Evolve: A post PARP inhibitor clinical translational phase II trial of cediranib-olaparib in ovarian cancer—A Princess Margaret Consortium – GCIG Phase II Trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5521-5521 ◽  
Author(s):  
Stephanie Lheureux ◽  
Ana Oaknin ◽  
Swati Garg ◽  
Jeffrey Bruce ◽  
Neesha C. Dhani ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Tumor Biopsy ◽  
Ps Ii

5521 Background: PARP inhibitors (PARPi) are approved therapies in high grade serous ovarian cancer (HGSOC). There are few studies after PARPi progression and correlation with dynamic changes in resistance. We hypothesized that PARPi resistance could be overcome by adding an anti-angiogenic. Methods: We report the first phase 2 trial assessing the combination of olaparib and cediranib after PARPi failure in HGSOC. This investigator initiated study included three cohorts of 10 evaluable patients (pts): i) platinum sensitive post PARPi (PS), ii) platinum resistant post PARPi (PR) and iii) exploratory cohort of pts re-challenged with chemotherapy post PARPi progression (PE) (NCT02681237). The primary objective was to determine objective response rate by RECIST v1.1 and progression free survival (PFS) at 16 weeks. Secondary objectives were to evaluate safety, PFS, overall survival (OS) and mechanisms of PARPi resistance. Pts who had radiographic progression on any PARPi were eligible. Archival tumor at initial diagnosis and baseline tumor biopsy at PARPi progression were mandatory. Pts received olaparib tablets 150mg BID with cediranib 20mg QD until progression or unacceptable toxicity. CT scans were performed every 8 weeks. Whole exome and RNA sequencing were performed on paired tumors tissues. Results: Thirty-four pts were enrolled. BRCA1/2 mutations were found in 9/11 PS, 8/10 PR and 7/13 PE pts. By RECIST1.1, four partial responses were observed (2 in PR and 2 in PE cohorts) and 18 stable disease. The 16−week PFS was 54.5% (31.8−93.6) in PS, 50% (26.9−92.9) in PR and 36% (15.6−82.8) in PE, respectively. OS at 1 year was 81.8% (61.9−100) in PS, 64.8% (39.3−100) in PR and 39.1% (14.7−100) in PE. Main related adverse events were anemia, hypertension, diarrhea and fatigue, grade 3 < 10%. Molecular analyses identified different mechanisms of PARPi resistance in ~77% of evaluable pts with matched pre-post PARPi progression biopsies such as reversion mutations in BRCA1/2 and other homologous repair (HR) genes; BRCA, HR and MDR upregulation, CCNE amplification and RIG-I like receptor downregulation. Conclusions: Treatment with olaparib-cediranib after PARPi failure was feasible and met the predefined bar for efficacy in each cohort. This is the largest clinical trial prospectively evaluating PARPi failure and correlating tissue genomic mechanisms of resistance. Clinical trial information: NCT02681237.

Phase II clinical trial of six mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS5615-TPS5615
Author(s):  
Shibani Nicum ◽  
Claire E Brooks ◽  
Rose Wharton ◽  
Lucy Boyle ◽  
Stanley B. Kaye ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Brca Mutation ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Xenograft Model ◽  
Phase Iii ◽  
Tpmt Activity ◽  
Compromise Design

TPS5615 Background: BRCA1 and BRCA2 genes are critical in homologous recombination DNA repair and have been implicated in familial breast and ovarian cancer tumorigenesis. Tumor cells with these mutations demonstrate increased sensitivity to cisplatin and poly(ADP-ribose) polymerase (PARP) inhibitors. 6MP was identified in a screen for novel drugs and found to selectively kill BRCA-defective cells in a xenograft model as effectively as the PARP inhibitor, AGO14699, even after these cells had acquired resistance to a PARP inhibitor or cisplatin (Issaeva 2010). Exploiting the genetic basis of these tumours enables us to develop a more tailored approach to therapy for patients with BRCA mutated cancers. This multi-center phase II single arm trial was set up to investigate the activity and safety of 6MP with methotrexate in patients with breast or ovarian cancer who are known to have a BRCA mutation. Methods: Two-stage Simon compromise design (Jung 2001, Jung 2004) with α=0.20, power=90% to detect an increase in activity from 10 to 20%. 1st stage: if ≤ 3/30 evaluable patients respond at 8 weeks the trial will be stopped for futility; 2nd stage: if ≥9/65 evaluable patients respond at 8 weeks the treatment will be regarded as potentially effective and a phase III trial will be considered if the treatment appears safe and well-tolerated. 65 patients with BRCA defective cancer progressing after at least one prior chemotherapy or relapsed platinum resistant ovarian cancer, ECOG performance status 0-2 will be recruited and treated with daily 6MP (75mg/m2 ) and weekly methotrexate (20mg/m2) until progression. The starting dose was later reduced by 25% due to excess of expected toxicity. Patients with low TPMT activity or a low/low genotype are excluded due to the risk of increased toxicity. Prior treatment with a PARP inhibitor is permissible. Primary outcome: objective response at 8 weeks: complete, partial response or stable disease defined by RECIST 1.1. Secondary outcomes include safety, PFS, OS and quality of life. Of the 46 patients screened for TMPT activity between 15 Jun2009 and 05Dec 2012 from 12 UK sites, 31 patients were recruited. The pre-specified activity goal for the 1st stage was met and accrual into the 2nd stage continues. Clinical trial information: 2009-016846-16.

