Carboplatin-based Chemotherapy With or Without Panitumumab in Platinum-sensitive Recurrent Ovarian Cancer (PROVE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by WiSP Wissenschaftlicher Service Pharma GmbH
Sponsor:
Collaborator:
ClinAssess GmbH
Information provided by (Responsible Party):
WiSP Wissenschaftlicher Service Pharma GmbH
ClinicalTrials.gov Identifier:
NCT01388621
First received: May 17, 2011
Last updated: August 19, 2013
Last verified: August 2013
  Purpose

The purpose of this trial is to estimate the therapeutic efficacy of the experimental targeted regimen including the EGFR antibody panitumumab (in combination with carboplatin and either pegylated liposomal doxorubicin or gemcitabine) in relation to the respective standard combination in patients with a KRAS wildtype with platinum-sensitive recurrent ovarian cancer. It is expected that the progression free survival rate at 12 months is improved by the targeted regimen.


Condition Intervention Phase
Ovarian Cancer
Drug: Panitumumab
Drug: pegylated liposomal doxorubicin (PLD)
Drug: Carboplatin
Drug: Gemcitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: PROVE A Randomized Phase II Trial of Standard Carboplatin-based Chemotherapy With or Without Panitumumab in Platinum-sensitive Recurrent Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by WiSP Wissenschaftlicher Service Pharma GmbH:

Primary Outcome Measures:
  • Progression-free survival (PFS) rate after 12 months. [ Time Frame: 12 month ] [ Designated as safety issue: No ]
    PFS is defined as the time from randomisation to the time of disease progression or relapse (according to RECIST, not CA-125 only!) or death, or to the date of last tumor assessment without any such event (censored observation).


Secondary Outcome Measures:
  • Duration of Tumor-Response [ Time Frame: Duration of Therapy (Therapy is planned for 6 cycles of 3 resp. 4 weeks each, shorter or longer durations are possible) ] [ Designated as safety issue: No ]
    according to RECIST, including measurable disease patients only, and including patients with CA-125 defined disease as well

  • Progression-free survival [ Time Frame: End of Follow-up (up to 1 year) ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: End of Follow-up (up to 1 year) ] [ Designated as safety issue: No ]
  • Maximum toxicity resp. AE grade per patient per toxicity resp. AE during therapy [ Time Frame: Duration of Therapy (Therapy is planned for 6 cycles of 3 resp. 4 weeks each, shorter or longer durations are possible) ] [ Designated as safety issue: Yes ]

    Toxicities resp. (S)AE during therapy will be documented, reported and analyzed according to NCI CTC 3.0 with special focus on skin toxicity.

    Results are given as maximum grade per patient per toxicity resp. AE during therapy.


  • Tumor Response Rate [ Time Frame: Duration of Therapy (Therapy is planned for 6 cycles of 3 resp. 4 weeks each, shorter or longer durations are possible) ] [ Designated as safety issue: No ]
    according to RECIST, including measurable disease patients only, and including patients with CA-125 defined disease as well


Estimated Enrollment: 140
Study Start Date: October 2011
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental arm (A):

Caelyx 30 mg/m² d1 Carboplatin AUC 5 d1 Panitumumab 6 mg/kg/KG d1 + 15 q4w until progressive disease or for a max. of 6 cycles

OR

Gemcitabine 1000 mg/m² d1 + 8 Carboplatin AUC 4 d1 Panitumumab 9 mg/kg/KG d1 q3w until progressive disease or for a max. of 6 cycles

The backbone chemotherapy (Caelyx or Gemcitabine-based) is specified by the investigator before randomization of a patient.

Drug: Panitumumab
Panitumumab 6 mg/kg/BW d1 + 15 q4w until progressive disease or for a max. of 6 cycles In case of CR, PR or SD at the end of the combination treatment in experimental arm, panitumumab monotherapy is to be continued with 9 mg/kg/BW d1 q3w until time of tumor progression or up to a maximum of 6 months.
Other Name: Vectibix
Drug: pegylated liposomal doxorubicin (PLD)
pegylated liposomal doxorubicin (PLD) 30 mg/m² d1 q4w until progressive disease or for a max. of 6 cycles
Other Name: Caelyx
Drug: Carboplatin
Carboplatin AUC 5 d1 q4w until progressive disease or for a max. of 6 cycles
Other Name: multiple generics in existence
Drug: Gemcitabine
gemcitabine 1000 mg/m² d1 + 8 q3w until progressive disease or for a max. of 6 cycles
Other Name: Gemzar
Drug: Carboplatin
Carboplatin AUC 4 d1 q3w until progressive disease or for a max. of 6 cycles
Other Name: multiple generics in existence
Drug: Panitumumab
Panitumumab 9 mg/kg/BW d1 q3w until progressive disease or for a max. of 6 cycles In case of CR, PR or SD at the end of the combination treatment in experimental arm, panitumumab monotherapy is to be continued with 9 mg/kg/BW d1 q3w until time of tumor progression or up to a maximum of 6 months.
Other Name: Vectibix
Active Comparator: Standard arm (B):

