GOG-0262: A Phase III Trial of Every-3-Weeks Paclitaxel Versus Dose Dense Weekly Paclitaxel in Combination With Carboplatin With or Without Concurrent and Consolidation Bevacizumab (NSC #704865) in the Treatment of Primary Stage II, III or IV Epithelial Ovarian, Peritoneal or Fallopian Tube Cancer and ACRIN 6695: Perfusion CT Imaging to Evaluate Treatment Response in Patients Participating in GOG-0262
概览
- 阶段
- 3 期
- 干预措施
- Bevacizumab
- 疾病 / 适应症
- Fallopian Tube Endometrioid Adenocarcinoma
- 发起方
- National Cancer Institute (NCI)
- 入组人数
- 692
- 试验地点
- 1123
- 主要终点
- Progression-Free Survival
- 状态
- 进行中（未招募）
- 最后更新
- 19天前
概览
简要总结
This phase III clinical trial studies two different dose schedules of paclitaxel to see how well they work in combination with carboplatin with or without bevacizumab in treating patients with stage II, III or IV ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bevacizumab is a type of drug called a monoclonal antibody and blocks tumor growth by stopping the growth of blood vessels that tumors need to grow. It is not yet known whether giving paclitaxel with combination chemotherapy once every three weeks is more effective than giving paclitaxel once a week in treating patients with ovarian, primary peritoneal, or fallopian tube cancer.
详细描述
PRIMARY OBJECTIVES: I. To determine if the weekly paclitaxel regimen increases the time until first progression or death (progression-free survival \[PFS\]) compared to the every-3-week paclitaxel regimen in women with primary stage II, III or IV epithelial ovarian, peritoneal or fallopian tube cancer who are receiving carboplatin with or without bevacizumab. SECONDARY OBJECTIVES: I. To determine if the weekly paclitaxel increases the duration of overall survival compared to the every-3-week paclitaxel when combined with carboplatin with or without bevacizumab. II. To compare the weekly paclitaxel to the every-3-week paclitaxel with respect to the incidence of severe or serious adverse events when it is combined with carboplatin with or without bevacizumab. III. To compare the weekly paclitaxel to the every-3-week paclitaxel with respect to patients' self-reported quality of life (QOL) as measured by the Functional Assessment of Cancer Therapy-Ovarian (FACT-O)-Trial Outcome Index (TOI), when paclitaxel is combined with carboplatin with or without bevacizumab. (As of 02/08/2012, the QOL portion of this study is complete; patients enrolled after this date will not have QOL assessments) TRANSLATIONAL RESEARCH OBJECTIVES: I. To evaluate single nucleotide polymorphisms (SNPs) associated with progression-free survival and toxicity in advanced stage epithelial ovarian, peritoneal and fallopian tube cancer using genome wide association studies (GWAS).\* II. To evaluate genomic signatures in tumor tissues which are predictive for patient survival in advanced stage epithelial ovarian, peritoneal and fallopian tube cancer.\* III. To evaluate the association between serum and plasma biomarkers and response to anti-angiogenesis therapy in advanced stage epithelial ovarian, peritoneal, and fallopian tube cancer.\* NOTE: \*As of 02/08/2012, the translational research (TR) portion of this study is complete; patients enrolled after this date will not have TR specimens collected. IMAGING PRIMARY OBJECTIVES: I. To determine whether larger changes in the tumor perfusion parameters from baseline timepoint (T0) to early-therapy T2 are prognostic of higher progression-free survival (PFS) rate at 6 months (PFS-6) from enrollment in patients treated with weekly or every-3-week paclitaxel regimens, who are receiving carboplatin with or without bevacizumab.\*\*\* IMAGING SECONDARY OBJECTIVES: I. To determine whether larger changes in tumor perfusion parameters from baseline T0 to intermediate T1 and from T1 to T2 are prognostic of higher PFS-6 in patients treated with weekly or every-3-week paclitaxel regimens, who are receiving carboplatin with or without bevacizumab.\*\*\* II. To determine whether larger changes in tumor perfusion parameters values from T0 to T1, T0 to T2, and T1 to T2 are prognostic of better overall survival in all treatment arms.\*\*\* III. To assess the association between changes in tumor perfusion parameters before and after chemotherapy initiation (T0 to T1) and subsequent best tumor response according to standard anatomic Response Evaluation Criteria in Solid Tumors (RECIST).