A phase 2 study of combination therapy with irinotecan/ S-1 (IRIS) plus panitumumab as second-line chemotherapy for metastatic colorectal cancer
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ABSTRACT:
DISEASE(S): Colonrectal Cancer
PROVIDER: 2620105 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Interventions: TS-1 administered for 14 days followed by 7 days rest according to body surface area. L-OHP is administered intravenously in 100 mg/m2 at day 1. Bevacizumab is administered intravenously in 7.5 mg/kg at day 1 Cycles are repeated every 3 weeks
Primary outcome(s): progression-free survival(PFS)
Study Design: Single arm Non-randomized
| 2624416 | ecrin-mdr-crc
Project description:<p>The SUCCESS-A Study (<a href="http://www.success-studie.de">http://www.success-studie.de</a>) is a randomized Phase III study of response to treatment of early primary breast cancer with adjuvant therapy after surgical resection. The primary outcome is disease-free survival and secondary outcomes are overall survival and toxicity. The study design includes comparison of two pairs of treatment regimes performed in sequence. The first randomization contrasts treatment with and without Gemcitabine (3 cycles of Epirubicin-Fluorouracil-Cyclophosphamide(FEC)-chemotherapy, followed by 3 cycles of Docetaxel(D)-chemotherapy versus 3 cycles of Epirubicin-Fluorouracil-Cyclophosphamide(FEC), followed by 3 cycles of Gemcitabine-Docetaxel(DG)-chemotherapy). The second randomization contrasts treatment with Zoledronate for two versus five years. Patients were recruited from 2005 to 2007 and a total of 3754 patients were included from 250 study sites across Germany. Genome-wide SNP microarray data and phenotype outcomes for the first phase of the study (treatment with and without Gemcitabine) are included in the GARNET (Genomics and Randomized Trials Network) pharmacogenomic study in this dbGaP submission. (The Zoledronate treatments are still underway).</p> <p>SUCCESS-A is a an open-label, multicenter, 2x2 factorial design, randomized controlled, Phase III study comparing the disease free survival after randomization in patients treated with 3 cycles of Epirubicin-Fluorouracil-Cyclophosphamide(FEC)-chemotherapy, followed by 3 cycles of Docetaxel(D)-chemotherapy versus 3 cycles of Epirubicin-Fluorouracil-Cyclophosphamide(FEC), followed by 3 cycles of Gemcitabine-Docetaxel(DG)-chemotherapy, and to compare the disease free survival after randomization in patients treated with 2 years of Zoledronate versus 5 years of Zoledronate in patients with early primary breast cancer. Patients were required to have histopathological proof of axillary lymph node metastases (pN1-3) or high risk node negative, defined as: pT>2 or histopathological grade 3, or age , ≤ 35 or negative hormone receptor, but were not allowed to have evidence of distant disease. Patients were entered into the study no later than 6 weeks after complete resection of the primary tumor. No antineoplastic treatment other than surgical treatment, the defined cytotoxic and endocrine treatment, and radiotherapy was allowed prior to study entry and during the course of the study. After surgery, leading to complete resection of the invasive and intraductal components of the primary tumor, patients were randomized to one of the following two treatments for the first phase of the project (which is included in this GARNET pharmacogenomics study):</p> <p><b>AA</b>: 3 cycles of 5-Fluorouracil 500 mg/m² i.v. body surface area and Epirubicin 100 mg/m² i.v. and Cyclophosphamide 500 mg/m² i.v., (FEC100), each administered on day 1, repeated on day 22, subsequently followed by 3 cycles of Docetaxel 75 mg/m² body surface area i.v. (D), and Gemcitabine 1000 mg/m² i.v. (30 min infusion) (G), administered on day 1, followed by Gemcitabine 1000 mg/m² i.v. (30 min infusion) on day 8, repeated on day22</p> <p><b>AB</b>: 3 cycles of 5-Fluorouracil 500 mg/m² i.v. body surface area and Epirubicin 100 mg/m² i.v. and Cyclophosphamide 500 mg/m² i.v., (FEC100), each administered on day 1, repeated on day 22, subsequently followed by 3 cycles of Docetaxel 100 mg/m² body surface area i.v. (D), administered on day 1, repeated on day 22</p> <p>A second randomization was made for assigning patients to one of the following two subsequent treatments for the second phase of the project (NOT included in the pharmacogenetic study in this dbGaP submission):</p> <p><b>BA</b>: Zoledronic acid 4 mg i.v., every 3 months for the duration of two years, subsequently followed by zoledronic acid 4 mg i.v., every 6 months for the duration of additional three years</p> <p><b>BB</b>: Zoledronic acid 4 mg i.v., every 3 months for the duration of two years</p> <p>Patients with positive hormone receptor status (≥10% positively stained cells for estrogen and/or progesterone) of the primary tumor were