Caelyx 30 mg/m² d1 Carboplatin AUC 5 d1 q4w until progressive disease or for a max. of 6 cycles

OR

Gemcitabine 1000 mg/m² d1 + 8 Carboplatin AUC 4 d1 q3w until progressive disease or for a max. of 6 cycles

The backbone chemotherapy (Caelyx or Gemcitabine-based) is specified by the investigator before randomization of a patient.

Drug: pegylated liposomal doxorubicin (PLD)
pegylated liposomal doxorubicin (PLD) 30 mg/m² d1 q4w until progressive disease or for a max. of 6 cycles
Other Name: Caelyx
Drug: Carboplatin
Carboplatin AUC 5 d1 q4w until progressive disease or for a max. of 6 cycles
Other Name: multiple generics in existence
Drug: Gemcitabine
gemcitabine 1000 mg/m² d1 + 8 q3w until progressive disease or for a max. of 6 cycles
Other Name: Gemzar
Drug: Carboplatin
Carboplatin AUC 4 d1 q3w until progressive disease or for a max. of 6 cycles
Other Name: multiple generics in existence

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female patients with pretreated epithelial ovarian cancer, primary peritoneal carcinomatosis or fallopian tube cancer with histological confirmation of the tumor
  • Wild-type k-ras status
  • Patients must have pretreated platinum-sensitive ovarian cancer with recurrence more than 6 months after completion of a platinum-containing regimen
  • Presence of at least one measurable or non-measurable disease (e.g. malignant ascites) following RECIST criteria by radiologic evaluation OR histological confirmation of recurrence by biopsy. The presence of non-measurable lesions only requires in addition a 2-fold increase of CA-125 elevation above normal lab value (confirmed by two measurements).
  • No more than 2 prior treatment regimens for these epithelial cancers
  • Age > 18 years.
  • ECOG Performance Status of 0 or 1
  • Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:

    • Hemoglobin > 9.0 g/dl
    • Leukocyte count >3.000/mm3 ; absolute neutrophil count (ANC) >1.500/mm3
    • Platelet count ≥ 100.000/μl
    • Total bilirubin < 1,0 times the upper limit of normal
    • ALT and AST < 2,5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer)
    • Alkaline phosphatase < 4 x ULN
    • PT-INR/PTT < 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.]
    • Serum creatinine < 1.5 x upper limit of normal and creatinine clearance > 50 ml/min.
    • Magnesium ≥ lower limit of normal; calcium ≥ lower limit of normal
  • Signed and dated informed consent before the start of specific protocol procedures.

Exclusion Criteria:

  • Clinically significant cardiovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrolment.
  • History of interstitial lung disease, e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.
  • History of HIV infection or chronic hepatitis B or C
  • Active clinically serious infections (> grade 2 NCI-CTC version 3.0)
  • Pre-existing neuropathy > grade 1 (NCI CTCAE), except for loss of tendon reflex
  • Prior radiological or clinical evidence of CNS metastases including previously treated, resected, or asymptomatic brain lesions or leptomeningeal involvement by head CT scan or MRI
  • Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
  • History of organ allograft
  • Patients with evidence or history of bleeding diathesis
  • Patients undergoing renal dialysis
  • Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry.
  • Patients in a closed institution according to an authority or court decision
  • Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study

Excluded therapies and medications, previous and concomitant:

  • Anticancer chemotherapy within 4 weeks prior to study entry.
  • Prior anti-EGFR therapy
  • Radiotherapy during study or within 4 weeks of start of study drug. (Palliative radiotherapy of non-target lesions will be allowed) and prior radiotherapy of > 25% of the bone marrow
  • Major surgery within 4 weeks of start of study
  • Autologous bone marrow transplant or stem cell rescue within 12 months of study
  • Investigational drug therapy outside of this trial during or within 4 weeks of study entry
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01388621

