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

WiSP Wissenschaftlicher Service Pharma

Status and phase: Unknown; Phase 2

Conditions: Ovarian Cancer

Treatments: Drug: Panitumumab; Drug: Carboplatin; Drug: pegylated liposomal doxorubicin (PLD); Drug: Gemcitabine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01388621

2010-018849-59 (EudraCT Number)

GMIHO-008/2009_AG56

Details and patient eligibility

About

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.

Enrollment: 140 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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140 participants in 2 patient groups

Experimental arm (A):

Experimental group

Description:

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.

Treatment:

Drug: Gemcitabine

Drug: Panitumumab

Drug: Carboplatin

Drug: Carboplatin

Drug: pegylated liposomal doxorubicin (PLD)

Drug: Panitumumab

Standard arm (B):

Active Comparator group

Description:

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.

Treatment:

Drug: Gemcitabine

Drug: Carboplatin

Drug: Carboplatin

Drug: pegylated liposomal doxorubicin (PLD)