Clinical trial NCT01644825: Weekly Paclitaxel With or Without Pazopanib in Platinum Resistant or Refractory Ovarian Cancer
Official title: MITO-11: A Randomized Multicentre Phase II Trial With Pazopanib and Weekly Paclitaxel vs Weekly Paclitaxel in Platinum Resistant or Refractory Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: platinum resistant
platinum refractory
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
First posted: 2012-07-19
Enrollment: 72
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
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 to evaluate the safety and activity of adding pazopanib to weekly chemotherapy with paclitaxel for patients with ovarian cancer that is resistant or refractory to treatment with platinum based therapy.


Eligibility criteria: Inclusion Criteria:

* Cytologic / histologic diagnosis of stage IC-IV ovarian cancer
* Disease progressed during first line chemotherapy or disease relapsed within 6 months after the last platinum treatment
* Disease evaluable by RECIST or Ca 125 GCIG criteria
* No residual peripheral neurotoxicity from previous chemotherapy treatment
* PS 0-1
* Aged at least 18 and not greater than 75 years.
* Life expectancy of at least 3 months
* Able to swallow and retain oral medication
* Written informed consent prior to performance of study specific procedures or assessments
* Ability and willingness to comply with treatment and follow up assessments and procedures

Exclusion Criteria:

· • Previous or concomitant malignant neoplasia (not including basocellular or spinocellular skin carcinoma or in-situ carcinoma of the uterine cervix, provided they are being adequately treated)

* Previous treatment with weekly paclitaxel
* More than 2 previous chemotherapy treatments
* Serious heart disease, including heart failure, atrioventricular block of any degree, serious arrhythmia or history of any one or more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, symptomatic peripheral vascular disease, coronary artery by-pass graft surgery, class II, III or IV congestive heart failure as defined by the New York Heart Association (NYHA)
* Hemoglobin \< 9 g/dL, neutrophils \< 1500/mm3, platelets \< 100000/mm3
* Impairment of renal function (patients should have 2 functioning kidneys): creatinine 1.5 times the upper normal limit - UNL; calculated creatinine clearance \< 50 mL/min; urine protein to creatinine ratio \> or = 1: then, a 24-hour urine protein must be assessed and subject must have a 24-hour urine protein value \<1gr to be eligible
* Impairment of liver function (SGOT or SGPT \> or = 2.5 UNL, alkaline phosphatase \> 2.5 ULN, total bilirubin \> 1.5 times the UNL)
* Prothrombin time (PT) or international normalized ratio (INR) or activated partial thromboplastin time (PTT) \> 1.2 times the UNL
* Pregnancy, breast feeding, or inadequate contraception
* Unable to discontinue prohibited medications (see protocol section 6.7)
* Clinically significant gastrointestinal abnormalities which might interfere with oral dosing, including but not limited to malabsorption syndrome, major resection of the stomach or small bowel that could affect drug absorption, active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, other gastrointestinal conditions with increased risk of perforation, history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment, signs or symptoms of GI obstruction
* Any unstable or serious concurrent condition
* Prolongation of corrected QT interval (QTc) \>480 ms
* History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
* Macroscopic hematuria
* Major surgery or trauma within 30 days
* Hypertension uncontrolled with adequate therapy (systolic blood pressure (BP) of \> or = 140mmHg, or diastolic BP of \> or = 90mmHg)
* Any ongoing toxicity from prior anti-cancer therapy that is \>Grade 1 and/or that is progressing in severity
* Present or suspected haemorrhagic syndromes
* Patients' inability to access the centre due to area of residence

Primary outcomes:
measure: progression free survival
timeFrame: 6 months from randomization
Secondary outcomes:
measure: number of patients with objective response
timeFrame: at 2 months and 4 months after randomization
measure: worst grade toxicity per patient
timeFrame: at end of each 28 day cycle of therapy
measure: overall survival
timeFrame: one year from randomization
Other outcomes:
Locations:
city: Acquaviva delle Fonti
country: Italy
facility: Osp. Regionale Mulli
city: Arezzo
country: Italy
facility: Ospedale San donato
city: Benevento
country: Italy
facility: A.O. G. Rummo
city: Bologna
country: Italy
facility: Ospedale Bellaria
city: Brindisi
country: Italy
facility: Ospedale Senatore Antonio Perrino
city: Catania
country: Italy
facility: A.O. Garibaldi Nesimadi Catania
city: Faenza
country: Italy
facility: Ospedale Civile di Faenza
city: Ferrara
country: Italy
facility: A.O.U. Arcispedale Sant'Anna di Ferrara
city: Frosinone
country: Italy
facility: Ospedale Fabrizio Spaziani della ASL di Frosinone
city: Lugo
country: Italy
facility: Ospedale Umbero I
city: Milano
country: Italy
facility: Istituto Nazionale Tumori
city: Modena
country: Italy
facility: A.O. Univeristaria Policlinico
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori , Oncologia Medica - Dipartimento Uro-Ginecologico
city: Napoli
country: Italy
facility: Seconda Universita di Napoli
city: Perugia
country: Italy
facility: Ospedale Silvestrini
city: Ravenna
country: Italy
facility: Ospedale S. Maria delle Croci AUSL di Ravenna
city: Reggio Calabria
country: Italy
facility: A.O. Bainchi Melacrino Morelli Osp. Riuniti
city: Rimini
country: Italy
facility: Ospedale degli Infermi, P.O. Ospedale Civile
city: Roma
country: Italy
facility: Policlinico Umberto I
city: Roma
country: Italy
facility: Policlinico Universitario Gemelli Università Cattolica del Sacro Cuore
Study officials:
affiliation: National Cancer Institute, Naples
name: Sandro Pignata, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute, Naples
name: Francesco Perrone, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Campania Luigi Vanvitelli
name: Ciro Gallo, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pignata S, Lorusso D, Scambia G, Sambataro D, Tamberi S, Cinieri S, Mosconi AM, Orditura M, Brandes AA, Arcangeli V, Panici PB, Pisano C, Cecere SC, Di Napoli M, Raspagliesi F, Maltese G, Salutari V, Ricci C, Daniele G, Piccirillo MC, Di Maio M, Gallo C, Perrone F; MITO 11 investigators. Pazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer (MITO 11): a randomised, open-label, phase 2 trial. Lancet Oncol. 2015 May;16(5):561-8. doi: 10.1016/S1470-2045(15)70115-4. Epub 2015 Apr 14.