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

Sponsor

WiSP Wissenschaftlicher Service Pharma GmbH (Other)

Overall Status

Unknown status

CT.gov ID

NCT01388621

Collaborator

ClinAssess GmbH (Industry)

140

Enrollment

Locations

Arms

Duration (Months)

7.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

140 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Oct 1, 2011

Anticipated Primary Completion Date :

Jul 1, 2014

Anticipated Study Completion Date :

Jul 1, 2015

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS) rate after 12 months. [12 month]
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 [Duration of Therapy (Therapy is planned for 6 cycles of 3 resp. 4 weeks each, shorter or longer durations are possible)]
according to RECIST, including measurable disease patients only, and including patients with CA-125 defined disease as well
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 [Duration of Therapy (Therapy is planned for 6 cycles of 3 resp. 4 weeks each, shorter or longer durations are possible)]
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 [Duration of Therapy (Therapy is planned for 6 cycles of 3 resp. 4 weeks each, shorter or longer durations are possible)]
according to RECIST, including measurable disease patients only, and including patients with CA-125 defined disease as well

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Stauferklinikum Schwäbisch Gmünd	Mutlangen	Baden Württemberg	Germany	73557
2	Praxis Dr. Oettle	Friedrichshafen	Baden-Württemberg	Germany	88045
3	Carl-Thiem-Klinikum Cottbus Frauenklinik	Cottbus	Brandenburg	Germany	03048
4	Praxis Dr. Heinrich	Fuerstenwalde	Brandenburg	Germany	15517
5	Universitätsfrauenklinik am Klinikum Südstadt	Rostock	mecklenburg-Vorpommern	Germany	18059
6	MVM mbH Onkologische Schwerpunktpraxis Leer	Leer	Niedersachsen	Germany	26789
7	Medizinisches Zentrum Bonn-Friedensplatz	Bonn	Nordrhein-Westfalen	Germany	53111
8	Martin-Luther-Universität Halle-Wittenberg Zentrum für Frauenheilkunde und Geburtshilfe	Halle	Sachsen-Anhalt	Germany	06120
9	Klinikum Magdeburg	Magdeburg	Sachsen-Anhalt	Germany	39130
10	Klinikum Chemnitz Frauen- und Kinderklinik	Chemnitz	Sachsen	Germany	09116
11	Praxis Dr. Schilling / Till / Kohn FÄ f. Gynäkologie u. Geburtshilfe, Gynäkol.-Onkol. Schwerpunktpraxis	Berlin		Germany	10317
12	Praxisklinik Frauenheilkunde	Berlin		Germany	10367
13	Gynäkologische Praxis Dr. med. Ruhmland	Berlin		Germany	12683
14	Park-Klinik Weißensee	Berlin		Germany	13086
15	Helios Klinikum Berlin - Buch	Berlin		Germany	13125
16	Frauenklinik Charité - Universitätsmedizin Berlin Campus Virchow-Klinikum	Berlin		Germany	13353
17	Ev. Waldkrankenhaus Spandau	Berlin		Germany	13589
18	Tagesklinik Altonaer Strasse	Hamburg		Germany	20357