor protein 53 (p53), and tumor vessel density change after administration of neoadjuvant chemotherapy.

• Assess the quality of life of patients receiving neoadjuvant chemotherapy.

• Obtain estimates of tumor response after administration of neoadjuvant chemotherapy.

• Determine whether serum cancer antigen 125 (CA-125) at the time of cytoreduction is associated with the ability to optimally reduce the patients.

OUTLINE: This is an open-label study.

Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Within 4-6 weeks after the fourth course of chemotherapy, patients undergo interval cytoreductive surgery.

Patients who are unable to undergo surgery receive 2 additional courses of chemotherapy and are re-evaluated for surgery after the sixth course of chemotherapy.

Within 4 weeks after surgery, patients receive 2 additional courses of chemotherapy.

Quality of life is assessed periodically.

Tumor samples are obtained via laparoscopic or percutaneous biopsy prior to beginning chemotherapy and during interval cytoreduction. Tissue is examined by immunohistochemistry staining for p53, TSP-1, microvessel density (CD31), angiogenesis, membrane protein BCL-2, and multidrug resistant gene 1 (MDR-1). Gene array analysis and extreme drug resistant assays are also performed.

After completion of study treatment, patients are followed every 3 months for 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Carboplatin and Paclitaxel as Neoadjuvant Chemotherapy Followed by Interval Cytoreduction in Women With Advanced Staged Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma for High-Risk Surgical Candidates or Patients Unlikely to be Optimally Surgically Cytoreduced
• Study Start Date: Oct 1, 2005
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Patients Who Received Treatment All patients receiving treatment with Paclitaxel and Carboplatin followed by surgery to remove cancerous tissue.

Drug: carboplatin; Carboplatin dose (milligrams (mg)) - Target Area Under the Curve (AUC) 6 x (Glomerular Filtration Rate+25) - Calvert Formula, given intravenously (IV) for 30 minutes.; Other Names: Paraplatin ; Drug: paclitaxel; Paclitaxel dose = 175 milligrams per meter squared (mg/m2) over 3 hours.; Other Names: Taxol ; Procedure: cytoreductive surgery; Surgery - tumor specimen collected for extreme drug resistant assay (EDR) and A1 assays for analysis; Other Names: surgery debulking

Outcome Measures

Primary Outcome Measures

1. Number of Patients Who Underwent Optimal Cytoreduction After Chemotherapy [Week 18 (After 4 cycles of chemotherapy)]

   These patients had their tumor(s) removed by surgery after receiving 4 cycles of chemotherapy to determine their response.

Secondary Outcome Measures

1. Patients' Overall Tumor Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) [Week 16 (4 weeks after 4th course)]

   Best response recorded from start of treatment until after 4th cycle of treatment. Defined by the sum of Complete Responses (CR), Partial Responses (PR), and Stable Disease (SD) in patients neoadjuvant chemotherapy. CR=disappearance of all lesions, PR=>or=30% decrease in sumof all target lesins, Progressive Disease (PD) =>or =20% increase in sum of all target or any new lesions, SD=not CR, PR or PD.

2. Clinical Response Based on Serum Cancer Antigen 125 (CA-125) Concentration [From Baseline to up to 12 weeks (4 courses of therapy)]

   Ca-125 serum results compared from baseline to after patient's last treatment. This is a tumor biomarker. A decrease in results indicates a clinical response.

3. Change in Drug Resistance After Neoadjuvant Chemotherapy [Day 1 to Time to Surgery (Approximately Week 18)]

   As measured by extreme drug resistance assay - Unable to report due to tissue samples being incomplete or unsatisfactory to do laboratory testing.

4. Change in Thrombospondin-1 (TSP-1), p53, and Tumor Vessel Density [Week 18 (At surgery)]

   Unable to report due to incomplete (nonviable) or unsatisfactory tissue samples.