recommended to receive Tamoxifen treatment 20 mg p.o. per day for 2 years, after the end of chemotherapy . Subsequent to chemotherapy, postmenopausal patients with positive hormone receptor status were recommended to be treated with Anastrozole (Arimidex®) 1 mg p.o. for additional 3 years, premenopausal patients will continue Tamoxifen treatment for those additional 3 years. In addition to tamoxifen, all patients with positive hormone receptor status of the primary tumor and under the age of 40 or restart of menstrual bleeding within 6 months after the completion of cytostatic treatment or with premenopausal hormone levels as defined below were recommended to receive Goserelin (Zoladex®) 3.6 mg subcutaneously every 4 weeks over a period of 2 years following chemotherapy. Premenopausal endocrine status will be assumed, if the following serum levels are met: LH < 20 mIE/ml, FSH < 20 mIE/ml and E2 > 20 pg/ml. Endocrine therapy will start after the end of chemotherapy.</p> <p>All patients with breast conserving therapy or more than 3 axillary lymph node metastases or in the following cases after mastectomy will receive adjuvant radiotherapy: T3/T4-carcinoma, T2-carcinoma > 3 cm, multicentric tumor growth, lymphangiosis carcinomatosa or vessel involvement, involvement of the pectoralis fascia or a safety margin < 5 mm. Radiotherapy was usually performed after the chemotherapy and parallel to the beginning of the zoledronic acid therapy.</p> <p>Initially, DNA was extracted for performing SNP microarray assays using blood collected at baseline prior to the first randomization. However, the first set of SNP microarray results indicated a quality problem with approximately 50% of the DNA samples. A majority of the problematic samples were replaced with DNA extracted from redrawn blood. The remaining problematic samples were 'restored' using an Illumina FFPE Restoration procedure. A total of 3322 subjects (1638 from arm AA and 1684 from arm AB) were successfully genotyped. Among those, 1771 were from original blood samples, 1092 from redrawn blood samples and 459 from restored blood samples.</p> <p>The SUCCESS-A study is part of the Genomics and Randomized Trials Network (GARNET, <a href="http://www.garnetstudy.org">http://www.garnetstudy.org</a>) funded by the National Human Genome Research Institute (NHGRI). The overarching goal is to identify novel genetic factors that contribute to disease-free survival for breast cancer patients using different forms of chemotherapy through large-scale genome-wide association studies of treatment response in randomized clinical trials. The study was conducted at the University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Germany. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were performed at the GARNET Coordinating Center at the University of Washington.</p>
| phs000547 | dbGaP
Project description:Interventions: Treatment by IRIS+Rmab Ramucirumab at a dose of 10mg/kg was administered as a 120-min infusion and irinotecan at a dose of 150mg/m2 by adjustment by UGT1A1 was administered as a 90-min infusion every 3 weeks. The dose of S-1 was determined according to the patient’s body surface area (BSA). Specifically, the drug was administered orally twice daily for 14 consecutive days at a dose that did not exceed 40 mg/m2 based on BSA as follows-BSA<1.25m2, 40 mg; BSA 1.25-1.5 m2, 50mg twice daily; and BSA >1.5 m2, 60 mg by adjustment of Ccr. Premedication with a 5-HT3 antagonist combined with dexamethasone (+/-) an NK-1 antagonist was recommended in patients before the administration of irinotecan. This treatment was administered until disease progression, unacceptable toxicity, withdrawal of consent, or the physician’s decision to terminate treatment.
Primary outcome(s): progrssion free survival (PFS)
Study Design: Single arm Non-randomized
| 2643378 | ecrin-mdr-crc
Project description:Interventions: FOLFIRI + bevacizumab consisted of bevacizumab 5mg/kg as a 90-minute infusion, then, l-LV 200 mg/m2 as a 2-hour infusion, and irinotecan 150 mg/m2 given as a 90-minute infusion, followed by bolus FU 400 mg/m2 and a 46-hour infusion FU 2,400 mg/m2, repeated every 2 weeks.
IRIS + bevacizumab consisted of bevacizumab 7.5mg/kg as a 90-minute infusion, then, irinotecan 150 mg/m2 given as a 90-minute infusion, followed by oral S-1 (40 mg/m2) twice daily 14 days (day 3 to 16) followed by 5 days rest, repeated every 3 weeks.
Primary outcome(s): safety
Study Design: Parallel Randomized
| 2616274 | ecrin-mdr-crc
Project description:Interventions: Combination therapy of panitumumab plus irinotecan: Patients receive panitumumab (intravenous dose of 6 mg/kg) plus intraveous infusion of irinotecan of 150 mg/m2 (body surface area). Treatment cycles are repeated every 2 weeks until disease progression, unacceptable adverse events, or withdrawal of consent.
