Clinical trial NCT01506856: Intraperitoneal Therapy For Ovarian Cancer With Carboplatin Trial
Official title: A Randomized Phase II/III Trial of Intravenous (IV) Paclitaxel Weekly Plus IV Carboplatin Once Every 3 Weeks Versus IV Paclitaxel Weekly Plus Intraperitoneal (IP) Carboplatin Once Every 3 Weeks in Women With Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Epithelial Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Carcinoma
Keywords: Epithelial ovarian cancer
Fallopian tube cancer
peritoneal cancer
intraperitoneal therapy
Carboplatin
Paclitaxel
Lead sponsor: Gynecologic Oncology Trial & Investigation Consortium
Sponsor class: NETWORK
Collaborators: name: Japanese Gynecologic Oncology Group
First posted: 2012-01-10
Enrollment: 655
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is:

Phase A: To confirm the feasibility of paclitaxel administered by intravenous (IV) infusion weekly plus concurrent carboplatin administered by intraperitoneal (IP) injection once every 3 weeks (dd-TCip therapy).

Phase B: To compare the efficacy and safety of the following two treatment regimens as first-line chemotherapy in women with epithelial ovarian, Fallopian tube or primary peritoneal cancer.

Detailed description: This is a randomized, multicenter international study. Patient are stratified according to Residual tumor diameter(\[0cm(No residual)\] vs. \[0cm\<residual\<1cm\] vs. \[1cm\<residual\<2cm\] vs. \[\>2 cm\]), FIGO stage(StageII vs. III vs. IV) and institution. Patient randomized to one of the treatment arms described below.

RegimenI(Standard treatment: dd-TCiv therapy): Paclitaxel administered by IV infusion weekly plus concurrent carboplatin administered by IV infusion once every 3 weeks

RegimenII(Study treatment: dd-TCip therapy): Paclitaxel administered by IV infusion weekly plus concurrent carboplatin administered by IP injection once every 3 weeks

The 3-week period (21 days) is 1 cycle. Protocol treatment basically comprises 6 cycles. IDS is allowed to be performed after 3, 4 or 5 cycles of the protocol treatment. In such cases, the protocol treatment must be restarted within 8 weeks after IDS. If IDS is performed, patients can receive up to 3 additional cycles of the protocol treatment after IDS. If interval debulking surgery (IDS) is performed after 3, 4 or 5 cycles, the patients can receive up to 3 additional cycles of the protocol treatment. A total of 6 to 8 cycles will be repeated.

The analysis of efficacy will be performed on all randomized subjects in accordance with the intention-to-treat (ITT) principle. In order to assess the robustness of the results, the same analyses will be done using all randomized subjects who satisfy the eligibility criteria. The analysis of safety will be performed on all subjects who have received at least one dose of study treatment.

Eligibility criteria: Inclusion Criteria:

1. Patients assumed to have a stageII-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer as a pre-surgery diagnosis
2. Patients scheduled to undergo laparotomy

   \*Both optimal and suboptimal patients will be eligible for the study (Suboptimal patients, as well as those who undergo only exploratory laparotomy, are eligible.)
3. ECOG Performance Status: 0-2
4. Patients who provide consent for placement of the IP port system, if randomized to Regimen II (Study treatment: dd-TCip therapy)
5. Patients expected to receive the first protocol treatment within 8 weeks after the comprehensive staging surgery
6. Lab data and clinical examination: Data within 28 days before the scheduled date of surgery

   * Neutrophil count ≧ 1,500 /mm3
   * Platelet count ≧ 100,000 /mm3
   * AST (GOT) ≦ 100 IU/L
   * ALT (GPT) ≦ 100 IU/L
   * Total bilirubin \< 1.5 mg/dL
   * Serum Creatinine \< 1.5 mg/dL
   * Electrocardiogram (ECG): Patients with normal ECG, Asymptomatic patients with abnormal ECGs not requiring medical intervention
   * Neuropathy(Both motor and sensory) ≦ Grade1 (CTCAE Version 4.0)
7. Patients expected to survive longer than 3 months from the start date of the protocol treatment
8. Patients aged 20 years and older at the time of tentative registration (with no upper age limit)
9. Patients who provide written informed consent for participation in this trial

