Intraperitoneal Therapy For Ovarian Cancer With Carboplatin Trial

Fallopian Tube Cancer Clinical Trial

— iPocc  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01506856
• Other study ID #: GOTIC-001/JGOG3019
• Secondary ID: UMIN000003670jRC
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: May 2010
• Est. completion date: February 28, 2021

Study information

• Verified date: September 2022
• Source: Gynecologic Oncology Trial & Investigation Consortium
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is a randomized, multicenter international study. Patient are stratified according to Residual tumor diameter([0cm(No residual)] vs. [0cm2 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 655
• Est. completion date: February 28, 2021
• Est. primary completion date: February 28, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Epithelial Ovarian Cancer
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Neoplasms
• Primary Peritoneal Carcinoma

Intervention

Drug:
• Paclitaxel(intravenous) + Carboplatin(intravenous)
Paclitaxel(intravenous) + Carboplatin(intravenous) Paclitaxel : 80mg/m2, IV infusion, Day1, 8, and 15 Carboplatin: AUC=6.0, IV infusion, Day1 A total of 6 to 8 cycles will be repeated.
• Paclitaxel(intravenous) + Carboplatin(intraperitoneal)
Paclitaxel(intravenous) + Carboplatin(intraperitoneal) Paclitaxel : 80mg/m2, IV infusion, Day1, 8, and 15 Carboplatin: AUC=6.0, IP injection, Day1 A total of 6 to 8 cycles will be repeated.

Locations

Country	Name	City	State
Hong Kong	Queen Mary Hospital	Hong Kong	High West
Japan	Hyogo Cancer Center	Akashi	Hyogo
Japan	Juntendo University Hospital	Bunkyo	Tokyo
Japan	The University of Tokyo Hospital	Bunkyo-Ku	Tokyo
Japan	Aichi Cancer Center Hospital	Chikusa	Aichi
Japan	NHO Kyusyu Medical center	Fukuoka
Japan	Saitama Medical University International Medical Center	Hidaka	Saitama
Japan	Japanese Red Cross Society Himeji Hospital	Himeji	Hyogo
Japan	Hirosaki University School of Medicine & Hospital	Hirosaki-shi	Aomori
Japan	JA Hiroshima General Hospital	Hiroshima
Japan	Tokai University Hospital	Isehara	Kanagawa
Japan	Kagoshima City Hospital	Kagoshima
Japan	Kaizuka City Hospital	Kaizuka	Osaka
Japan	Nara Medical University Hospital	Kashihara	Nara
Japan	The Jikei University School of Medicine, Kashiwa Hospital	Kashiwa	Chiba
Japan	Saitama Medical University Saitama Medical Center	Kawagoe	Saitama
Japan	Nippon Medical University Musasi Kosugi Hospital	Kawasaki-shi	Kanagawa
Japan	Kobe City Medical Center General Hospital	Kobe	Hyogo
Japan	The Jikei University Daisan Hospital	Komae	Tokyo
Japan	The Cancer Institute Hospital Of JFCR	Koto-Ku	Tokyo
Japan	NHO Kure Medical Center And Chugoku Cancer Center	Kure	Hiroshima
Japan	University Hospital, Kyoto Prefectural University of Medicine	Kyoto
Japan	Gunma University Hospital	Maebashi	Gunma
Japan	Shinshu University Hospital	Matsumoto	Nagano
Japan	NHO Shikoku Cancer Center	Matsuyama	Ehime
Japan	The Jikei University Hospital	Minato-Ku	Tokyo
Japan	Miyoshi Central Hospital	Miyoshi	Hiroshima
Japan	Iwate Medical University Hospital	Morioka	Iwate
Japan	Shizuoka Cancer Center	Nagaizumi	Shizuoka
Japan	Saiseikai Nagasaki Hospital	Nagasaki
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Niigata University Medical & Dental Hospital	Niigata
Japan	Hyogo Medical College Hospital	Nishinomiya	Hyogo
Japan	Osaka Medical Center for Cancer and Cardiovascular Diseases	Osaka
Japan	Gunma Prefectural Cancer Center	Ota	Gunma
Japan	Tohoku University Hospital	Sendai	Miyagi
Japan	Jichi Medical University Hospital	Shimotsuke	Tochigi
Japan	Showa University Hospital	Shinagawa-Ku	Tokyo
Japan	Keio University Hospital	Shinjuku-Ku	Tokyo
Japan	Tokyo Women's Medical University Medical Center East	Shinjuku-Ku	Tokyo
Japan	Osaka University Hospital	Suita	Osaka
Japan	Osaka Medical College Hospital	Takatsuki	Osaka
Japan	Ehime University Hospital	Toon-shi	Ehime
Japan	Tottori Municipal Hospital	Tottori
Japan	Mie University Hospital	Tsu	Mie
Japan	Tsukuba University Hospital	Tsukuba	Ibaraki
Japan	Yamaguchi University Hospital	Ube	Yamaguchi
Japan	Okinawa Prefectural Chubu Hospital	Uruma	Okinawa
Japan	Tochigi Cancer Center	Utsunomiya	Tochigi
Japan	Mie Prefectural General Medical Center	Yokkaichi	Mie
Japan	Yokohama Municipal Citizen's Hospital	Yokohama	Kanagawa
Japan	Tottori University	Yonago	Tottori
Japan	University of Fukui Hospital	Yoshida	Fukui
Korea, Republic of	Gangnam Severance Hospital in Korea	Dogok	Seoul
Korea, Republic of	Asan Medical Center	P'ungnap-tong	Seoul
Korea, Republic of	Korea Cancer Center Hospital	Seoul	Gongneung-Dong
Korea, Republic of	Shinchon Severance Hospital	Seoul	Shinchon
Korea, Republic of	Ewha Womans University Medical Center	Yangcheon	Seoul
New Zealand	University of Otago - Christchurch/Christchurch Women's Hospital	Christchurch
Singapore	KK Women's and Children's Hospital	Bukit Timah
Singapore	National University Hospital of Singapore	Kent Ridge
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Gynecologic Oncology Trial & Investigation Consortium	Japanese Gynecologic Oncology Group

Countries where clinical trial is conducted

United States,  Hong Kong,  Japan,  Korea, Republic of,  New Zealand,  Singapore, 

References & Publications (13)

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. — View 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. — View 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. — View 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. — View Citation

Demets DL. Futility approaches to interim monitoring by data monitoring committees. Clin Trials. 2006;3(6):522-9. doi: 10.1177/1740774506073115. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival(PFS)		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	Overall survival (OS)		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
Secondary	Tumor response (only patients with evaluable disease)		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
Secondary	Adverse events		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
Secondary	Treatment completion rate		After the last cycle of the protocol teatment
Secondary	Quality of Life (QOL) assessments		baseline, after 3 cycles, 6 cycles, 36 week, 60 weeks and 84 weeks from the start of protocol treatment
Secondary	Cost-utility analysis		baseline, after 3 cycles, 6 cycles, 36 week, 60 weeks and 84 weeks from the start of protocol treatment

External Links

•   Gynecologic Oncology Trial and Investigation Consortium [Japanese only]
•   Japanese Gynecologic Oncology Group