scholarly journals Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours

2019 ◽  
Vol 122 (4) ◽  
pp. 483-490 ◽  
Author(s):  
Corran Roberts ◽  
Victoria Y. Strauss ◽  
Sylwia Kopijasz ◽  
Charlie Gourley ◽  
Marcia Hall ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Phase Ii ◽  
Clinical Benefit ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Acquired Resistance ◽  
Xenograft Model ◽  
Progression Free Survival ◽  
Breast Cancer Patients

Abstract Background Tumour cells with BRCA1/2 gene mutations demonstrate increased sensitivity to platinum and poly (ADP-ribose) polymerase (PARP) inhibitors. 6-mercaptopurine (6MP) was found to selectively kill BRCA-defective cells in a xenograft model as effectively as the PARP inhibitor AG014699, even after these cells acquired resistance to a PARP inhibitor or cisplatin. Methods This phase II single-arm trial investigated the activity of 6MP 55–75 mg/m2 per day, and methotrexate 15–20 mg/m2 per week in advanced breast or platinum-resistant ovarian cancer patients with a BRCA1/2 germline mutation, who had progressed after ≥1 previous line of chemotherapy. The primary outcome was objective response including stable disease (SD) as an assessment of clinical benefit rate (CBR), at 8 weeks, by RECIST v1.1. Secondary outcomes included overall survival (OS) and progression-free survival (PFS). Results In total, 67 evaluable patients were recruited; 55 ovarian and 11 breast cancer patients. In total, 21 patients had SD (31%), one had a partial response (1.5%); CBR was 33% at 8 weeks. In total, 12/67 patients (18%) had SD at 16 weeks. In total, five ovarian cancer patients had SD for over 200 days. Median OS was 10.3 months (95% CI 6.9–14.5), median PFS 1.9 months (1.7–2.8). Conclusions The overall activity of 6MP and methotrexate in these patients was low; however, there was a small group of patients who appeared to derive longer-term clinical benefit. Trial registration NCT01432145 http://www.ClinicalTrials.gov.

Randomized phase II study of vandetanib (VAN) alone or in combination with carboplatin and paclitaxel (CP) as first-line treatment for advanced non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7544-7544 ◽  
Author(s):  
J. Heymach ◽  
L. Paz-Ares ◽  
F. De Braud ◽  
M. Sebastian ◽  
D. J. Stewart ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Circulating Endothelial Cells ◽  
Once Daily ◽  
Randomized Phase Ii ◽  
Biomarker Analysis

