Capri trial pancreatic cancer
Accepts Healthy Volunteers: No Criteria. For Cohort D, Part I, patients may have any non-mucinous epithelial ovarian cancer including histologies such as clear cell, or endometrioid.
Pathology must be reviewed internally at the University of Pennsylvania, Johns Hopkins University, or Harvard University prior to initiation of treatment. All patients under consideration for Cohorts A, B, C, and D, must be willing to undergo mandatory tumor biopsies non-target lesion. Patients should have at least one lesion non-target for biopsy. Patients who undergo attempted biopsies that are unsuccessful may still enroll and receive study drug.
Patients with known BRCA germline mutations will be permitted to enroll up to a maximum of 10 subjects per cohort.
Other HRD mutations will be reviewed for consideration for enrollment by study review committee or University of Pennsylvania principal investigator. Patients must be at least 2 weeks from previous therapy for their ovarian cancer chemotherapy, hormonal therapy, and radiation therapy, or investigational agents; 6 weeks for mitomycin C to initiate screening and 3 weeks from previous therapy to initiate treatment.
Hormones for breast cancer management may be continued at the discretion of the provider. For Cohort A, there is no limit to number of prior regimens.
For Cohort B, patients may not have had more than 3 prior cytotoxic therapies since the development of platinum-resistance. Patients for Cohort D, Part I dose escalation , patients may be either platinum-sensitive with no limit on prior regimens.
Platinum-resistant patients are eligible but they may not have received more than 3 prior cytotoxic therapies since development of platinum resistance. These patients must demonstrate adequate bone marrow function as determined by the treating physician. If the prior PARP inhibitor used was olaparib, then patients must have received treatment without significant toxicity or the need for a permanent dose reduction.
Patients must be able to swallow oral medications capsules and tablets without chewing, breaking, crushing, opening, or otherwise altering the product formulation. They should not have gastrointestinal illnesses that would preclude the absorption of AZD or olaparib, which are oral agents. Able to understand and voluntarily sign a written informed consent, and are willing and able to adhere to the protocol requirements. Patients with a history of brain metastases diagnosed greater than one year prior to study entry may be considered if they received sterilizing therapy to the CNS resection or radiation and have been CNS recurrence-free for the one-year period.
Exclusion criteria: Patients with known brain metastases diagnosed within one year will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
Stable persistent Grade 2 peripheral neuropathy may be allowed as determined on a case-by-case basis at the discretion of the PI. Patients with platinum-related hypomagnesemia on replacement will be eligible. Patients with localized breast cancer who are disease free at least three years out from treatment may be eligible. Concomitant use of known strong CYP3A inhibitors e.
The required washout period prior to starting olaparib is two weeks. Concomitant use of known strong e. The required washout period prior to starting olaparib is five weeks for enzalutamide or phenobarbital and three weeks for other agents.
Major surgery within four weeks of starting study. Patients with a known hypersensitivity to AZD or olaparib or any of the excipients of the product.
Patients receiving any systemic chemotherapy or radiotherapy except for palliative reasons within three weeks prior to study treatment. Patients with known active hepatitis i. Hepatitis B or C due to risk of transmitting the infection through blood and other body fluids. Previous allogeneic bone marrow transplant or double umbilical cord blood transplantation dUCBT. Whole blood transfusions in the last days prior to entry to the study. Contacts and Locations. Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
References 1. CA Cancer J Clin ; 68 Therapeutic developments in pancreatic cancer: current and future perspectives. Nat Rev Gastroenterol Hepatol ; 15 Hackert T. Surgery for Pancreatic Cancer after neoadjuvant treatment. Ann Gastroenterol Surg ; 2 Ann Surg ; N Engl J Med ; Neoadjuvant and adjuvant chemotherapy in pancreatic cancer. Langenbecks Arch Surg ; Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection.
Arch Surg ; Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Gastrointestinal Tumor Study Group. Cancer ; 59 Adjuvant combination chemotherapy AMF following radical resection of carcinoma of the pancreas and papilla of Vater--results of a controlled, prospective, randomised multicentre study.
Eur J Cancer ; 29A Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer ; 95 Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group.
Long-term survival and metastatic pattern of pancreatic and periampullary cancer after adjuvant chemoradiation or observation: long-term results of EORTC trial Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet ; A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial.
JAMA ; Br J Cancer ; Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial.
Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the U.
Ann Surg Oncol ; 18 Open-label, multicenter, randomized phase III trial of adjuvant chemoradiation plus interferon Alfa-2b versus fluorouracil and folinic acid for patients with resected pancreatic adenocarcinoma. J Clin Oncol ; 30 Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial JASPAC J Clin Oncol ; 35 Ann Oncol ;mdu Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer ESPAC-4 : a multicentre, open-label, randomised, phase 3 trial.
Twombly R. Adjuvant chemoradiation for pancreatic cancer: few good data, much debate. J Natl Cancer Inst ; Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study.
J Clin Oncol ; 32 Adjuvant 5-fluorouracil and folinic acid vs observation for pancreatic cancer: composite data from the ESPAC-1 and -3 v1 trials. J Oncol Pract ; 13 Released on March 12, Accessed on March 21, Cancer Discov ; 8 JAMA Oncol ; 4 Support Center Support Center.
