This is an open label, multicenter, non-comparative, phase IV study of panitumumab
monotherapy in Indian subjects with previously treated, wild-type Kirsten rat sarcoma viral
oncogene homolog (KRAS) and wild-type Neuroblastoma rat sarcoma viral (v-ras) oncogene
homolog (NRAS), metastatic colorectal cancer. This study is designed to fulfil the
requirement of the Indian regulatory authority to characterize the safety and tolerability of
panitumumab when administered to Indian subjects with wild-type KRAS and wild-type NRAS
metastatic colorectal cancer. Approximately 58 Indian subjects with previously treated
wild-type KRAS and wild-type NRAS, metastatic colorectal cancer will be enrolled in order to
achieve the target enrollment of 50 evaluable subjects who have received at least one dose of
panitumumab. Subjects will receive panitumumab 6 milligram/kilogram (mg/kg) intravenously
every 14 days until disease progression, intolerability, withdrawal of consent, or death. All
subjects will be followed at 4 weeks and 8 weeks after the last administration of
panitumumab, unless the treatment was discontinued due to withdrawal of consent or death of
the subject.
All adverse events occurring from signing of informed consent form until 8 weeks after last
dose of panitumumab will be recorded. All Serious Adverse Events (SAE) considered related to
panitumumab by the investigator or the sponsor will be followed until the event resolves, or
is considered stable or until the subject is lost to follow-up or withdraws consent.
Inclusion Criteria:
- Subject or subject's legally acceptable representative has provided informed consent.
- Male or female >=18 years of age.
- Histologically or cytologically confirmed diagnosis of adenocarcinoma of the colon or
rectum.
Metastatic disease.
- Wild-type KRAS (without mutation in exon 2 [codons 12 and 13], exon 3 [codons 59 and
61], and exon 4 [codons 117 and 146]) and wild-type NRAS (without mutation in exon 2
[codons 12 and 13], exon 3 [codons 59 and 61], and exon 4 [codons 117 and 146]) tumor
status.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
- Measurable or non-measurable disease per RECIST Version 1.1.
- Must have failed after fluoropyrimidine-, oxaliplatin-, and irinotecan-containing
chemotherapy regimens for metastatic disease. Failure is defined as either disease
progression (clinical or radiological) or intolerance to the regimen. Metastatic
relapse within 6 months after completing adjuvant chemotherapy (with either an
irinotecan or oxaliplatin containing regimen) will also be considered as treatment
failure of a prior regimen for metastatic disease. Laboratory: Adequate baseline organ
function defined by (<=7 days prior to first dose of study treatment).
- Hematologic function, as follows: Absolute neutrophil count (ANC) >=1.5 x 10^9/Liter
(L), Platelet count >=75 x 10^9/L, Hemoglobin >=8.0 gram/deciliter (g/dL).
- Renal function, as follows: Creatinine <=1.5 x upper limit of normal (ULN).
- Hepatic function, as follows: Aspartate aminotransferase (AST) <=3 x ULN, Alanine
aminotransferase (ALT) <=3 x ULN, Total Bilirubin <=1.5 x ULN.
- Metabolic function, as follows: Serum Magnesium within normal limits. Serum Calcium
within normal limits. Serum Potassium within normal limits.
- All prior treatment related toxicities common terminology criteria for adverse events
(CTCAE) version 4.03 <=Grade 1 at the time of enrollment.
- Women of childbearing potential must have a negative serum pregnancy test within 7
days of first dose of study treatment and agree to use adequate contraception, during
the study and for 2 months following the last dose of study treatment. Men with a
female partner of childbearing potential must have either had a prior vasectomy or
agree to use adequate contraception, from time of signing informed consent until 5
months after the last dose of study treatment.
Exclusion Criteria:
- History or known presence of central nervous system metastases.
- History of another malignancy except: Malignancy treated with curative intent and with
no known active disease present for >=5 years prior to enrolment and felt to be at low
risk for recurrence by the treating physician; Adequately treated non-melanomatous
skin cancer or lentigo maligna without evidence of disease; Adequately treated
cervical carcinoma in situ without evidence of disease; Prostatic intraepithelial
neoplasia without evidence of prostate cancer.
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to panitumumab or excipients that contraindicates their
participation.
- Prior anti-epidermal growth factor receptor (EGFr) antibody therapy (e.g., panitumumab
or cetuximab) or treatment with small molecule EGFr inhibitors (e.g., gefitinib,
erlotinib, lapatinib).
- Antitumor therapy (e.g., chemotherapy, hormonal therapy, immunotherapy, antibody
therapy, radiotherapy), or investigational agent or therapy <=30 days before first
dose of study treatment or not recovered from any acute toxicity.
- Other investigational procedure <=30 days before study entry.
- History of interstitial lung disease (ILD) e.g., interstitial pneumonitis, pulmonary
fibrosis or evidence of ILD on baseline chest computer tomography.
- Subject previously enrolled to this study.
- History of keratitis, ulcerative keratitis or severe dry eye.
- Major surgery (e.g., requiring general anesthesia) <=30 days before first dose of
study treatment. Subjects must have recovered from any surgery related toxicities.
- Minor surgical procedure (e.g., open biopsy) <=7 days before first dose of study
treatment, or not yet recovered from prior minor surgery Note: uncomplicated placement
of vascular access device, fine needle aspiration, thoracocentesis or paracentesis >=3
days prior to first dose of study treatment is acceptable.
- Clinically significant cardiovascular disease (including myocardial infarction,
unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac
arrhythmia) <=6 months prior to enrolment.
- History of any medical or psychiatric condition or laboratory abnormality that in the
opinion of the investigator may increase the risk associated with the study
participation or investigational product administration, compliance with the study
procedures or may interfere with the interpretation of the results.
- Unstable pulmonary embolism, deep vein thrombosis, or other significant
arterial/venous thromboembolic event <=30 days before first dose of study treatment.
If on anticoagulation, subject must be on stable therapeutic dose prior to first dose
of study treatment.
- Subject who is pregnant or breast feeding, or planning to become pregnant during
treatment and within 2 months after the discontinuation of study treatment.
- Known positive test(s) for human immunodeficiency virus infection (testing is not
required in the absence of clinical suspicion).
- Active infection requiring systemic treatment or any uncontrolled infection <=14 days
prior to first dose of study treatment (with the exception of uncomplicated urinary
tract infection or upper respiratory tract infection).
- Subject has any kind of disorder that compromises the ability of the subject to give
written informed consent and/or to comply with study procedures or is unwilling or
unable to comply with study requirements.
