SAPPHIRE: A randomized phase II study of mFOLFOX6 + panitumumab versus 5-FU/LV + panitumumab after 6 cycles of frontline mFOLFOX6 + panitumumab in patients with colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 729-729 ◽  
Author(s):  
Masato Nakamura ◽  
Yoshinori Munemoto ◽  
Masazumi Takahashi ◽  
Masahito Kotaka ◽  
Hiroaki Kuroda ◽  
...  
Keyword(s):  
Phase Ii ◽  
Progression Free Survival ◽  
Wild Type ◽  
Primary Analysis ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Term Administration ◽  
To Receive ◽  
Clinical Trial Information

729 Background: FOLFOX therapy, an infusion of 5-fluorouracil (5-FU) with leucovorin in combination with oxaliplatin (OXA), is a common first-line chemotherapy regimen for unresectable, advanced or recurrent colorectal carcinoma (CRC). However, long-term administration of OXA is associated with peripheral neuropathy (PN); decreasing treatment length of OXA may be beneficial without reducing its efficacy. Methods: Chemotherapy-naïve pts aged ≥20 yrs with RAS wild-type advanced/recurrent CRC were enrolled to receive 6 cycles of panitumumab (Pmab) + mFOLFOX6 once every 2 wks. Pts who completed 6 cycles of Pmab + mFOLFOX6 and confirmed no progressive disease were subsequently randomized 1:1 to continue to receive Pmab + mFOLFOX6 (arm 1) or Pmab + 5-FU/LV (arm 2). The primary endpoint was progression-free survival (PFS) rate at 9 mos after randomization. The threshold PFS rate was defined as 30%, and the expected rate was set at 50%, with a 90% power and a 1-sided alpha value of 0.10. In the primary analysis, a binomial test was conducted separately for each arm. This study was designed as a phase II randomized screening comparison study which does not use direct comparison for the primary analysis. Results: Of 164 enrolled pts who received initial Pmab + mFOLFOX6 treatment, 56 were randomized to arm 1 and 57 to arm 2. PFS rates at 9 mos after randomization were significantly higher than the defined threshold at 44.6% (80% CI, 36.4–53.2) in arm 1 and 47.4% (39.1–55.8) in arm 2. Median PFS after randomization was 9.1 (8.6–11.2) and 9.3 (6.0–13.0) mos, respectively. Grade ≥2 PNs occurred in 6 (10.7%) and 1 (1.8%) pts in arms 1 and 2, respectively. Serious AEs occurred in 14 (25.0%) pts in arm 1 and in 9 (16.7%) pts in arm 2. Conclusions: The results of this trial suggest that Pmab + 5-FU/LV after 6 fixed-cycles of Pmab + mFOLFOX6 may be a treatment option in pts with RAS wild type chemotherapy-naïve advanced/recurrent CRC. Pts treated with Pmab + 5-FU/LV had a lower occurrence of grade ≥2 PNs compared with Pmab + mFOLFOX6. Clinical trial information: NCT02337946.

Analysis of KRAS/NRAS mutations in PEAK: A randomized phase II study of FOLFOX6 plus panitumumab (pmab) or bevacizumab (bev) as first-line treatment (tx) for wild-type (WT) KRAS (exon 2) metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3631-3631 ◽  
Author(s):  
Lee Steven Schwartzberg ◽  
Fernando Rivera ◽  
Meinolf Karthaus ◽  
Gianpiero Fasola ◽  
Jean-Luc Canon ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Progression Free Survival ◽  
Primary Analysis ◽  
Exon 2 ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Exon 4 ◽  
Grade 3 ◽  
Kras Exon ◽  
Clinical Trial Information