\*\*\* IV. To assess the association between tumor perfusion parameters before chemotherapy and subsequent best tumor response according to RECIST, PFS-6, and overall survival.\*\*\* V. To test the assumption that tumor perfusion parameters are reliable, user-independent, and reproducible parameters of tumor microvascular characteristics; a subgroup of 15 patients will have repeat computed tomography (CT) perfusion studies at the intermediate T1 time point.\*\*\* NOTE: \*\*\*Patients enrolled after February 8, 2012 must participate in the ACRIN 6695 component at ACRIN-qualified institutions. OUTLINE: Patients are randomized to 1 of 2 treatment arms (beginning on 04-30-2012, the trial is no longer randomized and the chemotherapy regimen is selected and declared prior to enrolling in the study). ARM I (adjuvant chemotherapy suboptimally debulked): Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. ARM II (neoadjuvant chemotherapy with interval cytoreductive surgery): Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Patients undergo interval cytoreductive surgery between courses 3 and 4. Patients in both arms may receive optional\*\* bevacizumab IV over 30-90 minutes on day 1 beginning in course 2. Courses of bevacizumab repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients in Arm II receive bevacizumab during courses 2, 5, and 6 only. NOTE: \*\*Before enrolling onto this study, each patient chooses whether the study treatment will include concurrent and maintenance bevacizumab. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
研究者
入排标准
入选标准
- •Primary Surgery and Neoadjuvant Chemotherapy with Interval Cytoreductive Surgery Patients:
- •Patients must have measurable disease; at least one target lesion must have a minimum length of 1 cm in both the long and short axis (determined at the local site); for primary surgery patients, if no radiographic evidence of measurable disease is obtained prior to registration this can be based on surgical findings; imaging then would need to be completed in the 14 days between Gynecology Oncology Group (GOG) registration and chemotherapy initiation
- •After GOG registration, the American College of Radiology \[ACR\] Imaging Core Laboratory will confirm target lesion as required per protocol; the GOG-eligibility (RECIST) scan and baseline T0 perfusion CT scans will be reviewed prior to the intermediate T1 perfusion CT time point
- •Primary Surgery Patients:
- •Patients with a histologic diagnosis of epithelial ovarian cancer, peritoneal primary carcinoma or fallopian tube cancer, stage II -IV suboptimally debulked (any residual disease \> 1 cm); International Federation of Gynecology and Obstetrics (FIGO) stage is assessed following the completion of initial abdominal surgery, appropriate imaging studies and with appropriate tissue available for histologic evaluation; the minimum surgery required is an abdominal surgery providing tissue for histologic evaluation and establishing and documenting the primary site and stage; if additional surgery was performed, it should have been in accordance with appropriate surgery for ovarian or peritoneal carcinoma described in the GOG Surgical Procedures Manual
- •Neoadjuvant Chemotherapy (NAC) with Interval Cytoreductive Surgery (ICS) Patients:
- •For patients undergoing NAC-ICS, a core tissue (not fine needle aspiration) biopsy is required; the tissue must be consistent with a Müllerian origin; patients will require documentation of at least stage II or extraovarian sites of disease acquired via imaging or surgery (without attempt at cytoreduction)
- •Patients with the following histologic epithelial cell types are eligible: serous, endometrioid, clear cell, mucinous adenocarcinoma, undifferentiated carcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified (N.O.S.); however, the histologic features of the tumor must be compatible with a primary Müllerian epithelial adenocarcinoma; patients may have co-existing fallopian tube carcinoma in-situ so long as the primary origin of invasive tumor is ovarian, peritoneal or fallopian tube; of note, patients with clear cell and mucinous tumors will be eligible unless there is a higher priority protocol
- •Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl; this ANC cannot have been induced or supported by granulocyte colony stimulating factors
