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

PROVE A Randomized Phase II Trial of Standard Carboplatin-based Chemotherapy With or Without Panitumumab in Platinum-sensitive Recurrent Ovarian Cancer

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.

Study Overview

• Status: Unknown
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: Panitumumab; Drug: pegylated liposomal doxorubicin (PLD); Drug: Carboplatin; Drug: Gemcitabine; Drug: Carboplatin; Drug: Panitumumab

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Phase 2

Contacts and Locations

Study Locations

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    • Withdrawn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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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 Names: Caelyx; Drug: Carboplatin; Carboplatin AUC 5 d1 q4w until progressive disease or for a max. of 6 cycles; Other Names: multiple generics in existence; Drug: Gemcitabine; gemcitabine 1000 mg/m² d1 + 8 q3w until progressive disease or for a max. of 6 cycles; Other Names: Gemzar; Drug: Carboplatin; Carboplatin AUC 4 d1 q3w until progressive disease or for a max. of 6 cycles; Other Names: 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 Names: 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 Names: Caelyx; Drug: Carboplatin; Carboplatin AUC 5 d1 q4w until progressive disease or for a max. of 6 cycles; Other Names: multiple generics in existence; Drug: Gemcitabine; gemcitabine 1000 mg/m² d1 + 8 q3w until progressive disease or for a max. of 6 cycles; Other Names: Gemzar; Drug: Carboplatin; Carboplatin AUC 4 d1 q3w until progressive disease or for a max. of 6 cycles; Other Names: multiple generics in existence

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) rate after 12 months.	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).	12 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Tumor-Response	according to RECIST, including measurable disease patients only, and including patients with CA-125 defined disease as well	Duration of Therapy (Therapy is planned for 6 cycles of 3 resp. 4 weeks each, shorter or longer durations are possible)
Progression-free survival		End of Follow-up (up to 1 year)
Overall survival		End of Follow-up (up to 1 year)
Maximum toxicity resp. AE grade per patient per toxicity resp. AE during therapy	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.	Duration of Therapy (Therapy is planned for 6 cycles of 3 resp. 4 weeks each, shorter or longer durations are possible)
Tumor Response Rate	according to RECIST, including measurable disease patients only, and including patients with CA-125 defined disease as well	Duration of Therapy (Therapy is planned for 6 cycles of 3 resp. 4 weeks each, shorter or longer durations are possible)

Collaborators and Investigators

• Sponsor: WiSP Wissenschaftlicher Service Pharma GmbH
• Collaborators: ClinAssess GmbH
• Investigators: Principal Investigator: Jalid Sehouli, MD (Prof. Dr. med.), Frauenklinik Charité - Universitätsmedizin Berlin Campus Virchow-Klinikum

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Anticipated): July 1, 2014
• Study Completion (Anticipated): July 1, 2015

Study Registration Dates

• First Submitted: May 17, 2011
• First Submitted That Met QC Criteria: July 4, 2011
• First Posted (Estimate): July 6, 2011

Study Record Updates

• Last Update Posted (Estimate): August 20, 2013
• Last Update Submitted That Met QC Criteria: August 19, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: ovarian cancer; recurrent; platinum-sensitive; KRAS-Wildtype; fallopian cancer
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Hypersensitivity; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Gemcitabine; Carboplatin; Doxorubicin; Liposomal doxorubicin; Panitumumab
• Other Study ID Numbers: GMIHO-008/2009_AG56; 2010-018849-59 (EudraCT Number)