3631 Background: PEAK estimated the tx effect of FOLFOX6 with pmab or bev in 1st-line WT KRAS mCRC. The PRIME study showed significantly improved progression free survival (PFS) and overall survival (OS) with pmab + FOLFOX vs FOLFOX in pts with WT RAS (KRAS/NRAS exons 2, 3, 4) mCRC in a prospective-retrospective analysis (unpublished data). Methods: This prospective-retrospective analysis of PEAK was designed to assess the effect of pmab + FOLFOX6 or bev + FOLFOX6 on PFS (primary endpoint) and OS in WT RAS (KRAS/NRAS exons 2, 3, 4) mCRC. Pts were required to have WT KRAS exon 2 tumors. Bidirectional Sanger sequencing and Transgenomic SURVEYOR/WAVE analysis were independently conducted to detect mutations in KRAS exon 3 (codons 59/61), exon 4 (codons 117/146); NRAS exon 2 (codons 12/13), exon 3 (codons 59/61), exon 4 (codons 117/146); BRAF exon 15 (codon 600) in banked specimens. Results: 285 WT KRAS (exon 2) mCRC patients (pts) were randomized, 278 received tx. The current RAS ascertainment rate is 75%. Tx HRs (pmab:bev) for pts with WT RAS were 0.63 (95% CI, 0.43-0.94; p = 0.02) for PFS and 0.55 (95% CI, 0.30-1.01; p = 0.06) for OS (Table). The incidence of worst grade 3-5 adverse events was consistent with the primary analysis. Updated OS and BRAF results will be presented. Conclusions: In this 1st-line estimation study in WT RAS mCRC, PFS and OS HR favored pmab + FOLFOX6 relative to bev + FOLFOX6, suggesting that activating RAS mutations appear to be predictive for pmab tx effect. The safety profile for both arms was consistent with previously reported studies. Clinical trial information: NCT00819780. [Table: see text]

PARTNER: A randomized phase II study of docetaxel/cisplatin (doc/cis) chemotherapy with or without panitumumab (pmab) as first-line treatment (tx) for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6029-6029 ◽  
Author(s):  
Lori J. Wirth ◽  
Shaker R. Dakhil ◽  
Gabriela Kornek ◽  
Rita Axelrod ◽  
Douglas Adkins ◽  
...  
Keyword(s):  
Phase Ii ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Hpv Status ◽  
Secondary Endpoints ◽  
Baseline Characteristics ◽  
Grade 3 ◽  
Clinical Trial Information

6029 Background: PARTNER was a multicenter, randomized phase II estimation study evaluating 1stEline tx of R/M SCCHN with doc/cis ± pmab. Methods: Patients (pts) were randomized 1:1 to doc/cis with pmab (Arm 1) or doc/cis alone (Arm 2). Arm 1 received 9 mg/kg pmab on day 1 of each 21-day cycle, and all pts received 1stEline doc/cis both at 75 mg/m2 on day 1 for up to 6 cycles. In Arm 1, pts could receive pmab monotherapy upon completion of 6 cycles of doc/cis until disease progression (PD). In Arm 2, pts could receive pmab as 2ndEline monotherapy upon PD. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. HPV status was determined using p16 INK IHC. No formal hypothesis was tested. Results: Baseline characteristics were balanced between arms. Of 103 pts, HPV status was evaluable in 66 (64%); 29% were HPV positive. Efficacy results are shown (Table). Worst grade 3/4 adverse events (AEs) were 73% in Arm 1 vs 56% in Arm 2. Conclusions: Median PFS was increased in both arms over historical doublet cytotoxic chemotherapy. PFS and ORR were higher in the pmab arm in the overall population, in the HPV positive (n=19) group, and in the HPV negative (n=47) group. There was an increase in grade 3/4 AEs with this regimen. The crossover design, with 57% of Arm 2 pts receiving pmab as 2ndEline monotherapy, confounds interpretation of OS. Clinical trial information: NCT00454779. [Table: see text]

A randomized phase II trial of gemcitabine plus treosulfan versus treosulfan alone in patients with metastatic uveal melanoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8018-8018
Author(s):  
A. H. Schmittel ◽  
M. Schmidt-Hieber ◽  
N. E. Bechrakis ◽  
R. Schuster ◽  
J. M. Siehl ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Phase Ii ◽  
Randomized Trials ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Melanoma Patients ◽  
To Receive

8018 Background: In-vitro studies have suggested synergy of gemcitabine and treosulfan against uveal melanoma cells, and the combination of both drugs in the GeT regimen has shown activity in metastatic uveal melanoma patients. This first randomized phase II trial in this rare disease compared the efficacy of the gemcitabine/treosulfan (GeT) combination versus treosulfan alone. Methods: Chemotherapy-naïve patients with proven metastatic uveal melanoma were randomly assigned to receive 1000mg/m2 gemcitabine plus 3500mg/m2 of treosulfan (GeT) or 3500mg/m2 of treosulfan (T) alone. Chemotherapy was administered on days 1 and 8 in both arms, cycles were repeated on day 29. In the absence of disease progression a maximum of 6 cycles were administered. Results: Forty-eight patients were randomized. Seven confirmed stable diseases and one partial remission were observed in 24 patients (PR+SD=33%) treated with the GeT regimen, whereas no PR and only 3 SD (13%) were observed in the treosulfan alone arm (p=0.08). Median progression free survival was 3 months (95% CI 1.1–4.9) in the GeT arm and 2 months (95% CI interval 1.7–2.3) in the treosulfan arm (p=0.008, log-rank). Six and 12 months progression free survival was 34.8% and 17.9% and 16.7% and 0% always favouring the GeT arm. Conclusions: This first prospectively randomized trial in metastatic uveal melanoma showed a superior PFS and a trend for a higher response/stabilization rate of the GeT combination over treosulfan alone. Therefore GeT will further be investigated in randomized trials. No significant financial relationships to disclose.

