A Phase II clinical trial to compare the effectiveness of gemcitabine and nab-paclitaxel administered in combination with ATRA vs without ATRA in patients with locally advanced treatment-naïve pancreatic cancer
Trial ID: ISRCTN11503604
Other - Phase 2 - Recruiting
https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-of-atra-and-chemotherapy-for-pancreatic-cancer-starpac-2-or-primus-005
Background and study aims
Pancreatic cancer is a cancer that's found anywhere in the pancreas. The pancreas is an organ in the top part of your tummy. It helps you digest your food and makes hormones, such as insulin.
Pancreatic cancer (PDAC) is the fourth-highest cancer killer worldwide and is responsible for 6% of cancer deaths. Around 80% of patients are diagnosed at a late stage when cancer has spread and surgical removal is no longer possible. Most patients appear with advanced disease, with approximately 35% of patients having locally advanced (laPDAC), for which the current treatment options are minimally effective.
Who can participate?
Patients aged 16 years or above, with pancreatic cancer.
What does the study involve?
Patients will be randomised to receive gemcitabine + nab-paclitaxel or gemcitabine + nab-paclitaxel + ATRA. ATRA (if allocated), gemcitabine and nab-paclitaxel will be administered in 28-day cycles. ATRA will be administered for 6 cycles whereas gemcitabine/nab-paclitaxel will be administered until the disease worsens, and all patients will be followed up every 3 months via telephone or patient medical records until death, loss to follow-up, or study termination by the Sponsor, whichever occurs first. Eligible patients will be identified through Precision-Panc, a national initiative for pancreatic cancer funded by CRUK, or in the normal NHS setting when undergoing exploratory surgery for their pancreatic cancer.
What are the possible benefits and risks of participating?
This trial aims to find out information that may help people with locally advanced pancreatic cancer who have not had prior treatment for this disease. It cannot be guaranteed that there will be a benefit to participants during their treatment as this is unknown at this stage.
Participants may have side effects from the drugs or procedures carried out in this study and they will vary from person to person. Everyone taking part in the study will be followed carefully for any side effects through regular checks such as blood tests, vital signs, physical examinations and review of any illnesses or symptoms. Common side effects (though not an exhaustive list) include hair loss, nausea, vomiting, diarrhoea, low platelets in the blood, low white blood cells, nerve damage that can cause pain, numbness or weakness, lack of energy, body pains, fever, cough and abnormal liver function tests.
Where is the study run from?
St Bartholomew's Hospital (UK)
When is the study starting and how long is it expected to run for?
August 2019 to February 2029
Who is funding the study?
1. Medical Research Council (UK)
2. Celgene Corporation (USA)
Who is the main contact?
Professor Hemant Kocher, bci-starpac2@qmul.ac.uk
Conditions
- Pancreatic cancer
- Cancer
- Malignant neoplasms of digestive organs
Interventions
- Gemcitabine, nab-paclitaxel, ATRA
Eligibility
Inclusion criteria
- Current inclusion criteria as of 07/11/2024:
1. Written informed consent prior to admission to this study
2. Age ≥16 years. No upper age limit
3. ECOG performance status 0 or 1
4. Histologically proven pancreatic ductal adenocarcinoma (PDAC) as part of the Precision-Panc Master Protocol, or for patients who have undergone exploratory laparotomy and found to have locally advanced disease
5. Locally advanced disease which is measurable according to the Response Evaluation Criteria in Solid Tumours (RECIST v1.1)
6. CT chest abdomen and pelvis within 28 days as well as PET-CT within 42 days of randomisation (MRI Liver only if indeterminate liver lesions) to confirm absence of metastatic disease.
7. Received no prior systemic therapy for pancreatic cancer
8. Adequate haematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment:
8.1. Absolute Neutrophil Count ≥1.5 x 10^9/l (without granulocyte colony-stimulating factor support within 2 weeks prior to the first study treatment)
8.2. Platelet count ≥100 x 10^9/l (without transfusion within 2 weeks prior to the first study treatment)
8.3. Haemoglobin ≥10 g/dl (transfusion permitted to establish target haemoglobin levels prior to the first study treatment)
8.4. Calculated creatinine clearance (e.g. Cockcroft-Gault) ≥ 50 ml/min
8.5. Bilirubin level ≤1.5 ULN (patients with known Gilbert disease who have bilirubin levels ≤3 x ULN may be enrolled). Patients must be able to undergo biliary stenting if required before or, if required, during the trial
8.6. AST or ALT <2.5 x ULN
8.7. Alkaline phosphatase (ALP) <2.5 x ULN
8.8. INR and aPTT ≤1.5 x ULN this applies only to patients who are not receiving therapeutic anticoagulation patients receiving therapeutic anticoagulation should be on a stable dose
9. Female patients of child-bearing potential are eligible, provided they have a negative serum pregnancy test within 7 days prior to the first dose of study treatment, preferably as close to the first dose as possible. All patients with reproductive potential must agree to use a medically acceptable method of contraception throughout the treatment period and for 1 month after discontinuation of ATRA and/or gemcitabine/nab-paclitaxel (whichever is the latest) and for 6 months after discontinuation for male patients. Acceptable methods of contraception include IUD, oral contraceptive, sub-dermal implant and double barrier (condom with a contraceptive sponge or contraceptive pessary). Micro-dosed progesterone preparations (“mini-pill”) are an inadequate method of contraception during treatment with ATRA. If patients are taking this pill they should be instructed to stop and another form of contraceptive should be prescribed instead
10. Able to follow protocol requirements as assessed by the Principal Investigator
Previous inclusion criteria:
1. Written informed consent prior to admission to this study
2. Age ≥16 years. No upper age limit
3. ECOG performance status 0 or 1
4. Histologically proven pancreatic ductal adenocarcinoma (PDAC) as part of the Precision-Panc Master Protocol, or for patients who have undergone exploratory laparotomy and found to have locally advanced disease
5. Locally advanced disease which is measurable according to the Response Evaluation Criteria in Solid Tumours (RECIST v1.1)
6. CT chest abdomen and pelvis as well as PET-CT within 28 days of day 1 of treatment (MRI Liver only if indeterminate liver lesions) to confirm absence of metastatic disease.
7. Received no prior systemic therapy for pancreatic cancer
8. Adequate haematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment:
8.1. Absolute Neutrophil Count ≥1.5 x 10^9/l (without granulocyte colony-stimulating factor support within 2 weeks prior to the first study treatment)
8.2. Platelet count ≥100 x 10^9/l (without transfusion within 2 weeks prior to the first study treatment)
8.3. Haemoglobin ≥10 g/dl (transfusion permitted to establish target haemoglobin levels prior to the first study treatment)
8.4. Calculated creatinine clearance (e.g. Cockcroft-Gault) ≥ 50 ml/min
8.5. Bilirubin level ≤1.5 ULN (patients with known Gilbert disease who have bilirubin levels ≤3 x ULN may be enrolled). Patients must be able to undergo biliary stenting if required before or, if required, during the trial
8.6. AST or ALT <2.5 x ULN
8.7. Alkaline phosphatase (ALP) <2.5 x ULN
8.8. INR and aPTT ≤1.5 x ULN this applies only to patients who are not receiving therapeutic anticoagulation patients receiving therapeutic anticoagulation should be on a stable dose
9. Female patients of child-bearing potential are eligible, provided they have a negative serum pregnancy test within 7 days prior to the first dose of study treatment, preferably as close to the first dose as possible. All patients with reproductive potential must agree to use a medically acceptable method of contraception throughout the treatment period and for 1 month after discontinuation of ATRA and/or gemcitabine/nab-paclitaxel (whichever is the latest) and for 6 months after discontinuation for male patients. Acceptable methods of contraception include IUD, oral contraceptive, sub-dermal implant and double barrier (condom with a contraceptive sponge or contraceptive pessary). Micro-dosed progesterone preparations (“mini-pill”) are an inadequate method of contraception during treatment with ATRA. If patients are taking this pill they should be instructed to stop and another form of contraceptive should be prescribed instead
10. Able to follow protocol requirements as assessed by the Principal Investigator
Exclusion criteria
- 1. Patient has known metastases
2. Patient has experienced a significant reduction in performance status between the screening/ baseline visit and within 72 hours prior to commencement of treatment as per trial protocol, and as per the Investigator’s assessment
3. Patients with pre-existing sensory neuropathy >grade 1
4. History of other malignancies (except cured basal or squamous cell carcinoma, superficial bladder cancer, prostate cancer in active surveillance, or carcinoma in situ of the cervix) unless documented free of cancer for ≥2 years
5. Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
6. Patient has known active, uncontrolled HIV, or active, uncontrolled hepatitis B or C infection. Patients with undetectable viral load are eligible
7. Patient has undergone major surgery, other than diagnostic surgery (i.e. surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study
8. Patient has a history of allergy (including soya bean or peanut allergies) or hypersensitivity to any of the study drugs or any of their excipients, or the patient exhibits any of the events outlined in the Contraindications or Special Warnings and Precautions sections of the products or comparator SmPC or Prescribing Information
9. History of connective tissue disorders (e.g., lupus, scleroderma, arteritis nodosa)
10. Patient with a history of interstitial lung disease, history of slowly progressive dyspnoea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies
11. Patient with high cardiovascular risk, including, but not limited to, recent coronary stenting or myocardial infarction in the past year. A high cardiovascular risk is defined as person having recent (within last 12 months) coronary stenting or myocardial infarction or unstable angina which in the opinion of Principal Investigator, with or without a cardiologist opinion, is deemed to have an absolute risk for cardiovascular death of ≥ 5% over next 10 years. (ESC/ESH guidelines)
12. History of Peripheral Artery Disease (e.g., claudication, Leo-Buerger's disease)
13. Patient has serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, which could compromise the patient's safety or the study data integrity
14. Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug ≤30 days prior to study entry depending on the half-life of the investigational drug and/or guidance issued by the IMP manufacturer. Please contact the STARPAC2 coordinating team for further information
15. Patient is taking any prohibited concurrent medication, including vitamin A supplements, and is unwilling to stop use prior to and during the trial
16. Patient is pregnant, planning to become pregnant or breast feeding
17. Patient has received a live vaccine within four weeks prior to receiving their first dose of study treatment
18. Patient is unwilling or unable to comply with study procedures, as assessed by the Principal Investigator
Sponsor
Queen Mary University of London
Source: https://www.isrctn.com/
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