Contacts
Contact: Nadine Albers 0351-25933-281 nadine.albers@gmiho.de

Locations
Germany
Stauferklinikum Schwäbisch Gmünd Recruiting
Mutlangen, Baden Württemberg, Germany, 73557
Principal Investigator: Ekkehard von Abel, Dr. med         
Praxis Dr. Oettle Recruiting
Friedrichshafen, Baden-Württemberg, Germany, 88045
Principal Investigator: Helmut Oettle, MD (PD Dr. med.)         
Carl-Thiem-Klinikum Cottbus Frauenklinik Recruiting
Cottbus, Brandenburg, Germany, 03048
Principal Investigator: Andrzej Popiela, MD (Dr. med.)         
Praxis Dr. Heinrich Recruiting
Fuerstenwalde, Brandenburg, Germany, 15517
Principal Investigator: Georg Heinrich, MD (Dr. med.)         
Universitätsfrauenklinik am Klinikum Südstadt Withdrawn
Rostock, mecklenburg-Vorpommern, Germany, 18059
MVM mbH Onkologische Schwerpunktpraxis Leer Recruiting
Leer, Niedersachsen, Germany, 26789
Principal Investigator: Lothar Müller, MD (Dr. med.)         
Medizinisches Zentrum Bonn-Friedensplatz Recruiting
Bonn, Nordrhein-Westfalen, Germany, 53111
Principal Investigator: Christian M Kurbacher, MD (PD Dr. med.)         
Martin-Luther-Universität Halle-Wittenberg Zentrum für Frauenheilkunde und Geburtshilfe Recruiting
Halle, Sachsen-Anhalt, Germany, 06120
Principal Investigator: Hans-Georg Strauss, MD (Dr. med.)         
Klinikum Magdeburg Recruiting
Magdeburg, Sachsen-Anhalt, Germany, 39130
Principal Investigator: Christoph Kahl, MD (PD Dr. med.)         
Klinikum Chemnitz Frauen- und Kinderklinik Recruiting
Chemnitz, Sachsen, Germany, 09116
Principal Investigator: Petra Krabisch, MD (Dr. med.)         
Gynäkologische Praxis Dr. med. Ruhmland Recruiting
Berlin, Germany, 12683
Principal Investigator: Birgit Ruhmland, MD (Dr.)         
Helios Klinikum Berlin - Buch Withdrawn
Berlin, Germany, 13125
Praxisklinik Frauenheilkunde Recruiting
Berlin, Germany, 10367
Principal Investigator: Peter Klare, MD (Dr. med.)         
Ev. Waldkrankenhaus Spandau Recruiting
Berlin, Germany, 13589
Principal Investigator: Jochem Potenberg, MD (Dr. med)         
Frauenklinik Charité - Universitätsmedizin Berlin Campus Virchow-Klinikum Recruiting
Berlin, Germany, 13353
Principal Investigator: Jalid Sehouli, MD (Prof. Dr. med.)         
Park-Klinik Weißensee Recruiting
Berlin, Germany, 13086
Principal Investigator: Elke Keil, MD (Dr.)         
Praxis Dr. Schilling / Till / Kohn FÄ f. Gynäkologie u. Geburtshilfe, Gynäkol.-Onkol. Schwerpunktpraxis Recruiting
Berlin, Germany, 10317
Principal Investigator: Jörg Schilling, MD (Dr.)         
Tagesklinik Altonaer Strasse Recruiting
Hamburg, Germany, 20357
Principal Investigator: Andreas Nugent, MD (Dr. med.)         
Sponsors and Collaborators
WiSP Wissenschaftlicher Service Pharma GmbH
ClinAssess GmbH
Investigators
Principal Investigator: Jalid Sehouli, MD (Prof. Dr. med.) Frauenklinik Charité - Universitätsmedizin Berlin Campus Virchow-Klinikum
  More Information

No publications provided

Responsible Party: WiSP Wissenschaftlicher Service Pharma GmbH
ClinicalTrials.gov Identifier: NCT01388621     History of Changes
Other Study ID Numbers: GMIHO-008/2009_AG56, 2010-018849-59
Study First Received: May 17, 2011
Last Updated: August 19, 2013
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by WiSP Wissenschaftlicher Service Pharma GmbH:
ovarian cancer
fallopian cancer
recurrent
platinum-sensitive
KRAS-Wildtype

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Gemcitabine
Doxorubicin
Liposomal doxorubicin
Carboplatin
Antibodies, Monoclonal
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on September 16, 2014