Exclusion Criteria:

1. Patients assumed to have a borderline malignancy of the ovary, fallopian tube, or primary peritoneal cancer
2. Patients who have received previous chemotherapy or radiation therapy to treat the current disease
3. Patients who have a synchronous malignancy or who have been progression-free less than 5 years for a metachronous malignancy (Patients with basal and squamous cell carcinoma of the skin, as well as carcinoma in situ, and intramucosal carcinoma cured by local treatment, are eligible for the study)
4. Patients with serious medical complications, such as serious heart disease, cerebrovascular accidents, uncontrolled diabetes mellitus, uncontrolled hypertension, pulmonary fibrosis, interstitial pneumonitis, active bleeding, an active gastrointestinal ulcer, or a serious neurological disorder
5. Patients who have had a hypersensitivity reaction to polyoxyethylated or hydrogenated castor oil
6. Patients with a pleural effusion requiring continuous drainage
7. Patients with an active infection requiring antibiotics
8. Patients who are pregnant, nursing or of child-bearing potential
9. Patients with evidence upon physical examination of brain tumor and any brain metastases
10. Patients for whom completion of this study and/or follow-up is deemed inappropriate for any reason
11. Patients with any signs/symptoms of interstitial pneumonia

Primary outcomes:
measure: Progression-free survival(PFS)
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed until 510 events are observed or until 3 years from the last patient is randomized to the study
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: weekly during the protocl treatment, then every 3 months for the first 2 years, 6-month for the following 2 years, and once a year thereafter
measure: Tumor response (only patients with evaluable disease)
timeFrame: every 2 cycles [after 2 cycles, after 4 cycles, after 6 cycles, (after 8 cycles)], the time of discontinuation of the protocol treatment and then at least annually during follow-up
measure: Adverse events
timeFrame: weekly during the protocl treatment, then every 3 months for the first 2 years, 6-month for the following 2 years, and once a year thereafter
measure: Treatment completion rate
timeFrame: After the last cycle of the protocol teatment
measure: Quality of Life (QOL) assessments
timeFrame: baseline, after 3 cycles, 6 cycles, 36 week, 60 weeks and 84 weeks from the start of protocol treatment
measure: Cost-utility analysis
timeFrame: baseline, after 3 cycles, 6 cycles, 36 week, 60 weeks and 84 weeks from the start of protocol treatment
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
state: High West
city: Chikusa
country: Japan
facility: Aichi Cancer Center Hospital
state: Aichi
city: Hirosaki-shi
country: Japan
facility: Hirosaki University School of Medicine & Hospital
state: Aomori
city: Kashiwa
country: Japan
facility: The Jikei University School of Medicine, Kashiwa Hospital
state: Chiba
city: Matsuyama
country: Japan
facility: NHO Shikoku Cancer Center
state: Ehime
city: Toon-shi
country: Japan
facility: Ehime University Hospital
state: Ehime
city: Yoshida
country: Japan
facility: University of Fukui Hospital
state: Fukui
city: Maebashi
country: Japan
facility: Gunma University Hospital
state: Gunma
city: Ōta
country: Japan
facility: Gunma Prefectural Cancer Center
state: Gunma
city: Kure
country: Japan
facility: NHO Kure Medical Center And Chugoku Cancer Center
state: Hiroshima
city: Miyoshi
country: Japan
facility: Miyoshi Central Hospital
state: Hiroshima
city: Akashi
country: Japan
facility: Hyogo Cancer Center
state: Hyogo
city: Himeji
country: Japan
facility: Japanese Red Cross Society Himeji Hospital
state: Hyogo
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Nishinomiya
