Efficacy Study of Chemotherapy to Treat Ovarian Cancer Recurrence by Prolonging the Platinum Free Interval (MITO-8)

• ClinicalTrials.gov Identifier: NCT00657878
• Recruitment Status: Unknown
• First Posted: April 14, 2008
• Last Update Posted: October 29, 2015
• Sponsor: National Cancer Institute, Naples
• Information provided by (Responsible Party): National Cancer Institute, Naples

Tracking Information

• First Submitted Date: April 8, 2008
• First Posted Date: April 14, 2008
• Last Update Posted Date: October 29, 2015
• Study Start Date: November 2008
• Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 20, 2008): overall survival [ Time Frame: 18 months ]
• Original Primary Outcome Measures (submitted: April 8, 2008): overall survival

Current Secondary Outcome Measures (submitted: June 27, 2012)

• progression free survival [ Time Frame: 18 months ]
• changes in quality of life [ Time Frame: 9 months ]
  quality of life is measured at baseline and at 3 months and 6 months after patient begins study
• number of objective responses [ Time Frame: 6 months ]
• worst grade toxicity for each patient [ Time Frame: 6 months ]

Original Secondary Outcome Measures (submitted: April 8, 2008)

• progression free survival
• quality of life [ Time Frame: at baseline and after 3rd and 6th cycles of chemotherapy ]
• response rate [ Time Frame: after 3rd and 6th cycles of chemotherapy ]
• toxicity [ Time Frame: at each cycle of chemotherapy ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy Study of Chemotherapy to Treat Ovarian Cancer Recurrence by Prolonging the Platinum Free Interval
• Official Title: Liposomal Doxorubicin Versus Carboplatin/Paclitaxel in Patients With Ovarian Cancer Recurrence Between 6 and 12 Months After Previous Platinum Based Therapy: Phase III Randomized Multicenter Study Amendment Title Protocol Version 2.0: Phase III International Multicenter Randomized Study Testing the Effect on Survival of Prolonging Platinum-free Interval in Patients With Ovarian Cancer Recurring Between 6 and 12 Months After Previous Platinum Based Chemotherapy.
• Brief Summary: This study aims to test the hypothesis that the artificial prolongation of the platinum-free interval with a non-platinum treatment will improve the effectiveness of overall therapy in patients with ovarian cancer progression occurring 6-12 months after first-line treatment with a platinum-derivative.

Detailed Description

Ovarian cancer is the most deadly gynecologic cancer. Though many patients respond well initially to chemotherapy, most of them in time will suffer a relapse. Patients often receive multiple lines of chemotherapy for their recurrences, and the choice of chemotherapy depends largely on the time interval since the last therapy. Patients whose disease recurs longer than 12 months after a platinum containing treatment are considered to be platinum sensitive, and are candidates for retreatment with a platinum regimen.

Patients in whom disease recurs less than 6 months after a platinum containing treatment are considered platinum resistant or refractory, and are treated with a non platinum chemotherapy. The option of treatment is less clear for patients whose disease recurs between 6 and 12 months after platinum containing therapy. It is hypothesized that prolonging the interval since last platinum treatment by using a non platinum chemotherapy will result in better outcomes for these patients.

This study will evaluate if the experimental sequence of a non platinum based chemotherapy, followed at a later progression by a platinum based chemotherapy is superior, in terms of the effect on overall survival, to the standard inverse sequence of treatment.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Ovarian Cancer

Intervention

• Drug: stealth liposomal doxorubicin
  stealth liposomal doxorubicin 40 mg/m2 IV day 1 every 28 days
• Drug: carboplatin
  carboplatin AUC 5 IV day 1 every 21 days
• Drug: paclitaxel
  paclitaxel 175 mg/m2 IV day 1 every 21 days
• Drug: Topotecan
  dosing and schedule according to Institutional guidelines
• Drug: Gemcitabine
  1000 mg/m2 on days 1,8,15 every 28 days

Study Arms

• Experimental: non platinum based chemotherapy
  a non platinum based therapy (corresponding to stealth liposomal doxorubicin, or topotecan, or gemcitabine,or any other drug approved in clinical practice for the treatment of patients with ovarian cancer after previous platinum-based chemotherapy) followed by a platinum based chemotherapy at disease progression
  Interventions:

  • Drug: stealth liposomal doxorubicin
  • Drug: carboplatin
  • Drug: paclitaxel
  • Drug: Topotecan
  • Drug: Gemcitabine
• Active Comparator: platinum based chemotherapy
  platinum based chemotherapy (corresponding to the combination of carboplatin + paclitaxel, or carboplatin + gemcitabine for patients with significant but lower than grade 3 neuropathy at baseline) followed by a non platinum based chemotherapy at disease progression
  Interventions:

  • Drug: stealth liposomal doxorubicin
  • Drug: carboplatin
  • Drug: paclitaxel
  • Drug: Topotecan
  • Drug: Gemcitabine

• Publications *: Piccirillo MC, Scambia G, Bologna A, Signoriello S, Vergote I, Baumann K, Lorusso D, Murgia V, Sorio R, Ferrandina G, Sacco C, Cormio G, Breda E, Cinieri S, Natale D, Mangili G, Pisano C, Cecere SC, Di Napoli M, Salutari V, Raspagliesi F, Arenare L, Bergamini A, Bryce J, Daniele G, Gallo C, Pignata S, Perrone F. Quality-of-life analysis of the MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG study comparing platinum-based versus non-platinum-based chemotherapy in patients with partially platinum-sensitive recurrent ovarian cancer. Ann Oncol. 2018 May 1;29(5):1189-1194. doi: 10.1093/annonc/mdy062.

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: October 28, 2015): 215
• Original Estimated Enrollment (submitted: April 8, 2008): 250
• Estimated Study Completion Date: June 2017
• Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histological or cytological diagnosis of ovarian cancer
• Disease recurrence between 6 and 12 months after a first-line platinum based therapy
• Indication for chemotherapy, but no more than 2 previous lines of previous therapy
• Life expectancy of more than 3 months

Exclusion Criteria:

• Previous or concomitant malignant malignancy (excluding adequately treated baso-or squamocellular carcinoma of the skin and carcinoma in situ of the cervix)
• ECOG Performance Status at least 3
• Previous treatment with stealth liposomal doxorubicin
• Residual peripheral neuropathy Grade 3 or higher
• Heart disease (congestive heart failure, myocardial infarction within 6 months from study entry, atrioventricular block of any grade, severe arrhythmias)
• Neutrophils < 2000 x mm3, platelets < 100000 x mm3
• Inadequate renal function (creatinine no greater than 1.25 x normal values) or liver function (ALT or AST no greater than 1.25 x normal values)
• Present or suspected hemorrhagic syndromes
• Inability to comply with protocol and follow-up
• Inability to access study site for clinical visits
• Refusal of informed consent

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Germany, Italy

Administrative Information

• NCT Number: NCT00657878
• Other Study ID Numbers: MITO-8; 2008-001755-22 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Cancer Institute, Naples
• Original Responsible Party: Sandro Pignata, National Cancer Institute Naples
• Current Study Sponsor: National Cancer Institute, Naples
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Sandro Pignata, M.D., Ph.D.; National Cancer Institute, Naples
• Principal Investigator: Francesco Perrone, M.D., Ph.D.; National Cancer Institute, Naples
• Principal Investigator: Marilina Piccirillo, M.D.; National Cancer Institute, Naples
• Principal Investigator: Ciro Gallo, M.D., Ph.D.; University of Campania "Luigi Vanvitelli"

• PRS Account: National Cancer Institute, Naples
• Verification Date: October 2015