5. Quality of Life Score of Patients Receiving Neoadjuvant Chemotherapy [Day 1, Week 12 (after 4th course) , Week 16 (4 weeks after last treatment)]

   Functional Assessment of Cancer Therapy-Ovarian (FACT-O) Questionnaire was used to assess the impact of treatment- and disease-related factors on the quality of life of patients with ovarian cancers undergoing chemotherapy. It is a 5 point scale (from worse to best: 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much responses). Physical well-being, social/family well-being, functional well-being, emotional well-being and additional concerns questions are asked. Unable to evaluate; patients did not consistently complete the questionnaires.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with histological diagnosis of epithelial ovarian, primary peritoneal, or fallopian tube carcinoma for which no previous treatment has been given.

Patients with the following histological epithelial cell types are eligible:

• Serous adenocarcinoma

• Mucinous adenocarcinoma

• Clear cell adenocarcinoma

• Transitional cell

• Adenocarcinoma not otherwise specified

• Endometrioid adenocarcinoma

• Undifferentiated carcinoma

• Mixed epithelial carcinoma

• Malignant Brenner's tumor

• Measurable or non-measurable disease as defined by Solid Tumor Response Criteria (RECIST) within 4 weeks of study entry

• High-risk surgical candidate

• Gynecologic Oncology Group (GOG) performance status 0-3

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Creatinine ≤ 1.5 mg/dL

• Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)

• Bilirubin ≤ 1.5 times ULN

• Serum glutamic oxaloacetic transaminase (SGOT) ≤ 3 times ULN

• Life expectancy ≥ 12 weeks

Exclusion Criteria:

• Pregnant or nursing

• Positive pregnancy test -(Fertile patients must use effective nonhormonal contraception during and for 3 months after completion of study treatment.)

• History of another neoplasm except for non-metastatic, non-melanoma skin cancers, carcinoma in situ of the cervix, or cancer cured by surgery > 5 years prior to registration.

• Septicemia, severe infection, acute hepatitis, or severe gastrointestinal bleeding, defined as requiring blood transfusion or hospitalization at registration

• Unstable angina will not be eligible. Patients with evidence of abnormal cardiac conduction (e.g. bundle branch block, heart block) are eligible if their disease has been stable for the past six months.

• History of severe hypersensitivity or allergic reaction to study drugs, drugs formulated in Cremophor EL^®, other platinol compounds, or mannitol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• Masonic Cancer Center, University of Minnesota

Investigators

• Study Chair: Melissa A. Geller, MD, Masonic Cancer Center, University of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT00331422
• Other Study ID Numbers: 2004LS070; UMN-0409M64006; UMN- WCC-40
• First Posted: May 31, 2006
• Last Update Posted: Dec 28, 2017
• Last Verified: Dec 1, 2017

• Keywords provided by Masonic Cancer Center, University of Minnesota: ovarian clear cell cystadenocarcinoma; ovarian endometrioid adenocarcinoma; ovarian mixed epithelial carcinoma; ovarian mucinous cystadenocarcinoma; ovarian serous cystadenocarcinoma; ovarian undifferentiated adenocarcinoma; stage III ovarian epithelial cancer; stage IV ovarian epithelial cancer; peritoneal cavity cancer; fallopian tube cancer; Brenner tumor
• Additional relevant MeSH terms: Fallopian Tube Neoplasms; Peritoneal Neoplasms; Paclitaxel; Carboplatin

Study Results

Participant Flow

Arm/Group Title	Patients Who Received Treatment
Arm/Group Description	Includes all patients enrolled and treated with at least one dose of chemotherapy (carboplatin - dose calculated per Calvert formula - given intravenously for 30 minutes and/or paclitaxel 175 milligrams per meter squared over 3 hours).
Period Title: Overall Study
STARTED	7
COMPLETED	2
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Patients Who Received Treatment
Arm/Group Description	Includes all patients enrolled and treated with at least one dose of chemotherapy (carboplatin - dose calculated per Calvert formula - given intravenously for 30 minutes and/or paclitaxel 175 milligrams per meter squared over 3 hours).
Overall Participants	7
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	3 42.9%
>=65 years	4 57.1%
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	67
Sex: Female, Male (Count of Participants)
Female	7 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	7 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Who Underwent Optimal Cytoreduction After Chemotherapy
Description	These patients had their tumor(s) removed by surgery after receiving 4 cycles of chemotherapy to determine their response.
Time Frame	Week 18 (After 4 cycles of chemotherapy)

Outcome Measure Data

Analysis Population Description

Includes those patients that received 4 cycles of therapy before removal of cancerous tissue. Evaluation of overall response is not possible due to low number of patients and therefore could not obtain statistical significance.