Randomized phase II trial of NGR-hTNF in combination with standard chemotherapy in previously untreated non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8035-8035
Author(s):  
Vanesa Gregorc ◽  
Nicoletta Zilembo ◽  
Francesco Grossi ◽  
Tommaso M De Pas ◽  
Gilda Rossoni ◽  
...  
Keyword(s):  
Synergistic Effects ◽  
Pulmonary Hemorrhage ◽  
Progression Free Survival ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Baseline Characteristics ◽  
Grade 3 ◽  
To Receive ◽  
Clinical Trial Information

8035 Background: NGR-hTNF, a selective antivascular agent, induces at low dose an initial vascular normalization that greatly enhances the intratumoral chemotherapy uptake, with synergistic effects that were noted especially in combination with cisplatin and gemcitabine. Methods: Chemo-naive patients (pts) with advanced NSCLC were stratified by histology (nonsquamous or squamous) and PS (0 or 1) and randomly assigned to receive cisplatin 80 mg/m2/d1 plus either pemetrexed 500 mg/m2/d1 (nonsquamous) or gemcitabine 1,250 mg/m2/d1+8 (squamous) every 3 weeks (q3w) for 6 cycles, with (arm A) or without (arm B) NGR-hTNF given at 0.8 μg/m2/d1/q3w until progression. Progression-free survival (PFS) was primary aim (1-β=80%, 1-sided α=10%, n=102). Secondary aims comprised adverse events (AEs), response rate (RR), and overall survival (OS). Results: Baseline characteristics in arm A (n=62) vs B (n=59) were: median age: 62 vs 63 years; men: 37 vs 39; PS 1: 23 vs 23; squamous: 18 v 17; smokers: 41 vs 43. For the nonsquamous stratum, 299 cycles were given in arm A (mean 7.0; range 1-20) and 192 in arm B (4.8; 1-6), while for the squamous stratum, 113 in arm A (6.7; 1-31) and 52 in arm B (3.5; 1-6). Rates of grade 3/4 AEs were similar (arm A vs B): neutropenia 13% vs 18%, anaemia 7% vs 4% and fatigue 7% vs 11%. No grade 3/4 AEs related to NGR-hTNF or bleeding/pulmonary hemorrhage events were reported in the squamous subset. With median follow-up time of 24.2 months, median PFS (5.8 vs 5.6 months; HR=0.92), RR (25% vs 21%) and 1-year OS (53% vs 53%) were similar between the two treatment arms. However, by predefined analysis in the squamous stratum, median PFS was 5.6 months for arm A and 4.3 months for arm B (hazard ratio, HR=0.75) and median OS was 14.2 months for arm A and 9.7 months for arm B (HR=0.49; p=0.07). In pts with squamous histology, RR was 38% for arm A and 27% for arm B (odds ratio=1.6), while the median changes in tumor size on treatment from baseline to 2nd, 4th and 6th cycle for arm A vs B were -32% vs -20%, -41% vs -19%, and -42% vs -14%, respectively. Conclusions: Clinical tolerability and benefit were noted in squamous NSCLC with NGR-hTNF plus cisplatin and gemcitabine, which deserve further investigation. Clinical trial information: NCT00994097.

Prevalence and outcomes of patients (pts) with EGFR S492R ectodomain mutations in ASPECCT: Panitumumab (pmab) vs. cetuximab (cmab) in pts with chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer (mCRC).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 740-740 ◽  
Author(s):  
Timothy Jay Price ◽  
Kathryn Newhall ◽  
Marc Peeters ◽  
Tae Won Kim ◽  
Jin Li ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Wild Type ◽  
Exon 2 ◽  
Free Survival ◽  
Droplet Pcr ◽  
Secondary Endpoints ◽  
To Receive ◽  
Clinical Trial Information

