None listed
Conditions
Brief summary
This study aims to determine the feasibility of a personalised treatment strategy, on the basis of a tumour molecular signature via genomic sequencing and protein expression, in patients with advanced recurrent or metastatic pancreatic adenocarcinoma. Who is it for? You may be eligible to join this study if you are aged 18 years or above, with histologically confirmed primary adenocarcinoma of the pancreas, and have one of the following three molecular signatures: 1. HER2 positive (HER2/neu amplification) subgroup 2. Homologous recombinant defects (BRCA1/BRCA2 or PALB2 mutation) subgroup 3. antiEGFR responsive sub-group (KRAS wildtype or KRAS codon13 mutation) Study details Ten patients will be enrolled in a feasibility stage to determine the technical feasibility of enrolling patients to a personalised treatment approach (including the logistics of recruitment, delivery of personalised treatment and general trial conduct). Recruitment to the HER2 positive subgroup will be reviewed after 1 patient has received personalised treatment. Personalised treatment based on genetic signature will comprise of the following: 1. HER2 positive sub-group - gemcitabine 1000mg/m2 over 30 minutes, given intravenously on days 1, 8 & 15 every 28 days until progression or unacceptable toxicity plus trastuzumab 4mg/kg intravenously day 1 only, followed by trastuzumab 2mg/kg given intravenously day 8, then weekly every subsequent week until progression or unacceptable toxicity or a total of 6 months treatment is completed. 2. Homologous recombinant defects subgroup - gemcitabine 1000mg/m2 over 30 minutes, given intravenously on days 1, 8 & 15 every 28 days until progression or unacceptable toxicity plus cisplatin 50 mg/m2 given intravenously over 60 minutes on days 1& 15 every 28 days until progression or unacceptable toxicity 3. antiEGFR responsive sub-group - gemcitabine 1000mg/m2 given intravenously days 1,8 & 15 each 28 day cycle until progression or unacceptable toxicity plus erlotinib 100mg orally daily continuously until progression or unacceptable toxicity Note: Patients may have received up to one cycle of standard gemcitabine treatment or gemcitabine in combination with abraxane prior to personalised treatment Patients will be evaluated at least 4 weekly to see how they are responding to treatment until progression, unacceptable toxicity or a total of 6 months treatment is completed.
Interventions
Personalised Treatment (based on molecular phenotype):
1. HER2 positive sub-group - gemcitabine 1000mg/m2 over 30 minutes, given intravenously on days 1, 8 & 15 every 28 days until progression or unacceptable toxicity
plus
trastuzumab 4mg/kg intravenously day 1 only, followed by trastuzumab 2mg/kg given intravenously day 8, then weekly every subsequent week until progression or unacceptable toxicity or a total of 6 months treatment is completed.
2. Homologous recombinant defects subgroup - ge
Personalised Treatment (based on molecular phenotype): 1. HER2 positive sub-group - gemcitabine 1000mg/m2 over 30 minutes, given intravenously on days 1, 8 & 15 every 28 days until progression or unacceptable toxicity plus trastuzumab 4mg/kg intravenously day 1 only, followed by trastuzumab 2mg/kg given intravenously day 8, then weekly every subsequent week until progression or unacceptable toxicity or a total of 6 months treatment is completed. 2. Homologous recombinant defects subgroup - gemcitabine 1000mg/m2 over 30 minutes, given intravenously on days 1, 8 & 15 every 28 days until progression or unacceptable toxicity plus cisplatin 50 mg/m2 given intravenously over 60 minutes on days 1& 15 every 28 days until progression or unacceptable toxicity 3. antiEGFR responsive sub-group - gemcitabine 1000mg/m2 given intravenously days 1,8 & 15 each 28 day cycle until progression or unacceptable toxicity plus erlotinib 100mg orally daily continuously until progression or unacceptable toxicity
Sponsors
The Australasian Gastro-Intestinal Trials Group (AGITG)