Arm/Group Title	Evaluable Patients (Received 4 Cycles of Therapy and Surgery)
Arm/Group Description	Includes patients treated with 4 cycles of study chemotherapy regimen and surgery.
Measure Participants	2
Number [Participants]	2 28.6%

2. Secondary Outcome

Title	Patients' Overall Tumor Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST)
Description	Best response recorded from start of treatment until after 4th cycle of treatment. Defined by the sum of Complete Responses (CR), Partial Responses (PR), and Stable Disease (SD) in patients neoadjuvant chemotherapy. CR=disappearance of all lesions, PR=>or=30% decrease in sumof all target lesins, Progressive Disease (PD) =>or =20% increase in sum of all target or any new lesions, SD=not CR, PR or PD.
Time Frame	Week 16 (4 weeks after 4th course)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients Who Received Treatment
Arm/Group Description	Includes all patients enrolled and treated with at least one dose of chemotherapy (carboplatin - dose calculated per Calvert formula - given intravenously for 30 minutes and/or paclitaxel 175 milligrams per meter squared over 3 hours).
Measure Participants	7
Partial Response	2 28.6%
Progressive Disease	3 42.9%
Stable Disease	2 28.6%

3. Secondary Outcome

Title	Clinical Response Based on Serum Cancer Antigen 125 (CA-125) Concentration
Description	Ca-125 serum results compared from baseline to after patient's last treatment. This is a tumor biomarker. A decrease in results indicates a clinical response.
Time Frame	From Baseline to up to 12 weeks (4 courses of therapy)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients Who Received Treatment
Arm/Group Description	Includes all patients enrolled and treated with at least one dose of chemotherapy (carboplatin - dose calculated per Calvert formula - given intravenously for 30 minutes and/or paclitaxel 175 milligrams per meter squared over 3 hours).
Measure Participants	7
Increased Concentration	1 14.3%
Decreased Concentration	6 85.7%

4. Secondary Outcome

Title	Change in Drug Resistance After Neoadjuvant Chemotherapy
Description	As measured by extreme drug resistance assay - Unable to report due to tissue samples being incomplete or unsatisfactory to do laboratory testing.
Time Frame	Day 1 to Time to Surgery (Approximately Week 18)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients Who Received Treatment
Arm/Group Description	Includes all patients enrolled and treated with at least one dose of chemotherapy (carboplatin - dose calculated per Calvert formula - given intravenously for 30 minutes and/or paclitaxel 175 milligrams per meter squared over 3 hours).
Measure Participants	0

5. Secondary Outcome

Title	Change in Thrombospondin-1 (TSP-1), p53, and Tumor Vessel Density
Description	Unable to report due to incomplete (nonviable) or unsatisfactory tissue samples.
Time Frame	Week 18 (At surgery)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients Who Received Treatment
Arm/Group Description	Includes all patients enrolled and treated with at least one dose of chemotherapy (carboplatin - dose calculated per Calvert formula - given intravenously for 30 minutes and/or paclitaxel 175 milligrams per meter squared over 3 hours).
Measure Participants	0