Primary outcome(s): Response Rate
Study Design: single arm study, open(masking not used), no treatment control/standard of care control, single assignment, treatment purpose
| 2614550 | ecrin-mdr-crc
Project description:We performed RNA sequencing on tumors harvested from OV5398 (ovarian) PDX treated for 40-50 days with either control vehicle (PEG), 100 mg/kg BID INX-315 or 200 mg/kg QD INX315.
2023-11-22 | GSE243151 | GEO
Project description:We performed RNA sequencing on tumours harvested from GA0103 (gastric cancer) PDX treated for 40-50 days with either control vehicle or 100 mg/kg BID INX-315.
2023-11-22 | GSE243153 | GEO
Project description:Intervention name : trifluridine/tipiracil
INN of the intervention : trifluridine/tipiracil
Dosage And administration of the intervention : Trifluridine/tipiracil was given in a dose of 35-75 mg twice daily (after breakfast and dinner) (70-150 mg/day) from after dinner on Day 1 to after breakfast on Day 6 and from after dinner on Day 8 to after breakfast on Day 13. Treatment was given orally for 5 consecutive days followed by a 2-day rest. This treatment was repeated twice, followed by a 14-day rest. This 28-day cycle was repeated until the criteria for withdrawal of the study treatment were met.
Intervention name : bevacizumab
INN of the intervention : bevacizumab
Dosage And administration of the intervention : Bevacizumab 5 mg/kg was given as a 30-min continuous intravenous infusion on Day 1 and Day 15.
Control intervention name : fluorouracil
INN of the control intervention : fluorouracil
Dosage And administration of the control intervention : [Treatment with FOLFIRI + bevacizumab] Fluorouracil 400 mg/m2 was given by rapid intravenous injection on Day 1, followed by a 46-h continuous intravenous infusion of 2400 mg/m2. Each cycle was 14 days, and treatment was repeated until the criteria for withdrawal of the study treatment were met.
Control intervention name : TS-1(tegafur + gimeracil + oteracil potassium)
INN of the control intervention : TS-1(tegafur + gimeracil + oteracil potassium)
Dosage And administration of the control intervention : [Treatment with TS-1+ irinotecan +bevacizumab (3-week cycles) ] TS-1 is given orally in a dose of 40-60 mg twice daily (after breakfast and dinner) in accordance with body-surface area (80-120 mg/day), starting from after dinner on Day 1 to after breakfast on Day 15, followed by a 7-day rest. Each cycle was 21 days, and treatmen
Primary outcome(s): efficacy
Overall survival
Study Design: Randomized, open-label, comparative study
| 2611617 | ecrin-mdr-crc
Project description:<p>The GOLDN study was initiated to assess how genetic factors interact with environmental (diet and drug) interventions to influence blood levels of triglycerides and other atherogenic lipid species and inflammation markers (registered at clinicaltrials.gov, number <a href="https://clinicaltrials.gov/ct2/show/NCT00083369" target="_blank">NCT00083369</a>). The study recruited Caucasian participants primarily from three-generational pedigrees from two NHLBI Family Heart Study (FHS) field centers (Minneapolis, MN and Salt Lake City, UT). Only families with at least two siblings were recruited and only participants who did not take lipid-lowering agents (pharmaceuticals or nutraceuticals) for at least 4 weeks prior to the initial visit were included. The diet intervention followed the protocol of Patsch et al. (<a href="https://www.ncbi.nlm.nih.gov/pubmed/1420093" target="_blank">1992</a>). The whipping cream (83% fat) meal had 700 Calories/m2 body surface area (2.93 mJ/m2 body surface area): 3% of calories were derived from protein (instant nonfat dry milk) and 14% from carbohydrate (sugar). The ratio of polyunsaturated to saturated fat was 0.06 and the cholesterol content of the average meal was 240 mg. The mixture was blended with ice and flavorings. Blood samples were drawn immediately before (fasting) and at 3.5 and 6 hours after consuming the high-fat meal. The diet intervention was administered at baseline as well as after a 3-week treatment with 160 mg micronized fenofibrate. Participants were given the option to complete one or both (diet and drug) interventions. Of all participants, 1079 had phenotypic data and provided appropriate consent, and underwent whole genome sequencing through the Trans-Omics for Precision Medicine (TOPMed) program.</p> <p>Comprehensive phenotypic and pedigree data for GOLDN study participants are available through dbGaP <a href="./study.cgi?study_id=phs000741">phs000741</a>.</p>
| phs001359 | dbGaP
Project description:The aim of this study was to examine the hippocampus, frontal cortex and dorsal raphe of Dark Agouti rats with gene expression arrays (Illumina RatRef bead arrays) looking for possible mechanisms and new candidates contributing to the effects of a single dose of MDMA (15 mg/kg) 3 weeks earlier or venlafaxine (40 mg/kg) administration for 3 weeks continously. We also examined the possible interaction between the single dose MDMA treatment and the continous venlafaxine treatment described above.
2013-06-01 | GSE47541 | GEO