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult males or females 18 years or over with histologically confirmed primary adenocarcinoma of the pancreas who have cytological confirmation of recurrent or metastatic disease 2. Are currently enrolled in APGI and have consented through APGI to notify them if something of significance in regards to their cancer is found. 3. One of the following specified three molecular signatures: *HER2 positive (HER2/neu over expression) subgroup; assessed using detailed DNA sequencing and RNA expression analysis and confirmed by HER2 ISH testing (using standard gastric cancer protocols). *Homologous recombinant defects (BRCA1/BRCA2 or PALB2 mutation*) subgroup; assessed using detailed DNA sequencing and confirmed by PCR. *antiEGFR responsive (KRAS WT or KRAS codon 13 mutation) subgroup; assessed using detailed DNA sequencing and confirmed by PCR (using standard colorectal cancer protocols). (* While variants of BRCA1, BRCA2 and PALB2 will be detected in the APGI study, only pathological mutations will be included in the homologous recombinant defects phenotype) 4. For HER2 positive patients adequate cardiac function, defined as Left Ventricular Ejection fraction (LVEF) which equals 50% or above the ULN for the institution (whichever is lower). Cardiac function should be assessed within 3 months prior to registration; 5. Have a life expectancy of over 3 months; 6. Performance status of ECOG 0- 2; 7. Patients must have measurable disease (per RECIST 1.1) or evaluable non-measureable disease when lesions below the limits defined for measurable disease by RECIST 1.1. The CT scan should be conducted within 2 weeks of planned treatment commencement. 8. Adequate bone marrow function with platelets which equal or are greater than 100 x 109/L, neutrophils which equal or are greater than 1.5 x 109/L and haemoglobin which equal or are greater than 9.0 g/dL; 9. Adequate renal function (with calculated creatinine clearance greater than 50 ml/min based on the Cockcroft-Gault method, 24hour urine or GFR scan) and serum creatinine which equal or is less than 1.5 x Upper Limit of Normal range (ULN); 10. Adequate hepatic function with serum total bilirubin which equal or are less than 1.5 x upper limit of normal range and ALT/AST which equal or are less than 2.5x upper limit of normal range (or less than 5.0 times ULN with documented liver metastases), alkaline phosphatase which equal or are less than 5x upper limit of normal range, and INR which equal or are less than 1.5; 11. No prior evidence of underlying abnormality in coagulation parameters. Patients who are therapeutically treated with heparin will be allowed to participate provided there are adequate coagulation parameters. Patients who are on warfarin will be allowed to participate provided they are on low molecular weight heparin prior to starting study treatment. 12. Study treatment both planned and able to start within 7 days of registration. If a PICC or portacath is required for treatment, an extra 7 days will be allowed to facilitate this. 13. Signed, written informed consent.
Exclusion criteria
1. Contraindications to any study treatments; 2. Prior systemic treatment for recurrent / metastatic disease except for patients with the HER2 positive or antiEGFR responsive target molecular signature. In patients with these molecular signatures, up to one cycle of standard dose gemcitabine +/- abraxane chemotherapy commenced within 5 weeks prior to registration to the study. (For patients receiving an initial cycle of gemcitabine +/- abraxane, they must be considered still suitable for ongoing chemotherapy at standard doses by their responsible clinician. 3. Patients who have received neoadjuvant or adjuvant chemotherapy with gemcitabine +/- abraxane, including chemoradiation, following surgical resection of pancreatic cancer and completed treatment within the last 6 months, unless further treatment with gemcitabine or abraxane is appropriate in the opinion of the treating clinician; 4. Untreated brain metastases or leptomeningeal disease. Patients with brain metastases that have been treated, and are asymptomatic, and have been stable for 3 or more months after treatment are allowed. A baseline CT brain or MRI is only required if there is clinical suspicion of central nervous system involvement; 5. History of another malignancy within 5 years prior to registration. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, curatively treated cervical carcinoma in situ or non-melanomatous carcinoma of the skin or superficial transitional cell carcinoma of the bladder are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 5 years after definitive primary treatment; 6. Any significant active infection, including chronic active hepatitis B, hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated. Patients with known Hepatitis B/C infection will be allowed to participate providing evidence of viral suppression has been documented and the patient remains on appropriate anti-viral therapy; 7. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol; 8. Pregnancy, lactation, or inadequate contraception. Women must be post menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 14 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception.
Outcome results
None listed