HIPEC After Initial CRS in Patients Who Have Received NACT

NCT03540017 | Unknown Phase 1 FDA Drug

• 1 other identifier: IRB #: 18-0153
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The majority of women diagnosed with ovarian, fallopian tube and primary peritoneal cancer present with advanced stage III and IV disease. Despite aggressive surgery and systemic chemotherapy, the majority of patients will relapse. Five year survival remains only 20-35% for patients diagnosed with bulky stage IIIC and IV cancers. Patients who are not candidates for an initial cytoreductive surgery at the time of diagnosis form a particularly poor prognosis group. These patients are treated with neoadjuvant chemotherapy (NACT) and will ultimately undergo cytoreductive surgery provided there is a response to chemotherapy. New therapies for this cohort of women are urgently needed. The investigators have designed a pilot study to evaluate the feasibility of heated intraoperative peritoneal chemotherapy (HIPEC) given at the time of interval cytoreductive surgery after 3 cycles of NACT. Patients undergoing NACT for ovarian, fallopian tube or primary peritoneal cancer will be evaluated after their third cycle of chemotherapy for trial participation. Patient meeting eligibility criteria will proceed with cytoreductive surgery. HIPEC will be administered in those patients in whom optimal tumor cytoreduction is achieved. Primary objective of this study is to evaluate the feasibility, toxicity and tolerability of HIPEC administered after NACT.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma

Keywords

Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer

Outcome Measures

Primary Outcomes (3)

• Morbidity, assessed by the occurrence of adverse events and serious adverse events

  Severity of adverse events will be evaluated using the NCI Common Terminology Criteria for Adverse Events version 4.0 \[NCI CTCAE v4.0\]. AEs will be classified as possibly, probably, or definitely related to study treatment.

  30 days

• Safety data obtained from scheduled exams

  Physical examinations, vital signs, hematologic and clinical parameters, measured monthly for 12 months after initial study treatment or subject discontinuation, whichever comes first.

  1 year

• Mortality

  Time from surgery date to death due to any cause.

  5 years

Secondary Outcomes (5)

• Progression-free survival

  5 years

• Ability to complete systemic IV chemotherapy after IDS and HIPEC

  1 year

• Functional Assessment of Cancer Therapy-Ovarian (FACT-O)

  2 years

• Completeness of surgical cytoreduction

  24 hours

• Achievement of hyperthermia

  24 hours

Study Arms (1)

HIPEC

EXPERIMENTAL

Patient will receive HIPEC in the form of Cisplatin 100mg/m2. 5. HIPEC will be provided at completion of surgical cytoreduction. The chemotherapy will be ordered by the treating gynecologic oncologist. It will be prepared in the chemotherapy pharmacy and delivered to the operating room once the surgeon confirms optimal cytoreduction and eligibility. Patients undergoing bowel resection will be left with bowel in discontinuity during the HIPEC infusion cycle. The abdomen will be temporarily closed with skin staples to prevent spillage of the perfusate. HIPEC will be delivered using the closed technique as has been well described.

Drug: Cisplatin

Interventions

Cisplatin DRUG

Heated Intraperitoneal Chemotherapy will be administered after the completion of interval cytoreductive surgery after three cycles of neoadjuvant chemotherapy.

HIPEC

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed cancer of the ovary, fallopian tube or peritoneum.
• Women of all races and ethnicities are eligible for this trial.
• Age \> 18.
• The patient must have documented disease limited to the abdomen and pelvis that is amenable to complete CRS indicated by:
• Disease confined to the peritoneal surfaces.
• No clinical or radiological evidence of hematogenous or distant (extra-abdominal) nodal metastasis.
• Evidence of response to NACT must as documented by at least one of the following: decline in serum CA125 level, at least a 30% decrease in the sum of the longest diameter of target lesions on radiographic imaging, or resolution of ascites or pleural effusion(s).
• Gynecologic Oncology Group (GOG) performance status \<= 2
• Leukocytes \>= 3,000/microliter (mcL), absolute neutrophil count \>= 1,500/mcL, platelets \>= 100,000/mcL
• Adequate hepatic function as measured by total bilirubin within normal institutional limits, aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT))/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT)) =\< 2.5 x institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min for patients with creatinine levels above institutional normal
• Albumin \>= 2.5 mg/dL
• Satisfactory cardiopulmonary function (no history of severe congestive heart failure or severe pulmonary disease, as indicated by clinically acceptable risks to undergo major abdominal surgery
• Voluntary participation after getting written informed consent