740 Background: Mutations resistant to anti-EGFR treatment (tx), beyond those in RAS, have been reported and include EGFR S492R. We report results for pts with EGFR S492R mutations in the phase 3 ASPECCT trial. Methods: Pts were randomized 1:1 to receive pmab or cmab. Crossover was not allowed. The primary endpoint was non-inferiority of overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. EGFR S492R was evaluated by digital droplet PCR in plasma samples collected pre-tx and post-tx (safety follow-up 4 wks after the last dose). Outcomes were analyzed by EGFR S492 status. Results: Of 999 pts randomized and treated, post-tx samples were available for EGFR S492 assessment from 53% of pts (261/496) in the pmab arm and 57% of pts (285/503) in the cmab arm. EGFR S492R was detected in 1% of pts in the pmab arm and 16% of pts in the cmab arm in post-tx samples. EGFR S492R was not detected in pre-tx samples. Results are shown (table). Conclusions: In a retrospective analysis of pts with available samples from ASPECCT, 16% of pts in the cmab arm and 1% of pts in the pmab developed EGFR S492R mutations. Pts with EGFR S492R in the cmab arm had longer tx duration before progressive disease (PD) and appeared to have worse OS vs pts with wild-type S492 in the cmab arm. Clinical trial information: NCT01001377. [Table: see text]

Exploratory phase II evaluation of cabozantinib in recurrent/metastatic uterine carcinosarcoma (CS): A study of the Princess Margaret, Chicago, and California phase II consortia.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5587-5587
Author(s):  
Victoria Mandilaras ◽  
Neesha C. Dhani ◽  
Qian Tan ◽  
Angela Jain ◽  
Carolyn Johnston ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Molecular Data ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Platinum Based Chemotherapy ◽  
Clinical Trial Information ◽  
Aggressive Subtype ◽  
Mutation Profiling

5587 Background: Carcinosarcoma (CS) is a rare ( < 5%) aggressive subtype of endometrial cancer (EC). Patients (pts) with progression on platinum-based chemotherapy (CTX) have limited options, there is no standard 2ndline treatment and median progression-free survival (PFS) is < 2months (mt), 6-mt PFS less than 20%. Limited molecular data on CS aligns with epithelial EC, providing rationale for evaluating similar strategies such as targeting MET and angiogenesis. Cabozantinib (cabo) is multi-targeted tyrosine kinase inhibitor against MET, VEGFR, TIE2, RET, AXL and KIT. Methods: PHL-86 (NCI#9322/NCT01935934) is a multi-centre, non-randomized, phase II trial of cabo (60 mg oral daily dose on a 28-day cycle) in EC pts recurring within a year of adjuvant CTX or with progression after 1stline of CTX for metastatic disease. Pts with rare histology including CS, were enrolled in an exploratory cohort. Activity of interest for further evaluation was defined as 4 responses (either partial response [PR] or 12-wk PFS) out of 10 pts of a given histotype. CT scans were performed after cycle 3 and every 2 cycles thereafter. Results: From 2013 to 2016, 32 pts were treated in the exploratory cohort, 19 pts with CS. Median age was 66 years (range 25-75); prior treatment included CTX (17: 1 line, 6: 2 lines) and/or radiation (11). Fifteen pts were evaluable for response, with 1 PR (7%) and 8 pts with 12-wk PFS (53%). Median PFS was 3 mt (95% CI: 2.7 – 4.6) with estimated 6-mt PFS of 13% (2 to 33%). Toxicity evaluation is available for 19 pts. Common events were fatigue and GI upset. Most frequent > Grade3 toxicities were hypertension (5), anemia (4), diarrhea (2). Four pts had GI fistula (2) or perforation (2). Mutation profiling in archival tissue showed TP53 (73%), PIK3CA (40%), KRAS (27%), PTEN(13%) with > 1 mutation present in 14/15 pts analyzed. The 1 pt with no somatic mutations had a PR (31% decrease) on cabo (PFS 6.7mt). Conclusions: Cabo in CS cohort met the predefined endpoint for further evaluation and compares favourably with other agents in this poor prognosis disease. Larger studies are required to define depth and durability of response and identify relevant biomarkers. Clinical trial information: NCT01935934.

