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

Ovarian Cancer Clinical Trial

— PROVE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01388621
• Other study ID #: GMIHO-008/2009_AG56
• Secondary ID: 2010-018849-59
• Status: Recruiting
• Phase: Phase 2
• First received: May 17, 2011
• Last updated: August 19, 2013
• Start date: October 2011
• Est. completion date: July 2015

Study information

• Verified date: August 2013
• Source: WiSP Wissenschaftlicher Service Pharma GmbH
• Contact: Nadine Albers
• Phone: 0351-25933-281
• Email: nadine.albers[@]gmiho.de
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: July 2015
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Cancer
• Ovarian Neoplasms

Intervention

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.
• pegylated liposomal doxorubicin (PLD)
pegylated liposomal doxorubicin (PLD) 30 mg/m² d1 q4w until progressive disease or for a max. of 6 cycles
• Carboplatin
Carboplatin AUC 5 d1 q4w until progressive disease or for a max. of 6 cycles
• Gemcitabine
gemcitabine 1000 mg/m² d1 + 8 q3w until progressive disease or for a max. of 6 cycles
• Carboplatin
Carboplatin AUC 4 d1 q3w until progressive disease or for a max. of 6 cycles
• 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.

Locations

Country	Name	City	State
Germany	Ev. Waldkrankenhaus Spandau	Berlin
Germany	Frauenklinik Charité - Universitätsmedizin Berlin Campus Virchow-Klinikum	Berlin
Germany	Gynäkologische Praxis Dr. med. Ruhmland	Berlin
Germany	Helios Klinikum Berlin - Buch	Berlin
Germany	Park-Klinik Weißensee	Berlin
Germany	Praxis Dr. Schilling / Till / Kohn FÄ f. Gynäkologie u. Geburtshilfe, Gynäkol.-Onkol. Schwerpunktpraxis	Berlin
Germany	Praxisklinik Frauenheilkunde	Berlin
Germany	Medizinisches Zentrum Bonn-Friedensplatz	Bonn	Nordrhein-Westfalen
Germany	Klinikum Chemnitz Frauen- und Kinderklinik	Chemnitz	Sachsen
Germany	Carl-Thiem-Klinikum Cottbus Frauenklinik	Cottbus	Brandenburg
Germany	Praxis Dr. Oettle	Friedrichshafen	Baden-Württemberg
Germany	Praxis Dr. Heinrich	Fuerstenwalde	Brandenburg
Germany	Martin-Luther-Universität Halle-Wittenberg Zentrum für Frauenheilkunde und Geburtshilfe	Halle	Sachsen-Anhalt
Germany	Tagesklinik Altonaer Strasse	Hamburg
Germany	MVM mbH Onkologische Schwerpunktpraxis Leer	Leer	Niedersachsen
Germany	Klinikum Magdeburg	Magdeburg	Sachsen-Anhalt
Germany	Stauferklinikum Schwäbisch Gmünd	Mutlangen	Baden Württemberg
Germany	Universitätsfrauenklinik am Klinikum Südstadt	Rostock	mecklenburg-Vorpommern

Sponsors (2)

Lead Sponsor	Collaborator
WiSP Wissenschaftlicher Service Pharma GmbH	ClinAssess GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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)	No
Secondary	Progression-free survival		End of Follow-up (up to 1 year)	No
Secondary	Overall survival		End of Follow-up (up to 1 year)	No
Secondary	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)	Yes
Secondary	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)	No