TEACO: Taxotere, Eloxatin, Avastin in Cancer of the Ovary

Study Overview
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Brief Summary
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Feasibility study to assess a novel combination of cytotoxic agents, docetaxel and oxaliplatin, as first-line therapy in the treatment of ovarian cancer and the impact of angiogenesis inhibition for the progression and prognosis of ovarian cancer by concurrent addition of bevacizumab (Avastin®).

Detailed Description
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Participants were administered study medication approximately 28 days after initial surgery for ovarian cancer received the study treatment regimen of up to one year unless there was disease progression, unacceptable toxicity, death, participant refusal, or treatment delay beyond the time frame permitted for each treatment Participants were followed for survival for a minimum 3 years from the date of enrollment

Official Title
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A Pilot Phase II Study Evaluating the Combination of Oxaliplatin and Docetaxel With Bevacizumab as First Line Therapy in Patients With FIGO Stage IB-IV Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Carcinoma

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: Bevacizumab (Avastin®)
* Drug: Docetaxel (Taxotere®)
* Drug: Oxaliplatin (Eloxatin®)


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Females 18 years of age or older Participants with a histologic diagnosis of ovarian, primary peritoneal, or fallopian tube carcinoma, Stage Ib- IV, with either optimal (≤ 1 cm residual disease) or suboptimal residual disease ( > 1 cm maximal diameter any remaining lesion) following initial surgery. Participants with the following histologic epithelial cell types are eligible: Serious adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma,undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma N.O.S. Participant must have adequate bone marrow function Participant must have adequate renal function Participant must have adequate urine protein/creatinine reaction (UPC) of <1.0; Participant must have adequate neurologic function Hepatic function: Total Bilirubin ≤ ULN; AST and ALT and Alkaline Phosphatase must be within the range allowing for eligibility. In determining eligibility the more abnormal of the two values (AST or ALT) should be used. Blood Coagulation parameters: PT such that international normalized ratio (INR) is < 1.5 (or an in-range INR, usually between 2 and 3, if a participant is on stable dose of therapeutic Warfarin or low molecular weight heparin) and a PTT < 1.2 times the upper limit normal. Participants must be enrolled in the study prior to 50 days (every effort will be made for prior to 28 days) after initial surgery performed for the combined purpose of diagnosis, staging and cytoreduction. Participants with measurable and non-measurable disease are eligible. Participants with suboptimal disease are eligible. Participants may or may not have cancer-related symptoms. Participants who have met the pre-entry requirements specified including serologic measurement of CA-125 as a baseline for subsequent determination of response using Rustin criteria. Participants with a GOG Performance Status of 0, 1, or 2. EXCLUSION CRITERIA: Participants with a current diagnosis of epithelial ovarian tumor of low malignant potential (Borderline carcinomas) are not eligible. Participants with a prior diagnosis of a low malignant potential tumor that was surgically resected and who subsequently develop invasive adenocarcinoma are eligible, provided that they have not received prior chemotherapy for any ovarian tumor. Germ cell tumors, sex cord-stromal tumors, carcinosarcomas, mixed mullerian tumors or carcinosarcomas, metastatic carcinomas from other sites to the ovary and low malignant potential tumors including so called micropapillary serous carcinomas are not eligible. Participants who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded. Prior radiation for localized cancer of the skin is permitted, provided that it was completed more than 5 years prior to enrollment, and the participant remains free of recurrent or metastatic disease. Participants who have received any prior anticancer chemotherapy or biologic therapy for any malignancy are excluded. Participants with synchronous primary endometrial cancer, or a past history of primary endometrial cancer, are excluded, unless all of the following conditions are met: Stage not greater than I-B; Less than 3 mm invasion without vascular or lymphatic invasion; No poorly differentiated subtypes, including papillary serous, clear cell, or other FIGO Grade 3 lesions. Participants with any history of cancer, with the exception of inclusion criteria #2 and #3, and non-melanoma skin cancer, who are cancer free for the last 5 years, are excluded. Participant with acute hepatitis or active infection that requires parenteral antibiotics. Participants with serious, non-healing wound, ulcer, or bone fracture. This includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days. Participants with granulating incisions healing by secondary intention with no evidence of fascial dehiscence or infection are eligible but require weekly wound examinations. Participants with active bleeding or pathologic conditions that carry high risk of bleeding,such as known bleeding disorder, coagulopathy, or tumor involving major vessels. Participants with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study. Participants with clinically significant cardiovascular disease. Participants with clinically significant proteinuria. Urine protein should be screened by urinalysis. Participants discovered to have a urine protein: serum creatinine ratio greater than or equal to 1 should undergo a 24-hour urine collection, which must be an adequate collection and must demonstrate < 1000 mg protein/24 hr to allow participation in the study. Participants with or with anticipation of invasive procedures. Participants with GOG Performance Grade of 3 or 4. Participants who are pregnant or nursing. Participants with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies and hypersensitivity to polysorbate 80 or hypersensitivity to any of the study drugs and its ingredients. Participants who participated in a study with any investigational product/device within the last 30 days. Any medical condition that in the judgment of the investigator would jeopardize any participant safety or the study drug evaluation for efficacy and safety.