A randomized phase II study comparing oral S-1 plus 24-hour infusion of irinotecan (Iri) and bevacizumab (Bev) with FOLFIRI plus bevacizumab in patients with metastatic colorectal cancer (MCRC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 613-613
Author(s):  
Sotaro Sadahiro ◽  
Toshiyuki Suzuki ◽  
Akira Tanaka ◽  
Kazutake Okada ◽  
Gota Saito ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
To Receive ◽  
First Line Treatment

613 Background: FOLFOX or FOLFIRI plus Bev is a first-line treatment for MCRC. Recent studies have confirmed that oral S-1 combined with Iri and Bev is equivalent to FOLFIRI plus Bev. Iri is usually administered as a short-term 90-min. infusion. However, the cytocidal activity is S-phase specific, and carboxylesterases, that convert Iri into SN-38, are less likely to become saturated when Iri is given as a long-term infusion. Therefore, a low dose of Iri given as a long-term infusion is expected to enhance antitumor activity. We conducted a randomized phase II study to compare this regimen with FOLFIRI plus Bev. Methods: The subjects comprised 120 chemotherapy-naïve patients with MCRC. The study group received 24-hr infusion of Iri at a dose of 125 mg/m2 on days 1 and 15, combined with oral S-1 80 mg/m2 on days 1 to 14. The FOLFIRI group received Iri at a dose of 150 mg/m2, 5-FU given at a dose of 400 mg/m2 as a bolus injection and at a dose of 2400 mg/m2 as a 46 hr-infusion, 200 mg/m2 of leucovorin on days 1 and 15. Bev was given at a dose of 5.0 mg/kg on days 1 and 15 in both groups. Treatment was repeated every 4 weeks. The primary endpoint was the 1 y progression-free survival (PFS). Secondary endpoints were PFS, response rates (RR), overall survival (OS), and adverse events (AEs). Results: From October 2013 through December 2017, a total of 61 patients assigned to receive IRIS plus Bev (the A group) and 59 patients assigned to receive FOLFIRI plus Bev (the B group) were included in the analysis. The 1y RFS was 37.3% in the A group and 17.0% in the B group (p = 0.0281). The PFS was 10.2 mon in the A group and 10.0 mon in the B group, and the median OS was 27.0 mon and 28.6 mon, respectively (p = 0.26, p = 0.68). RR was significantly higher in the A group (87.0%) than in the B group (61.7%) (p = 0.005). The main grade 3 or 4 AEs were neutropenia (27.8%) and diarrhea (11.1%) in the A group and neutropenia (23.4%) and leukopenia (6.4%) in the B group. Conclusions: Our results showed that Iri, given biweekly as a 24-hour infusion in combination with oral S-1 and Bev, is a highly effective and well-tolerated regimen for the first-line treatment of MCRC. Clinical trial information: UMIN000014664.

An Increasing Role for Trabectedin in Gynecological Cancers: Efficacy in Uterine Sarcomas

2011 ◽  
Vol 21 (Supp 1) ◽  
pp. S3-S5 ◽  
Author(s):  
Isabelle Ray-Coquard
Keyword(s):  
Phase Ii ◽  
Progression Free Survival ◽  
Uterine Leiomyosarcoma ◽  
Uterine Sarcomas ◽  
Free Survival ◽  
Phase Ii Studies ◽  
Prospective Phase ◽  
Pretreated Patients ◽  
To Receive ◽  
A Current

Trabectedin is indicated for patients with advanced soft tissue sarcoma after failure of treatment with anthracyclines and ifosfamide or for patients who are unsuited to receive these agents. The agent has shown activity in patients with advanced uterine leiomyosarcoma, with an acceptable safety profile. Thus, the results of phase II studies have shown that treatment with trabectedin results in 30% progression-free survival at 6 months. More than 50% of these pretreated patients were alive at 1 year. The response rate, progression-free survival, and overall survival compared favorably with other single agents (eg, doxorubicin, ifosfamide, and gemcitabine), with clinical benefit in 50% of patients in second-line treatment. These results are being confirmed in a current prospective phase II study in first-line uterine leiomyosarcoma combining trabectedin with doxorubicin.

scholarly journals Randomized Phase II Study of SOX+B-mab Versus SOX+C-mab in Patients With Previously Untreated Recurrent Advanced Colorectal Cancer With Wild-Type KRAS (MCSGO-1107 Study)

2021 ◽  
Author(s):  
Yujiro Nishizawa ◽  
Naotsugu Haraguchi ◽  
Hirotoshi Kim ◽  
Yoshihito Ide ◽  
Ken Nakata ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Wild Type ◽  
Open Label ◽  
Randomized Phase Ii ◽  
Early Tumor ◽  
Patient Prognosis ◽  
Clinical Trials Registry