You may not qualify if:

• Prior chemotherapy (other than NACT) or whole abdomen radiation for ovarian, fallopian tube or primary peritoneal cancers.
• Patients with an active second malignancy regardless of site.
• Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or breast-feeding patients
• Patients who are receiving other oncologic investigational therapeutic agents
• Patients receiving NACT whose disease has progressed following at least 3 cycles of platinum-based therapy, defined by at least one of the following: clinical deterioration (new or worsening of existing ascites, carcinomatous ileus, malignant bowel obstruction, declining performance status); new lesion(s) or increase in maximal diameter of \> 20% of the two largest target lesions; rising CA-125 (an increase of at least 10% of baseline value that increases over 3 values obtained every 21 days).
• Cardiac or pulmonary conditions that preclude aggressive cytoreductive surgery.
• Patients found to have non-gynecologic cancer at the time of surgery.
• Patients with gynecologic malignancy of low-grade serous or borderline histology.

Sponsors & Collaborators

• Northwell Health: lead
• Katie Oppo Research Fund: collaborator

Study Sites (1)

Long Island Jewish Medical Center

New Hyde Park, New York, 11040, United States

RECRUITING

Related Publications (18)

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  PMID: 23747291 RESULT

• Gomez-Hidalgo NR, Martinez-Cannon BA, Nick AM, Lu KH, Sood AK, Coleman RL, Ramirez PT. Predictors of optimal cytoreduction in patients with newly diagnosed advanced-stage epithelial ovarian cancer: Time to incorporate laparoscopic assessment into the standard of care. Gynecol Oncol. 2015 Jun;137(3):553-8. doi: 10.1016/j.ygyno.2015.03.049. Epub 2015 Mar 28.

  PMID: 25827290 RESULT

• Horowitz NS, Miller A, Rungruang B, Richard SD, Rodriguez N, Bookman MA, Hamilton CA, Krivak TC, Maxwell GL. Does aggressive surgery improve outcomes? Interaction between preoperative disease burden and complex surgery in patients with advanced-stage ovarian cancer: an analysis of GOG 182. J Clin Oncol. 2015 Mar 10;33(8):937-43. doi: 10.1200/JCO.2014.56.3106. Epub 2015 Feb 9.

  PMID: 25667285 RESULT

• Zivanovic O, Sima CS, Iasonos A, Hoskins WJ, Pingle PR, Leitao MM Jr, Sonoda Y, Abu-Rustum NR, Barakat RR, Chi DS. The effect of primary cytoreduction on outcomes of patients with FIGO stage IIIC ovarian cancer stratified by the initial tumor burden in the upper abdomen cephalad to the greater omentum. Gynecol Oncol. 2010 Mar;116(3):351-7. doi: 10.1016/j.ygyno.2009.11.022.

  PMID: 20022092 RESULT

• Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res. 1996;82:359-74. doi: 10.1007/978-1-4613-1247-5_23.

  PMID: 8849962 RESULT

• Spiliotis J, Halkia EE, Kalantzi N, Giassas S, Lianos E, Efstathiou E, Sugarbaker PH. Mapping the location of peritoneal metastases using the peritoneal cancer index and the correlation with overall survival: a retrospective study. J BUON. 2015 May;20 Suppl 1:S64-70.

  PMID: 26051335 RESULT

• Vergote I, Trope CG, Amant F, Kristensen GB, Ehlen T, Johnson N, Verheijen RH, van der Burg ME, Lacave AJ, Panici PB, Kenter GG, Casado A, Mendiola C, Coens C, Verleye L, Stuart GC, Pecorelli S, Reed NS; European Organization for Research and Treatment of Cancer-Gynaecological Cancer Group; NCIC Clinical Trials Group. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010 Sep 2;363(10):943-53. doi: 10.1056/NEJMoa0908806.