- •Platelets greater than or equal to 100,000/mcl
排除标准
- •Patients with a current diagnosis of borderline epithelial ovarian tumor (formerly "tumors of low malignant potential") or recurrent invasive epithelial ovarian, primary peritoneal or fallopian tube cancer treated with surgery only (such as patients with stage I-A or I-B low grade epithelial ovarian or fallopian tube cancers) are not eligible; patients with a prior diagnosis of a borderline tumor that was surgically resected and who subsequently develop an unrelated, new invasive epithelial ovarian, peritoneal primary or fallopian tube cancer are eligible, provided that they have not received prior chemotherapy for any ovarian tumor
- •Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
- •Patients who have received prior chemotherapy for any abdominal or pelvic tumor including neo-adjuvant chemotherapy for their ovarian, primary peritoneal or fallopian tube cancer; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
- •Patients who have received any targeted therapy (including but not limited to vaccines, antibodies, tyrosine kinase inhibitors) or hormonal therapy for management of their epithelial ovarian, fallopian tube or peritoneal primary cancer
- •Patients with synchronous primary endometrial cancer, or a past history of primary endometrial cancer, unless all of the following conditions are met: stage not greater than I-A, grade 1 or 2, no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell or other FIGO grade 3 lesions
- •With the exception of non-melanoma skin cancer, patients with other invasive malignancies who had (or have) any evidence of the other cancer present within the last five years or whose previous cancer treatment contraindicates this protocol therapy
- •Patients with acute hepatitis or active infection that requires parenteral antibiotics
- •Patients with clinically significant cardiovascular disease; this includes:
- •Myocardial infarction or unstable angina \< 6 months prior to registration
- •New York Heart Association (NYHA) grade II or greater congestive heart failure
研究组 & 干预措施
Arm I (adjuvant chemotherapy suboptimally debulked)
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses.
干预措施: Bevacizumab
Arm I (adjuvant chemotherapy suboptimally debulked)
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses.
干预措施: Carboplatin
Arm I (adjuvant chemotherapy suboptimally debulked)
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses.
干预措施: Computed Tomography
Arm I (adjuvant chemotherapy suboptimally debulked)
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses.
干预措施: Paclitaxel
Arm I (adjuvant chemotherapy suboptimally debulked)
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses.
干预措施: Therapeutic Conventional Surgery
Arm II (neoadjuvant chemotherapy)
Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Patients undergo interval cytoreductive surgery between courses 3 and 4.
干预措施: Carboplatin
Arm II (neoadjuvant chemotherapy)
Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Patients undergo interval cytoreductive surgery between courses 3 and 4.
干预措施: Computed Tomography
Arm II (neoadjuvant chemotherapy)
Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Patients undergo interval cytoreductive surgery between courses 3 and 4.
干预措施: Bevacizumab
Arm II (neoadjuvant chemotherapy)
Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Patients undergo interval cytoreductive surgery between courses 3 and 4.
干预措施: Paclitaxel
Arm II (neoadjuvant chemotherapy)
Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Patients undergo interval cytoreductive surgery between courses 3 and 4.
干预措施: Therapeutic Conventional Surgery
结局指标
主要结局
Progression-Free Survival
时间窗: The timeframe is from enrollment onto the study up to 3 years following enrollment.
First progression or death for weekly paclitaxel treatment relative to standard 3 week paclitaxel. Progression is defined using response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
次要结局
- Median Duration of First Quartile Survival(The timeframe is from enrollment onto the study up to 3 years after enrollment)
- Quality of Life Score as Measured by Functional Assessment of Cancer Therapy-Ovary-Total Outcome Index (Fact-O TOI)(18 weeks after enrolling on the study, which is the time it takes to complete 6 cycles of treatment plus 3 weeks)