7544 Background: VAN (ZD6474) is a once-daily oral agent that selectively inhibits VEGFR, EGFR and RET signaling. This randomized phase II trial investigated VAN alone or in combination with CP vs CP. Methods: Eligible patients (pts) had previously untreated locally advanced or metastatic (IIIB-IV) NSCLC. The primary objective was to determine whether VAN (300 mg/day) ± CP (C, target AUCss = 6 mg/ml·min; P; 200 mg/m2 iv) prolonged progression-free survival (PFS) vs CP (75% power to detect 30% prolongation; 1-sided P=0.2). An initial run-in phase had established VAN 300 mg/day as an appropriate dose to be given with CP. Results: A total of 181 pts (median age 61 yrs, range 27–83) received VAN (n=73), VAN + CP (n=56) or CP (n=52). The primary objective was met, with VAN + CP prolonging PFS vs CP (HR = 0.76, 95% CI 0.50–1.15; P=0.098): median PFS = 24 wks (VAN + CP) and 23 wks (CP). The VAN monotherapy arm was stopped early after a planned interim PFS analysis met the criterion for discontinuation (HR > 1.33 vs CP). The objective response rates were 32%, 25% and 7% for VAN + CP, CP and VAN, respectively. Overall survival (OS), a secondary endpoint, was not significantly different between pts receiving VAN + CP or CP (HR = 1.07, 95% CI 0.63–1.81; P=0.595). Exploratory subgroup analyses suggest advantages in PFS and OS for VAN + CP vs CP for the 56 female pts. There was a higher incidence of some adverse events with VAN + CP vs CP, including rash (64% vs 33%), diarrhea (53% vs 32%), asymptomatic QTc-related events (22% vs 4%) and hypertension (32% vs 4%). Pts receiving VAN + CP, including 7 who entered with CNS metastases and 11 with squamous histology, did not experience any intracranial bleeding, or hemoptysis of CTC grade 2 or higher. A biomarker analysis, including circulating endothelial cells and 35 plasma angiogenic factors and cytokines, suggests several potential markers predictive of clinical outcome and will be reported separately. Conclusions: In this randomized phase II trial of 1st-line advanced NSCLC, VAN + CP met the primary endpoint of prolonging PFS vs CP alone but did not provide a detectable survival advantage. No significant financial relationships to disclose.

PRECEDENT: A Randomized Phase II Trial Comparing Vintafolide (EC145) and Pegylated Liposomal Doxorubicin (PLD) in Combination Versus PLD Alone in Patients With Platinum-Resistant Ovarian Cancer

2013 ◽  
Vol 31 (35) ◽  
pp. 4400-4406 ◽  
Author(s):  
R. Wendel Naumann ◽  
Robert L. Coleman ◽  
Robert A. Burger ◽  
Edward A. Sausville ◽  
Elzbieta Kutarska ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Phase Ii Trial ◽  
Folate Receptor ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Platinum Resistant ◽  
Randomized Phase Ii

Purpose Vintafolide (EC145) is a folic acid–desacetylvinblastine conjugate that binds to the folate receptor (FR), which is expressed on the majority of epithelial ovarian cancers. This randomized phase II trial evaluated vintafolide combined with pegylated liposomal doxorubicin (PLD) compared with PLD alone. The utility of an FR-targeted imaging agent, 99mTc-etarfolatide (EC20), in selecting patients likely to benefit from vintafolide was also examined. Patients and Methods Women with recurrent platinum-resistant ovarian cancer who had undergone ≤ two prior cytotoxic regimens were randomly assigned at a 2:1 ratio to PLD (50 mg/m2 intravenously [IV] once every 28 days) with or without vintafolide (2.5 mg IV three times per week during weeks 1 and 3). Etarfolatide scanning was optional. The primary objective was to compare progression-free survival (PFS) between the groups. Results The intent-to-treat population comprised 149 patients. Median PFS was 5.0 and 2.7 months for the vintafolide plus PLD and PLD-alone arms, respectively (hazard ratio [HR], 0.63; 95% CI, 0.41 to 0.96; P = .031). The greatest benefit was observed in patients with 100% of lesions positive for FR, with median PFS of 5.5 compared with 1.5 months for PLD alone (HR, 0.38; 95% CI, 0.17 to 0.85; P = .013). The group of patients with FR-positive disease (10% to 90%) experienced some PFS improvement (HR, 0.873), whereas patients with disease that did not express FR experienced no PFS benefit (HR, 1.806). Conclusion Vintafolide plus PLD is the first combination to demonstrate an improvement over standard therapy in a randomized trial of patients with platinum-resistant ovarian cancer. Etarfolatide can identify patients likely to benefit from vintafolide.

Final report of a phase I/II study of veliparib (Vel) in combination with 5-FU and oxaliplatin (FOLFOX) in patients (pts) with metastatic pancreatic cancer (mPDAC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4015-4015 ◽  
Author(s):  
Michael J. Pishvaian ◽  
Hongkun Wang ◽  
Sarah Parenti ◽  
Aiwu Ruth He ◽  
Jimmy J. Hwang ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Final Report ◽  
Cancer Syndrome ◽  
Previously Treated ◽  
Ecog Ps

4015 Background: 17 – 25% of mPDACs harbor DNA damage response (DDR) mutations, the presence of which can be predictive of a response to platinum and PARP inhibitor-based therapy. The PARP inhibitor, Vel is a potent sensitizing agent for, and has been safely combined with DNA-damaging chemotherapies. Methods: We initiated a Phase I/II trial of Vel + FOLFOX in pts with mPDAC. Pts received standard mFOLFOX6 except without the 5FU bolus, Q2 weeks. For the Phase I portion, a 3+3 dose escalation of Vel identified a recommended Phase II dose of 200mg orally BID, days 1-7, Q2 weeks. For the Phase II portion, we enrolled two cohorts: 1) Untreated pts; 2) Previously treated pts. Also, for Phase II, pts were pre-selected if they had either a pathogenic germline or somatic DDR mutation (e.g. BRCA1/2, PALB2, ATM), and/or a family history suggestive of a breast or ovarian cancer syndrome (labelled FH+). Objective response rate (ORR) was the primary objective of the Phase II cohorts; key secondary endpoints were median progression-free survival (PFS) and overall survival (OS). Results: Between 01-2011 and 12-2018, 64 pts received treatment, 31 in Phase I, and 15 untreated and 18 previously treated in Phase II. The combination was well tolerated, with the main Grade 3/4 AEs being myelosuppression (16%) and nausea/vomiting (6%). Of the 64 pts, 55% were male; median age was 64; 95% had an ECOG PS of 1; 78% were platinum-naïve; 69% were FH+; and 27% had a known DDR mutation. 57 pts were evaluable for response, and the ORR, PFS, and OS for the different pt subgroups are detailed below. The Phase II cohorts achieved the primary endpoint of an ORR ≥ 25%. Most notably, plat-naïve, FH+, and DDR mutation+ pts had an ORR of 58%. Conclusions: The combination of Vel + FOLFOX is safe, well tolerated, and shows promising efficacy particularly in plat-naïve pts who are FH+ and/or harbor DDR mutations. A randomized trial to assess the contribution of Vel to the regimen is warranted. Clinical trial information: NCT01489865. [Table: see text]

A randomized phase II trial of weekly docetaxel plus either cisplatin or oxaliplatin in patients with previously untreated advanced gastric cancer: Preliminary results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4566-4566
Author(s):  
S. Sym ◽  
S. Park ◽  
J. Park ◽  
K. Kwon ◽  
I. Jung ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tolerability Profile ◽  
Preliminary Results ◽  
Weekly Docetaxel ◽  
Randomized Phase Ii ◽  
Significant Difference

4566 Background: Docetaxel, in combination with cisplatin or oxaliplatin, has demonstrated efficacy against AGC. This randomized phase II trial evaluated two weekly docetaxel-based regimens to see which would be most promising according to objective response rate (ORR) as first-line therapy in AGC. Methods: Chemotherapy-naïve patients with measurable unresectable and/or metastatic gastric adenocarcinoma and a performance status ≤2 were randomly assigned to receive docetaxel (35 mg/m2) weekly on days 1 and 8 of a 21-day cycle plus either cisplatin (60 mg/m2 on day 1) (arm A) or oxaliplatin (120 mg/m2 on day 1) (arm B). Toxicity was assessed on days 1, 8, and 21 of each cycle, and response was evaluated every 2 cycles. Results: Between March 2007 and December 2008, 61 eligible patients entered. In Arm A, 29 patients were evaluable for objective response and 31 for safety. In Arm B, 28 patients were evaluable for objective response and 30 for safety. Median age was 52 years and disease status was comparable for both arms. Ten of 29 (34.5%) patients had a confirmed objective response in the arm A (95% confidence interval [CI] 17.1–51.8%) and 11 of 28 (39.2%) patients had a confirmed objective response in the arm B (95% CI 21.1- 57.2%). No significant difference was noted between the arms both for ORR (p=0.202) or for disease control (58.6% and 82.1%, respectively, p=0.082). Median progression free survival time was 4.4 month in the arm A and 4.3 months in the arm B (Hazard ratio = 0.936; 95% CI, 0.503–1.744; p = 0.836). There was no relevant difference in the occurrence of overall grade ¾ toxicity between the two arms (51.6% vs. 46.6%, respectively; p=0.800). Neutropenia was the most common grade 3/4 toxicity (32.3% vs. 36.6%, respectively). There was one treatment related death in Arm B. Conclusions: The preliminary results showed that both treatment arms have similar clinical efficacy as front-line treatment in AGC. Each regimen has a manageable tolerability profile. The accrual is ongoing. No significant financial relationships to disclose.

Phase II trial of anti-transforming growth factor-beta (TGFß) monoclonal antibody GC1008 in relapsed malignant pleural mesothelioma (MPM).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7077-7077 ◽  
Author(s):  
James Stevenson ◽  
Hedy Lee Kindler ◽  
Daniel Schwed ◽  
Anjana Ranganathan ◽  
Mona Jacobs-Small ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Phase Ii Trial ◽  
Treatment Plan ◽  
Single Agent ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Modified Recist

7077 Background: TGFβ is a pleiotropic cytokine overexpressed by MPM. Based on preclinical data documenting a key role for TGFβ in promoting growth and progression of MPM, we are conducting a phase II trial of GC1008 in patients (pts) with progressive MPM. Methods: Pts with progressive MPM by modified RECIST criteria and PS 0-1 with 1-2 prior systemic therapies (at least 1 pemetrexed-based) are eligible. Treatment plan: GC1008 3mg/kg IV over 90 minutes every 21 days. Responses are assessed by modified RECIST every 6 weeks. The primary endpoint is progression-free survival (PFS) rate at 3 months; secondary objectives include safety with GC1008, response rate by modified RECIST, time to progression (TTP), and overall survival (OS). Results: The modified Gehan stage 1 stopping criterion of 1/13 pts with 3 month PFS has been exceeded. To date, 13 pts (10 PS 0; 3 PS 1) with MPM (median age 69; 2F, 11M; 11 epithelial, 1 sarcomatoid, 1 biphasic) enrolled. Treatment-related toxicities include G1/2 fatigue (3 pts), nausea (1 pt) and xerosis (1 pt). Other adverse events possibly related to GC1008 were rapid disease progression in 1 pt after 2 cycles, and G2 skin keratoacanthoma in 1 pt after 5 cycles. Three pts met the primary objective of 3 month PFS at 4.1, 4.2 and 9 months each. Stable disease (SD) was seen in 3 pts (23%). Median TTP is 1.4 months (95% CI 1.2-∞); median OS is 13 months (95% CI 6-∞). Increased serum mesothelin levels have closely tracked disease progression. Serum from 6/13 pts showed new antibodies against MPM tumor lysates as measured by immunoblotting. Two of 3 pts with SD had anti-tumor antibody responses. Mean baseline plasma level of TGFβ was 2447 pg/ml but did not correlate with baseline plasma TGFβ or TTP. Conclusions: GC1008 was well tolerated in pretreated MPM patients. SD occurred in 3 pts, all with prior disease progression. Evidence for humoral anti-tumor immunity was seen in nearly half of enrollees and in 2 of 3 pts with SD. OS compares favorably to prior single-agent studies in pretreated MPM.

Final report of an open-label phase II trial of bevacizumab plus docetaxel and gemcitabine in metastatic, previously untreated nonsquamous non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18046-e18046
Author(s):  
Nathan A. Pennell ◽  
Sujith R. Kalmadi ◽  
Marc A. Shapiro ◽  
Hamed Daw ◽  
Cristina P. Rodriguez ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Nsclc ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Final Report ◽  
Hematologic Toxicity ◽  
Open Label ◽  
Open Label Phase

e18046 Background: Platinum and non-platinum doublet chemotherapy has similar efficacy in advanced NSCLC patients (pts). Bevacizumab (B) improves outcomes when added to platinum doublets, but its safety and efficacy in combination with non-platinum doublets is unknown. This study was designed to test the combination of B, docetaxel (D), and gemcitabine (G) in first-line treatment of advanced NSCLC. Methods: Pts with metastatic, non-squamous NSCLC, PS 0-1, and measurable disease by RECIST were enrolled in this open-label, single arm phase II trial. Pts received D (75 mg/m2) on d1, G (900 mg/m2) on d1 & 8, and B (15 mg/kg) on d1 every 21d for up to 6 cycles, followed by B maintenance until progression or 12 mos total. Pts received growth factor d9. CT scans were performed every 6 wks. The primary endpoint was 1-yr progression-free survival (PFS), with secondary endpoints of safety, objective response rate (ORR), overall PFS, and overall survival (OS). Pts with tumor cavitation, untreated brain metastases, and hemoptysis were excluded. Planned enrollment was 46. Results: 13 pts were enrolled from 12/2009 to 4/2011. Pt characteristics: Median age 63 (35-69), 85% male, PS 0 (38%), PS 1 (62%). The median # of cycles of chemotherapy was 6 (1-6), median # cycles of B was 4 (1-15), with 2 pts coming off study prior to the first evaluation (1 grade 5 encephalopathy, 1 grade 4 febrile neutropenia). 5 pts (38%) had chemo dose reduction and 4 (31%) discontinued treatment for toxicity. 3 pts (23%) discontinued B prior to progression, 2 for tumor cavitation and 1 for grade 1 hemoptysis. The grade 3-5 non-hematologic toxicity rate was 69%, with 6 pts (46%) hospitalized with pneumonitis/pneumonia felt possibly related to study drugs. At this point enrollment was halted for safety concerns. The 1-yr PFS was 8%, and the median PFS was 6.9 mos (95% CI 2.0-NYR). 11 pts were evaluable for response, and 6 pts had partial responses for an ORR of 55%. The median OS was NYR with median follow up of 10.9 mos. Conclusions: The combination of B, D, and G was not tolerable at the doses and schedule used in this study. A formal phase I trial is needed if this combination is to be investigated further.

A phase II trial of salvage treatment with gemcitabine and S-1 combination in heavily pretreated patients with metastatic colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3595-3595
Author(s):  
Sun Jin Sym ◽  
Junshik Hong ◽  
Hee Kyung Ahn ◽  
Jinny Park ◽  
Eun Kyung Cho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Heavily Pretreated

3595 Background: We conducted a phase II trial of gemcitabine with S-1 to evaluate the activity and toxicity of such a combination in heavily pre-treated patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after treatment with fluoropyrimidines-, oxaliplatin- and irinotecan-containing regimens. Methods: 36 pts were enrolled, with the following characteristics: 19 females (53%), median age 57 (28-72), 30 EOGO PS 0-1 (83%). S-1 was given orally (30 mg/m2) b.i.d for 14 consecutive days and gemcitabine (1000 mg/m2) was given on days 1 and 8, every 21 days, until disease progression and for a maximum of 9 cycles. The primary endpoint was objective response rate (ORR). Results: The median number of cycles was 5 (range 1-9), ORR was 16.7% (95% confidence interval [CI] 4.5-28.9%) and disease control rate was 61.1% (95% CI 45.2-77.0%) with 6 partial responses and 16 stable diseases. Median duration of disease control was 5.8 months (95% CI 4.1-7.5 months). Median progression-free survival was 3.7 months (95% CI 2.2-5.2 months) and median overall survival was 10.0 months (95% CI 7.4-12.7 months). Grade 3-4 toxicities were rare (neutropenia 12%, anemia 11%, leucopenia 6%, thrombocytopenia 3% and diarrhea 3%). Conclusions: Combination chemotherapy with gemcitabine and S-1 was a convenient, well tolerated and efficacious for heavily pre-treated pts with mCRC. This regimen warrants further evaluation in pts with good PS but no further treatment options.

A phase II trial of salvage treatment with gemcitabine and S-1 combination in heavily pretreated patients with metastatic colorectal cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 488-488 ◽  
Author(s):  
Sun Jin Sym ◽  
Junshik Hong ◽  
Hee Kyung Ahn ◽  
Jinny Park ◽  
Eun Kyung Cho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Ecog Ps

488 Background: We conducted a phase II trial of gemcitabine with S-1 to evaluate the activity and toxicity of such a combination in heavily pre-treated patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after treatment with 5-fluorouracil (5-FU), oxaliplatin and irinotecan. Methods: 34 pts were enrolled, with the following characteristics: 17 (50%) females, median age 57 years (28-72), 28 (82%) ECOG PS 0-1. S-1 was given orally (30 mg/m2) b.i.d for 14 consecutive days and gemcitabine (1000 mg/m2) was given on days 1 and 8, every 21 days, until disease progression and for a maximum of 9 cycles. The primary endpoint was objective response rate (ORR). Results: The median number of cycles was four (range 1-9). ORR was 14.7% (95% confidence interval [CI] 2.8-26.6) and disease control rate was 58.8% (95% CI 42.2-75.3) with five partial responses and fifteen stable diseases. Median duration of disease control was 5.1 months (95% CI 3.3-7.0). Median progression-free survival was 3.2 months (95% CI 2.3-4.1) and median overall survival was 11.8 months (95% CI 7.0-16.5). Grade 3-4 toxicities were neutropenia (12%), anemia (12%), thrombocytopenia (3%) and diarrhea (3%). Conclusions: Combination chemotherapy with gemcitabine and S-1 was well tolerated and efficacious for heavily pre-treated mCRC pts, and could be an alternative for pts with good PS but no further treatment options.

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