  PMID: 20818904 RESULT

• Kehoe S, Hook J, Nankivell M, Jayson GC, Kitchener H, Lopes T, Luesley D, Perren T, Bannoo S, Mascarenhas M, Dobbs S, Essapen S, Twigg J, Herod J, McCluggage G, Parmar M, Swart AM. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet. 2015 Jul 18;386(9990):249-57. doi: 10.1016/S0140-6736(14)62223-6. Epub 2015 May 19.

  PMID: 26002111 RESULT

• Wright AA, Bohlke K, Armstrong DK, Bookman MA, Cliby WA, Coleman RL, Dizon DS, Kash JJ, Meyer LA, Moore KN, Olawaiye AB, Oldham J, Salani R, Sparacio D, Tew WP, Vergote I, Edelson MI. Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016 Oct 1;34(28):3460-73. doi: 10.1200/JCO.2016.68.6907. Epub 2016 Aug 8.

  PMID: 27502591 RESULT

• Meyer LA, Cronin AM, Sun CC, Bixel K, Bookman MA, Cristea MC, Griggs JJ, Levenback CF, Burger RA, Mantia-Smaldone G, Matulonis UA, Niland JC, O'Malley DM, Wright AA. Use and Effectiveness of Neoadjuvant Chemotherapy for Treatment of Ovarian Cancer. J Clin Oncol. 2016 Nov 10;34(32):3854-3863. doi: 10.1200/JCO.2016.68.1239.

  PMID: 27601552 RESULT

• 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.

  PMID: 8960474 RESULT

• 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.

  PMID: 11181662 RESULT

• 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.

  PMID: 16394300 RESULT

• Eoh KJ, Lee JY, Nam EJ, Kim S, Kim YT, Kim SW. Long-Term Survival Analysis of Intraperitoneal versus Intravenous Chemotherapy for Primary Ovarian Cancer and Comparison between Carboplatin- and Cisplatin-based Intraperitoneal Chemotherapy. J Korean Med Sci. 2017 Dec;32(12):2021-2028. doi: 10.3346/jkms.2017.32.12.2021.

  PMID: 29115086 RESULT

• Cascales-Campos P, Gil J, Feliciangeli E, Parrilla P. HIPEC in ovarian cancer: treatment of a new era or is it the end of the pipeline? Gynecol Oncol. 2015 Nov;139(2):363-8. doi: 10.1016/j.ygyno.2015.06.012. Epub 2015 Jun 16.

  PMID: 26091936 RESULT

• Trimble EL, Christian MC. Intraperitoneal chemotherapy for women with advanced epithelial ovarian carcinoma. Gynecol Oncol. 2006 Jan;100(1):3-4. doi: 10.1016/j.ygyno.2005.12.006. No abstract available.

  PMID: 16368439 RESULT

• van Driel WJ, Koole SN, Sikorska K, Schagen van Leeuwen JH, Schreuder HWR, Hermans RHM, de Hingh IHJT, van der Velden J, Arts HJ, Massuger LFAG, Aalbers AGJ, Verwaal VJ, Kieffer JM, Van de Vijver KK, van Tinteren H, Aaronson NK, Sonke GS. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N Engl J Med. 2018 Jan 18;378(3):230-240. doi: 10.1056/NEJMoa1708618.

  PMID: 29342393 RESULT

• Gouy S, Ferron G, Glehen O, Bayar A, Marchal F, Pomel C, Quenet F, Bereder JM, Le Deley MC, Morice P. Results of a multicenter phase I dose-finding trial of hyperthermic intraperitoneal cisplatin after neoadjuvant chemotherapy and complete cytoreductive surgery and followed by maintenance bevacizumab in initially unresectable ovarian cancer. Gynecol Oncol. 2016 Aug;142(2):237-42. doi: 10.1016/j.ygyno.2016.05.032. Epub 2016 Jun 2.

  PMID: 27246305 RESULT

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

Cisplatin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Jill Whyte, MD

  Northwell Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jill S Whyte, MD

CONTACT

5165624438; jwhyte@northwell.edu

Aaron Nizam, MD

CONTACT

anizam1@northwell.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician

Study Record Dates

• First Submitted: April 16, 2018
• First Posted: May 30, 2018
• Study Start: March 12, 2019
• Primary Completion: July 5, 2024
• Study Completion: July 5, 2025
• Last Updated: November 2, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)