country: Japan
facility: Hyogo Medical College Hospital
state: Hyogo
city: Tsukuba
country: Japan
facility: Tsukuba University Hospital
state: Ibaraki
city: Morioka
country: Japan
facility: Iwate Medical University Hospital
state: Iwate
city: Isehara
country: Japan
facility: Tokai University Hospital
state: Kanagawa
city: Kawasaki-shi
country: Japan
facility: Nippon Medical University Musasi Kosugi Hospital
state: Kanagawa
city: Yokohama
country: Japan
facility: Yokohama Municipal Citizen's Hospital
state: Kanagawa
city: Tsu
country: Japan
facility: Mie University Hospital
state: Mie
city: Yokkaichi
country: Japan
facility: Mie Prefectural General Medical Center
state: Mie
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Matsumoto
country: Japan
facility: Shinshu University Hospital
state: Nagano
city: Kashihara
country: Japan
facility: Nara Medical Univeｒsity Hospital
state: Nara
city: Uruma
country: Japan
facility: Okinawa Prefectural Chubu Hospital
state: Okinawa
city: Kaizuka
country: Japan
facility: Kaizuka City Hospital
state: Osaka
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Takatsuki
country: Japan
facility: Osaka Medical College Hospital
state: Osaka
city: Hidaka
country: Japan
facility: Saitama Medical University International Medical Center
state: Saitama
city: Kawagoe
country: Japan
facility: Saitama Medical University Saitama Medical Center
state: Saitama
city: Nagaizumi
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Shimotsuke
country: Japan
facility: Jichi Medical University Hospital
state: Tochigi
city: Utsunomiya
country: Japan
facility: Tochigi Cancer Center
state: Tochigi
city: Bunkyo
country: Japan
facility: Juntendo University Hospital
state: Tokyo
city: Bunkyō-Ku
country: Japan
facility: The University of Tokyo Hospital
state: Tokyo
city: Komae
country: Japan
facility: The Jikei University Daisan Hospital
state: Tokyo
city: Koto-Ku
country: Japan
facility: The Cancer Institute Hospital Of JFCR
state: Tokyo
city: Minato-Ku
country: Japan
facility: The Jikei University Hospital
state: Tokyo
city: Shinagawa-Ku
country: Japan
facility: Showa University Hospital
state: Tokyo
city: Shinjuku-Ku
country: Japan
facility: Keio University Hospital
state: Tokyo
city: Shinjuku-Ku
country: Japan
facility: Tokyo Women's Medical University Medical Center East
state: Tokyo
city: Yonago
country: Japan
facility: Tottori University
state: Tottori
city: Ube
country: Japan
facility: Yamaguchi University Hospital
state: Yamaguchi
city: Fukuoka
country: Japan
facility: NHO Kyusyu Medical center
city: Hiroshima
country: Japan
facility: JA Hiroshima General Hospital
city: Kagoshima
country: Japan
facility: Kagoshima City Hospital
city: Kyoto
country: Japan
facility: University Hospital, Kyoto Prefectural University of Medicine
city: Nagasaki
country: Japan
facility: Saiseikai Nagasaki Hospital
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Niigata
country: Japan
facility: Niigata University Medical & Dental Hospital
city: Osaka
country: Japan
facility: Osaka Medical Center for Cancer and Cardiovascular Diseases
city: Tottori
country: Japan
facility: Tottori Municipal Hospital
city: Seoul
country: Korea, Republic of
facility: Korea Cancer Center Hospital
state: Gongneung-Dong
city: Dogok
country: Korea, Republic of
facility: Gangnam Severance Hospital in Korea
state: Seoul
city: P'ungnap-tong
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul
city: Yangcheon
country: Korea, Republic of
facility: Ewha Womans University Medical Center
state: Seoul
city: Seoul
country: Korea, Republic of
facility: Shinchon Severance Hospital
state: Shinchon
city: Christchurch
country: New Zealand
facility: University of Otago - Christchurch/Christchurch Women's Hospital
city: Bukit Timah
country: Singapore