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxaliplatin/Docetaxel/Bevacizumab<br>Participants with International Federation of Gynecology and Obstetrics (FIGO) stage IB through IV ovarian, primary peritoneal, or fallopian tube carcinoma treated with Oxaliplatin, Docetaxel, and Bevacizumab - 28 days after initial surgery | Drug: Bevacizumab (Avastin®)<br>* 15 mg/kg bevacizumab administered intravenously (IV) over 30 to 90 minutes on Day 1 of every 3 week cycle for 12 months or until disease progression or unacceptable toxicity<br>Drug: Docetaxel (Taxotere®)<br>* 75 mg/m^2 docetaxel was administered IV over 1 hour on Day 1 of every 3 week cycle for 6 cycles or until disease progression or unacceptable toxicity<br>Drug: Oxaliplatin (Eloxatin®)<br>* 85 mg/m^2 Oxaliplatin was administered IV over 2 hours on Day 1 of every 3 week cycle for 6 cycles or until disease progression or unacceptable toxicity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Twelve-month Progression-free Survival (PFS) Rate in Participants | Tumor assessments were performed by Computed tomography (CT) and Magnetic Resonance Imaging (MRI) to evaluate disease progression based on Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST). Disease progression was recorded as any one of the following: appearance of a new lesion symptomatic deterioration progression of target or nontarget lesions death Participants who did not die or show show disease progression achieved PFS. PFS rate is the percent of participants who achieved PFS. | up to 12 months following treatment initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Twenty Four-month Progression-free Survival (PFS) Rate in Participants | Tumor assessments were performed by Computed tomography (CT) and Magnetic Resonance Imaging (MRI) to evaluate disease progression based on Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST). Disease progression was recorded as any one of the following: appearance of a new lesion symptomatic deterioration progression of target or nontarget lesions death Participants who did not die or show show disease progression achieved PFS. PFS rate is the percent of participants who achieved PFS. | up to 24 months following treatment initiation | 
| Median Time to Progression-free Survival (PFS) | Time to PFS was the interval from the date of registration to the earliest date of disease progression or death, whichever occurred first. Time of PFS was censored on the last available tumor assessment date for participants leaving the study prior to disease progression or death; and also for participants requiring off-study medication or additional debulking surgery (where assessment date used was the one prior to off-study medication or surgery), at Day 1, for living participants with no post-baseline tumor assessments. Median PFS was estimated from a Kaplan-Meier curve. | up to approximately 1300 days following treatment initiation | 
| Tumor Response Rate Based on Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST) | Tumors were assessed by CT and MRI. Tumor response was evaluated by GOG RECIST in which: Complete response (CR) was the disappearance of all target and non-target lesions, with no evidence of new lesions Partial response (PR) was at least a 30% decrease in the sum of longest dimensions (LD) of all measurable target lesions Participants with a response (CR or PR) were to have the initial response confirmed by tumor imaging in 4-6 weeks. | up to 12 months following treatment initiation | 
| Twelve-month Recurrence-free Survival (RFS) Rate in Participants With Non Measurable Disease at Baseline | Participants with Recurrence-free survival (RFS) were participants with a non-measurable disease at baseline, who had not achieved disease progression nor had died. Disease progression included the following: the appearance of a new lesion symptomatic deterioration progression of non-target lesions a predefined serum CA 125 increase. RFS rate was the percent of participants in the non-measurable disease subgroup who achieved RFS. | up to 12 months following treatment initiation | 
| Median Time to Recurrence-free Survival (RFS) in Participants With Non-measurable Disease at Baseline | The time to RFS was programmatically defined as the interval from the date of registration to the earliest date of disease progression or death, whichever occurred first. Participants were censored on the last available CA 125 biomarker blood draw date if left the study prior to disease progression or death they received off-study anti-tumor medication underwent debulking surgery censored at Day 1 if they were alive had no post baseline CA 125 biomarker blood draw. | up to approximately 1500 days following treatment initiation | 
| CA-125 Response Rate | A CA-125 response was considered at least a 50% reduction in the level of the biomarker, CA-125, from a pretreatment level, which was confirmed and maintained for at least 28 days. The overall CA-125 biomarker response rate was defined as the number of participants in the measurable disease subgroup who met the above criteria at least once within the study treatment period +21 days, divided by the number of evaluable participants in the disease subgroup. | up to 12 months after treatment initiation | 
| Overall Survival Rate | Survival was the observed length of life from entry into the study to death or the date of last contact. The overall survival rate (percentage of participants showing survival) at 12 and 24-months is reported here. | up to up to approximately 1700 days after treatment initiation | 
| Median Overall Survival Time | Survival was the observed length of life from entry into the study to death or the date of last contact. The median overall survival time was estimated using Kaplan-Meier Curve. | up to approximately 1700 days after treatment initiation |