6. Secondary Outcome

Title	Quality of Life Score of Patients Receiving Neoadjuvant Chemotherapy
Description	Functional Assessment of Cancer Therapy-Ovarian (FACT-O) Questionnaire was used to assess the impact of treatment- and disease-related factors on the quality of life of patients with ovarian cancers undergoing chemotherapy. It is a 5 point scale (from worse to best: 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much responses). Physical well-being, social/family well-being, functional well-being, emotional well-being and additional concerns questions are asked. Unable to evaluate; patients did not consistently complete the questionnaires.
Time Frame	Day 1, Week 12 (after 4th course) , Week 16 (4 weeks after last treatment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients Who Received Treatment
Arm/Group Description	Includes all patients enrolled and treated with at least one dose of chemotherapy (carboplatin - dose calculated per Calvert formula - given intravenously for 30 minutes and/or paclitaxel 175 milligrams per meter squared over 3 hours).
Measure Participants	0

Adverse Events

Time Frame	Adverse events were collected from Day 1 of treatment through 30 days post treatment or death, whichever came first.
Adverse Event Reporting Description	All events are reported; related and unrelated to study treatment.
Arm/Group Title	Patients Who Received Treatment
Arm/Group Description	Includes all patients enrolled and treated with at least one dose of chemotherapy (carboplatin - dose calculated per Calvert formula - given intravenously for 30 minutes and/or paclitaxel 175 milligrams per meter squared over 3 hours).
All Cause Mortality
	Patients Who Received Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Patients Who Received Treatment
	Affected / at Risk (%)	# Events
Total	6/7 (85.7%)
Cardiac disorders
Myocardial infarction	1/7 (14.3%)	1
Gastrointestinal disorders
Abdominal pain	1/7 (14.3%)	1
Bowel obstruction	3/7 (42.9%)	3
Dehydration	1/7 (14.3%)	1
Diarrhea	1/7 (14.3%)	1
Fistula, gastrointestinal	1/7 (14.3%)	1
Hemorrhage	1/7 (14.3%)	1
Nausea	1/7 (14.3%)	1
General disorders
Other, Failure to Thrive	1/7 (14.3%)	1
Pain	1/7 (14.3%)	1
Infections and infestations
Infection	2/7 (28.6%)	4
Nervous system disorders
Anxiety	1/7 (14.3%)	1
Confusion	1/7 (14.3%)	1
Neuropathy	1/7 (14.3%)	1
Renal and urinary disorders
Hydronephrosis	1/7 (14.3%)	1
Infection, bladder	1/7 (14.3%)	1
Renal insufficiency	1/7 (14.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/7 (14.3%)	1
Epistaxis	1/7 (14.3%)	1
Skin and subcutaneous tissue disorders
Wound complication	3/7 (42.9%)	3
Vascular disorders
Pulmonary embolism	2/7 (28.6%)	2
Other (Not Including Serious) Adverse Events
	Patients Who Received Treatment
	Affected / at Risk (%)	# Events
Total	7/7 (100%)
Blood and lymphatic system disorders
Anemia	2/7 (28.6%)	2
Neutropenia	4/7 (57.1%)	4
Peripheral Edema (limb)	1/7 (14.3%)	1
Thrombocytopenia	3/7 (42.9%)	3
Ear and labyrinth disorders
Tinnitus (ringing in ears)	1/7 (14.3%)	1
Eye disorders
Double Vision	1/7 (14.3%)	1
Gastrointestinal disorders
Diarrhea	1/7 (14.3%)	1
General disorders
Fatigue	2/7 (28.6%)	2
Infection	1/7 (14.3%)	1
Pain	1/7 (14.3%)	1
Musculoskeletal and connective tissue disorders
Hip Pain	1/7 (14.3%)	1
Nervous system disorders
Anxiety	2/7 (28.6%)	2
Sleep Apnea	1/7 (14.3%)	1
Respiratory, thoracic and mediastinal disorders
Oxygen, decreased (pulmonary-atelectasis)	1/7 (14.3%)	1
Skin and subcutaneous tissue disorders
Alopecia	7/7 (100%)	7

Limitations/Caveats

1 of the 2 evaluable patients was switched from Paclitaxel to Taxotere during the course of her treatment due to toxicity (adverse effects), but since it remains a platinum-based chemotherapy she is included in the evaluable group.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.