facility: KK Women's and Children's Hospital
city: Kent Ridge
country: Singapore
facility: National University Hospital of Singapore
Study officials:
affiliation: Saitama Medical University International Medical Center Comprehensive Cancer Center
name: Keiichi Fujiwara, MD, PhD
role: STUDY_CHAIR
References:
citation: Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol. 2002 Mar 1;20(5):1248-59. doi: 10.1200/JCO.2002.20.5.1248.
citation: Neijt JP, Engelholm SA, Tuxen MK, Sorensen PG, Hansen M, Sessa C, de Swart CA, Hirsch FR, Lund B, van Houwelingen HC. Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer. J Clin Oncol. 2000 Sep;18(17):3084-92. doi: 10.1200/JCO.2000.18.17.3084.
citation: Piccart MJ, Bertelsen K, James K, Cassidy J, Mangioni C, Simonsen E, Stuart G, Kaye S, Vergote I, Blom R, Grimshaw R, Atkinson RJ, Swenerton KD, Trope C, Nardi M, Kaern J, Tumolo S, Timmers P, Roy JA, Lhoas F, Lindvall B, Bacon M, Birt A, Andersen JE, Zee B, Paul J, Baron B, Pecorelli S. Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J Natl Cancer Inst. 2000 May 3;92(9):699-708. doi: 10.1093/jnci/92.9.699.
citation: Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, Mannel RS, DeGeest K, Hartenbach EM, Baergen R; Gynecologic Oncology Group. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2003 Sep 1;21(17):3194-200. doi: 10.1200/JCO.2003.02.153. Epub 2003 Jul 14.
citation: Katsumata N, Yasuda M, Takahashi F, Isonishi S, Jobo T, Aoki D, Tsuda H, Sugiyama T, Kodama S, Kimura E, Ochiai K, Noda K; Japanese Gynecologic Oncology Group. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009 Oct 17;374(9698):1331-8. doi: 10.1016/S0140-6736(09)61157-0. Epub 2009 Sep 18.
citation: Alberts DS, Liu PY, Hannigan EV, O'Toole R, Williams SD, Young JA, Franklin EW, Clarke-Pearson DL, Malviya VK, DuBeshter B. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med. 1996 Dec 26;335(26):1950-5. doi: 10.1056/NEJM199612263352603.
citation: Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, Wadler S, Sickel J. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001 Feb 15;19(4):1001-7. doi: 10.1200/JCO.2001.19.4.1001.
citation: Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, Copeland LJ, Walker JL, Burger RA; Gynecologic Oncology Group. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006 Jan 5;354(1):34-43. doi: 10.1056/NEJMoa052985.
citation: Miyagi Y, Fujiwara K, Kigawa J, Itamochi H, Nagao S, Aotani E, Terakawa N, Kohno I; Sankai Gynecology Study Group (SGSG). Intraperitoneal carboplatin infusion may be a pharmacologically more reasonable route than intravenous administration as a systemic chemotherapy. A comparative pharmacokinetic analysis of platinum using a new mathematical model after intraperitoneal vs. intravenous infusion of carboplatin--a Sankai Gynecology Study Group (SGSG) study. Gynecol Oncol. 2005 Dec;99(3):591-6. doi: 10.1016/j.ygyno.2005.06.055. Epub 2005 Aug 10.
citation: Fujiwara K, Armstrong D, Morgan M, Markman M. Principles and practice of intraperitoneal chemotherapy for ovarian cancer. Int J Gynecol Cancer. 2007 Jan-Feb;17(1):1-20. doi: 10.1111/j.1525-1438.2007.00809.x.
citation: Demets DL. Futility approaches to interim monitoring by data monitoring committees. Clin Trials. 2006;3(6):522-9. doi: 10.1177/1740774506073115.
citation: Huang HQ, Brady MF, Cella D, Fleming G. Validation and reduction of FACT/GOG-Ntx subscale for platinum/paclitaxel-induced neurologic symptoms: a gynecologic oncology group study. Int J Gynecol Cancer. 2007 Mar-Apr;17(2):387-93. doi: 10.1111/j.1525-1438.2007.00794.x.
citation: Calvert AH, Newell DR, Gumbrell LA, O'Reilly S, Burnell M, Boxall FE, Siddik ZH, Judson IR, Gore ME, Wiltshaw E. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol. 1989 Nov;7(11):1748-56. doi: 10.1200/JCO.1989.7.11.1748.