External link. Please review our privacy policy. It is hypothesised that removal of cisplatin and radiotherapy will have no significant effect or only a minor impact on the clinical response but result in substantially lower toxicity. Most patients typically relapse within 9—15 months form initial presentation and have median life expectancies of only 12—15 months without adjuvant therapy.
Data from two randomized clinical phase III trials showed that adjuvant chemotherapy results in significant increase of overall survival OS and disease-free survival DFS [ 2 , 3 ].
Therefore, adjuvant therapy with either 5-FU or gemcitabine is recommended according to the German S3 guidelines for exocrine pancreas carcinoma [ 4 ]. The last patient was enrolled end of First clinical results are expected for These excellent results could be ascribed to the several synergistic effects between the combined substances.
Radio-sensitising properties of 5-FU and cisplatin are well known. Although the final safety analysis is not yet performed we could give account on less GI-toxicity in the CapRI-trial. Nevertheless, the regimen is challenging and reduction of side effects is a useful goal. Heidelberg is responsible for overall trial management, regulatory affairs, statistical planning and analysis, trial registration and reporting as well as quality assurance.
The responsibility for external monitoring and pharmacovigilance is carried forward to independent Contract Research Organisations CRO. Further study centres will be recruited. The trial is sponsored by a private person, Dr.
Wild from Germany. The financial sponsor is not involved in the database management and has no access to the randomisation code. Patients will be recruited by the centres who will commit their participation. Due to the multimodal nature of the trial, all investigators will either be experienced oncologists, gastroenterologists, radio-oncologists or surgeons.
The board will monitor the trial data, in particular the safety data, and makes recommendations based on the periodically reviewed data. All chemotherapeutic and immunotherapeutic agents will be prepared and provided by the corresponding pharmacy.
Medication will be prepared for each patient specifically and delivered just prior to administration to the outpatient's department. Monitoring on site will be performed according to good clinical practice GCP guidelines.
Monitoring will be done by personal visits from clinical monitors according to the SOPs of the independent, external CRO.
Data management will be performed by the same CRO. Pharmacovigilance is outsourced to a further CRO specialized on safety issues. Both data bases will be aligned at the end of the trial.
The trial will also be performed in keeping with local legal and regulatory requirements. The medical secrecy and the Federal Data Protection Art will be followed.
Written informed consent will be obtained from each patient in oral and written form before inclusion in the trial and the nature, scope and possible consequences of the trial have been explained by a physician in detail.
The investigator will not undertake any measures specifically required only for the clinical trial until valid consent has been obtained. CapRI-2 focuses on hospitalised patients over 18 years of age with resected pancreatic adenocarcinoma during a 24 months period and started in October Men and women over 18 years of age with histological proven R0 or R1 resected [ 18 ] pancreatic adenocarcinoma will be screened for participation in the clinical trial.
Patients will be contacted first-time by the sub- investigators either during their postoperative hospital stay or after discharge at the outpatient's department. CapRI-2 is an open, controlled, prospective, randomized, multicentre phase II trial with three parallel study arms. The first de-escalation step is in study arm B where cisplatin is omitted CapRI-light.
The second de-escalation will be tested in study arm C where beside cisplatin also radiotherapy is cancelled CapRI-ultra-light.
No interim analysis is planed for this trial. Primary objective is the comparison of the treatment groups with respect to six-month event-free survival.
Secondary objectives are comparison of the treatment groups with respect to safety, OS, Recurrence-Free Survival RFS , Quality of Life QoL , screening for predictive markers, and accompanying translational research focussing mainly on immunological parameters. All patients enrolled will be identifiable throughout the study. The investigator will maintain a personal list of patient numbers and patient names to enable records to be found at a later date. Upon inclusion each patient receives a unique identification number.
By the randomisation number, it is possible to identify the order in which the patients entered the randomized study period at the centre in question. Randomisation will be stratified by centre; it will be done and documented centrally and send by fax. The randomisation list will be kept in safe and confidential custody at the involved CRO.
The method of randomisation whether fixed block size or randomly determined block size and the block sizes themselves will not be disclosed to the study centres, the monitors or any other person involved in the study conduct. This information will be kept with the randomisation list. The porta hepatis, origins of the celiac axis and superior mesenteric artery will be included.
The fields must include the entire duodenal C-loop as seen on pre-operative CT scan. Total dose will be Simulation should be done with the patient in the supine position with "arms up" position.
A treatment planning CT is required to allow 3-D conformal treatment planning. Conventional 3-D treatment techniques as well as intensity modulated radiotherapy IMRT could be used for radiotherapy. Furthermore a multi-leaf collimator is required to allow customized blocking and IMRT. Equipment: greater than or equal to 6 MeV photons should be used. Two to three hours before and after Cisplatin dose the patients will receive hydration of at least 2 litres.
Patients will be taught to drink at least 1 litre during the day. Blood will be drawn for intensive immunological studies. All patients must have appropriate lab and radiographic studies conducted prior to study enrolment to meet eligibility criteria. Lab parameters will be obtained at least weekly and imaging will be performed every three months.
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