Clinical trial NCT01388621: Carboplatin-based Chemotherapy With or Without Panitumumab in Platinum-sensitive Recurrent Ovarian Cancer
Official title: PROVE A Randomized Phase II Trial of Standard Carboplatin-based Chemotherapy With or Without Panitumumab in Platinum-sensitive Recurrent Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: ovarian cancer
fallopian cancer
recurrent
platinum-sensitive
KRAS-Wildtype
Lead sponsor: WiSP Wissenschaftlicher Service Pharma GmbH
Sponsor class: OTHER
Collaborators: name: ClinAssess GmbH
First posted: 2011-07-06
Enrollment: 140
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Progression-free survival (PFS) rate after 12 months.
timeFrame: 12 month
Secondary outcomes:
measure: Duration of Tumor-Response
timeFrame: Duration of Therapy (Therapy is planned for 6 cycles of 3 resp. 4 weeks each, shorter or longer durations are possible)
measure: Progression-free survival
timeFrame: End of Follow-up (up to 1 year)
measure: Overall survival
timeFrame: End of Follow-up (up to 1 year)
measure: Maximum toxicity resp. AE grade per patient per toxicity resp. AE during therapy
timeFrame: Duration of Therapy (Therapy is planned for 6 cycles of 3 resp. 4 weeks each, shorter or longer durations are possible)
measure: Tumor Response Rate
timeFrame: Duration of Therapy (Therapy is planned for 6 cycles of 3 resp. 4 weeks each, shorter or longer durations are possible)
Other outcomes:
Locations:
city: Mutlangen
country: Germany
facility: Stauferklinikum Schwäbisch Gmünd
state: Baden Württemberg
city: Friedrichshafen
country: Germany
facility: Praxis Dr. Oettle
state: Baden-Württemberg
city: Cottbus
country: Germany
facility: Carl-Thiem-Klinikum Cottbus Frauenklinik
state: Brandenburg
city: Fuerstenwalde
country: Germany
facility: Praxis Dr. Heinrich
state: Brandenburg
city: Rostock
country: Germany
facility: Universitätsfrauenklinik am Klinikum Südstadt
state: mecklenburg-Vorpommern
city: Leer
country: Germany
facility: MVM mbH Onkologische Schwerpunktpraxis Leer
state: Niedersachsen
city: Bonn
country: Germany
facility: Medizinisches Zentrum Bonn-Friedensplatz
state: Nordrhein-Westfalen
city: Halle
country: Germany
facility: Martin-Luther-Universität Halle-Wittenberg Zentrum für Frauenheilkunde und Geburtshilfe
state: Sachsen-Anhalt
city: Magdeburg
country: Germany
facility: Klinikum Magdeburg
state: Sachsen-Anhalt
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz Frauen- und Kinderklinik
state: Sachsen
city: Berlin
country: Germany
facility: Praxis Dr. Schilling / Till / Kohn FÄ f. Gynäkologie u. Geburtshilfe, Gynäkol.-Onkol. Schwerpunktpraxis
city: Berlin
country: Germany
facility: Praxisklinik Frauenheilkunde
city: Berlin
country: Germany
facility: Gynäkologische Praxis Dr. med. Ruhmland
city: Berlin
country: Germany
facility: Park-Klinik Weißensee
city: Berlin
country: Germany
facility: Helios Klinikum Berlin - Buch
city: Berlin
country: Germany
facility: Frauenklinik Charité - Universitätsmedizin Berlin Campus Virchow-Klinikum
city: Berlin
country: Germany
facility: Ev. Waldkrankenhaus Spandau
city: Hamburg
country: Germany
facility: Tagesklinik Altonaer Strasse
Study officials:
affiliation: Frauenklinik Charité - Universitätsmedizin Berlin Campus Virchow-Klinikum
name: Jalid Sehouli, MD (Prof. Dr. med.)
role: PRINCIPAL_INVESTIGATOR
References: