Phase 2 Pancreatic Cancer Trial, Recruiting

Written by an AI model from ClinicalTrials.gov eligibility criteria and checked on a sample basis. Please confirm against the original criteria.

Who might be able to join this trial:

General requirements (all modules):

• People whose cancer is currently progressing at the time of enrolment
• People who are well enough to carry out daily activities, with no worsening in the two weeks before enrolment (as measured by a standard performance scale)
• People whose kidneys, liver, and bone marrow are functioning well enough to safely receive treatment

Module 1 – Part A (PARP inhibitor dose finding):

• People with confirmed relapsed advanced ovarian, fallopian tube, or primary peritoneal cancer who have a specific genetic mutation in one of the following DNA repair genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D
• People with confirmed HER2-negative breast cancer that has come back or spread, with a mutation in one of the same DNA repair genes listed above
• People with confirmed advanced or metastatic prostate cancer that no longer responds to hormone treatment, with a mutation in one of the same DNA repair genes
• People with confirmed advanced or metastatic pancreatic cancer with a mutation in one of the same DNA repair genes
• People whose cancer can be detected and measured on scans
• People who are considered suitable for treatment with a PARP inhibitor (a type of targeted cancer drug)
• People who are able to eat a high-fat meal and follow fasting instructions as required

Module 1 – Part B (breast cancer dose expansion):

• People with confirmed HER2-negative breast cancer that has spread or come back locally, with a relevant gene mutation in the DNA repair genes listed above
• People who have at least one area of cancer that has not been previously treated with radiotherapy and measures at least 10mm
• People who previously received platinum-based chemotherapy for advanced breast cancer, provided their cancer did not progress during that treatment
• People who received platinum-based chemotherapy before or after surgery, provided at least 12 months have passed since the last dose

Module 2 – Brain tumour (glioma):

• People with a type of brain tumour called IDH1/2-mutant glioma who are considered suitable for a chemotherapy called temozolomide (TMZ)
• People whose brain tumour has come back after previous radiotherapy and one prior course of chemotherapy that works by damaging DNA (called alkylating chemotherapy)
• People whose returning tumour can be seen on an MRI scan
• Women who could become pregnant must have a negative pregnancy test before starting and before each treatment cycle

Module 3 – Panel 1 (solid tumours with PARP inhibitor):

• People who agree to provide blood samples and tumour tissue for testing at a central laboratory
• People with one of the following confirmed cancers and a relevant gene mutation (BRCA1, BRCA2, PALB2, RAD51C, or RAD51D): HER2-negative breast cancer that has spread or come back; relapsed advanced ovarian, fallopian tube, or primary peritoneal cancer; advanced or metastatic castration-resistant prostate cancer; or advanced or metastatic pancreatic cancer
• People whose cancer can be detected on scans (measurable or non-measurable areas of disease)
• People whose cancer has stopped responding to standard treatments, or for whom no standard treatment exists
• A small number of participants (up to 2) may be included if they have brain metastases (cancer that has spread to the brain) that are either previously treated or untreated but do not need immediate local treatment, and have had stable neurological function for at least 14 days

Module 3 – Panel 2 (brain tumour with glioma):

• People with IDH1/2-mutant glioma who are suitable for TMZ chemotherapy
• People whose glioma has come back after radiotherapy and one prior course of alkylating chemotherapy
• People whose returning tumour can be seen on MRI and has at least one tumour area larger than 1cm
• People who have a stored tumour tissue sample available for central laboratory testing
• People whose organ and bone marrow function is adequate without needing blood transfusions or growth factor support in the 14 days before enrolment

Module 3 – Panel 3 (HER2-negative breast cancer):

• People who agree to provide blood samples and tumour tissue for central laboratory testing
• People with confirmed HER2-negative breast cancer that has come back or spread, with a relevant gene mutation in BRCA1, BRCA2, PALB2, RAD51C, or RAD51D
• People whose cancer can be detected on scans
• People whose cancer has stopped responding to standard treatments, or for whom no standard treatment exists

Module 4 – Part A (HER2-positive and other tumour types):

• People with breast cancer, non-small cell lung cancer, colorectal cancer, bladder cancer, ovarian cancer, gastric cancer, or certain other cancers (including biliary tract, cervical, endometrial, or pancreatic cancer) that cannot be removed by surgery or have spread, and whose tumour tests positive for a protein called HER2 at a level specified for each cancer type (confirm with trial site)
• People with non-small cell lung cancer who have a specific change (activating mutation) in the HER2 gene
• People whose cancer has progressed after at least one, but no more than two, prior courses of chemotherapy for advanced or metastatic disease, and for whom no satisfactory alternative treatment exists
• People with a heart pumping function (LVEF) of 50% or above, measured within 28 days before starting treatment
• People who have at least one area of cancer that has not previously been treated with radiotherapy (or has shown progression after radiotherapy)
• Men who are sexually active with a female partner who could become pregnant must use a condom with spermicide from screening until approximately 6 months after their last dose
• Men must not father a child or donate sperm during the study and for approximately 6 months after their last dose

Module 4 – Part B (HER2-low or HER2-ultralow breast cancer, dose expansion):

• People with confirmed unresectable (cannot be removed by surgery) or metastatic breast cancer with HER2-low or HER2-ultralow status
• People who have not previously received chemotherapy for locally advanced unresectable or metastatic breast cancer
• People with brain metastases who have had stable neurological function for at least 14 days, and whose steroid dose (if applicable) has been stable or reducing for at least 14 days (confirm with trial site)
• People in the brain metastasis cohort who have untreated, or previously treated but stable or progressing brain metastases that do not need immediate local treatment

Module 5 (TROP2-directed treatment for select solid tumours):

• People with triple-negative breast cancer (TNBC), endometrial cancer, ovarian cancer, or castration-resistant prostate cancer that cannot be surgically removed or has spread
• People whose cancer has progressed after at least one prior systemic treatment and for whom no satisfactory alternative treatment exists
• People who have at least one area of cancer, not previously treated with radiotherapy, that measures at least 10mm
• Men who are sexually active with a female partner who could become pregnant must use a condom with spermicide from screening until approximately 4 months after their last dose
• Men must not father a child or donate sperm during the study and for approximately 4 months after their last dose

Reproductive requirements (Modules 1, 2 and 3):

• Women who could become pregnant must have a negative pregnancy test at screening and before each treatment cycle, and must use at least one highly effective contraceptive method plus a barrier method from screening until approximately 6 months after the last dose
• Women must not breastfeed and must not donate or retrieve eggs from screening until approximately 6 months after the last dose
• Men who are not surgically sterilised and are sexually active with a female partner who could become pregnant must use a condom with spermicide from screening until approximately 3 months after the last dose
• Men must not father a child or donate sperm from the start of treatment until approximately 3 months after the last dose

Reproductive requirements (Modules 4 and 5):

• Women who could become pregnant must have a negative pregnancy test at screening and before each cycle, and must use at least one highly effective contraceptive method combined with a condom and spermicide from screening until approximately 7 months after the last dose
• Women must not breastfeed and must not donate or retrieve eggs from screening until approximately 7 months after the last dose

Who may not be able to join:

General exclusions (all modules):

• People who have had major surgery within 4 weeks before the first treatment dose
• People who have had wide-field radiotherapy within 4 weeks, or limited palliative radiotherapy within 2 weeks, before the first treatment dose
• People who still have significant side effects from previous cancer treatments (above a mild level, with the exception of hair loss)
• People with a history of persistently very low blood counts (affecting red blood cells, white blood cells, and platelets) for any reason
• People with spinal cord compression, unless it has been treated, is stable, and does not require ongoing steroid treatment above a low dose for at least 4 weeks before starting
• People with a history of uncontrolled seizures, a need to take more than two anti-seizure medicines at the same time, or any history of epilepsy or seizures unrelated to the tumour
• People with a history of severe brain injury or stroke
• People with serious uncontrolled illness, including active bleeding conditions, or active infections including hepatitis B, hepatitis C, or HIV
• People with serious uncontrolled illness that has been active within the last 12 months
• People with a known tendency to bleed
• People with a blood cancer condition called myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML), or features suggesting these conditions
• People with severe nausea or vomiting that cannot be controlled, chronic gut diseases, inability to swallow the study drug, or a history of major bowel surgery that would prevent the drug from being properly absorbed
• People with a known allergy or sensitivity to the study drug or any of its ingredients
• People who cannot have gadolinium-enhanced MRI scans (a type of detailed scan using a contrast dye), or who cannot maintain a stable or reducing steroid dose before the baseline MRI scan (confirm with trial site)
• People currently receiving any other cancer treatment or taking any medicines that are not permitted alongside the study drug

Module 1 – Part A:

• People who have already received more than one prior treatment regimen containing a PARP inhibitor
• People with a blood clotting measurement (INR) above 1.5, unless they are taking a specific type of blood thinner (non-vitamin K antagonist oral anticoagulant)
• People with cancer that has spread to the membranes surrounding the brain and spinal cord (leptomeningeal disease), unless the spread is small in volume or has been previously treated and causes no or minimal symptoms
• People who require insulin to manage diabetes
• People currently taking a type of medication called ARA treatment (confirm with trial site)

Module 1 – Part B:

• People with an INR above 1.5 unless they are taking a specific permitted type of blood thinner
• People with leptomeningeal disease, unless the spread is small in volume or has been previously treated with radiotherapy and causes no symptoms

Module 2:

• People who have previously received a PARP inhibitor
• People with a known allergy to TMZ or dacarbazine, or to similar medicines
• People who have received more than one prior course of alkylating chemotherapy (including specific regimens — confirm with trial site)
• People who previously experienced severe blood count problems (grade 4 blood toxicity, serious infection-related low white cell counts, or significant bleeding due to low platelet counts) during prior alkylating chemotherapy
• People who have received the drug bevacizumab within the last 6 months
• People who require ongoing steroid treatment above a low daily dose for at least 4 weeks before starting the study

Module 3 – All panels:

• People with a positive Allen's test (a test checking blood flow in the hand — confirm with trial site)
• People with a BMI above 30 or body weight above 100kg
• People who experience claustrophobia (fear of enclosed spaces, which may affect MRI scans)
• People with metal implants in their body
• People with an INR above 1.5
• People taking medicines that reduce stomach acid

Module 3 – Panel 1:

• People who have had more than one prior PARP inhibitor-based treatment regimen
• People with leptomeningeal disease

Module 3 – Panel 2:

• People who have previously received a PARP inhibitor
• People