Abstract Background: Although chemotherapy for metastatic colorectal cancer (mCRC) has improved, the standard chemotherapy regimens for patients with RAS wild-type mCRC remain debated.Methods: This randomized phase II, open-label, multicenter study compared the efficacy and safety of S-1 and oxaliplatin (SOX)+bevacizumab (B-mab) with SOX+cetuximab (C-mab) in patients with previously untreated recurrent advanced CRC with wild-type KRAS. Between February 2012 and October 2016, 45 patients were enrolled.Results: Overall response rates were 59.1% and 43.5% (p=0.29) and disease control rates were 90.9% and 91.3% (p=0.96) in the SOX+B-mab and SOX+C-mab groups, respectively. Median overall survival (OS) was 25.3 and 15.5 months (HR=0.607, p=0.167) and median progression-free survival (PFS) were 11.7 and 5.5 months (HR=0.558, p=0.077) in the SOX+B-mab and SOX+C-mab groups, respectively. The OS and PFS of patients with early tumor shrinkage (ETS) were not significantly different in the SOX+B-mab group. However, they were significantly better when ETS was ≥20 in the SOX+C-mab group (p=0.032 and p=0.003, respectively).Conclusions: The efficacy and safety of SOX+B-mab and SOX+C-mab for wild-type KRAS recurrent advanced CRC as first-line chemotherapy were almost the same. Consideration of the treatment strategy based on ETS may improve patient prognosis, especially in patients receiving the SOX+C-mab regimen.Trial registration: UMIN Clinical Trials Registry (UMIN000006706)Date of registration: NOV/11/2011URL of trial registry record:https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000007920

PULSE: A randomized phase II open label study of panitumumab rechallenge versus standard therapy after progression on anti-EGFR therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS143-TPS143
Author(s):  
John H. Strickler ◽  
Fang-Shu Ou ◽  
Tanios S. Bekaii-Saab ◽  
Christine Megerdichian Parseghian ◽  
Andrea Cercek ◽  
...  
Keyword(s):  
Phase Ii ◽  
Clinical Benefit ◽  
Objective Response ◽  
Progression Free Survival ◽  
Wild Type ◽  
Open Label ◽  
Genomic Alterations ◽  
Open Label Study ◽  
Label Study ◽  
Randomized Phase Ii

TPS143 Background: Patients with KRAS and NRAS ( RAS) wild-type mCRC benefit from the epidermal growth factor receptor (EGFR) monoclonal antibodies (Abs) panitumumab and cetuximab, but nearly all patients experience resistance. Blood-based profiling of cell free DNA (cfDNA) can identify genomic alterations that drive acquired EGFR Ab resistance. After discontinuation of anti-EGFR Abs, acquired genomic alterations decay over time to undetectable levels. Some studies have suggested clinical benefit from EGFR Ab rechallenge, but there is limited evidence that EGFR Ab rechallenge improves survival compared to standard of care (SOC) therapies. We hypothesize that cfDNA profiling will identify patients appropriate for panitumumab rechallenge, and that these molecularly selected patients will have improved survival compared to current SOC therapies. Methods: This is a randomized phase II, open label study designed to compare the overall survival (OS) of panitumumab rechallenge versus SOC (investigator choice TAS-102 or regorafenib). Secondary objectives include comparisons of progression free survival, objective response rate, clinical benefit rate, and quality of life as measured by the linear analogue self-assessment (LASA) questionnaire. Eligible patients have radiographically measurable KRAS, NRAS, and BRAF codon 600 wild-type mCRC based on tumor tissue testing, and must have experienced progression or intolerance to treatment with a fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF Ab, and an anti-PD-1 Ab if the tumor has mismatch repair deficiency or is MSI-H. Progression after at least 4 months treatment with an anti-EGFR Ab is required. All patients must be enrolled in the COLOMATE cfDNA screening protocol (NCT03765736) and meet molecular eligibility based on Guardant360 cfDNA profiling (absence of amplification of ERBB2, KRAS, NRAS, and MET; absence of mutations of BRAF, EGFR, ERBB2, KRAS, NRAS, and MET [mutant allele frequency > 0.5%]). Greater than 90 days must have elapsed between the most recent treatment with an anti-EGFR Ab and cfDNA profiling. Dosing for all study drugs is according to clinical SOC. 120 patients will be randomized 1:1 to panitumumab rechallenge or SOC. With 83 OS events, this study will have 80% power to detect an improvement in median OS from 6.5 to 10 months (HR=0.65; 1-sided α= 0.15). This study began enrollment in 6/2020. Recruitment is ongoing at 16 sites in the Academic and Community Cancer Research United (ACCRU) network (ACCRU-GI-1623). Clinical trial information: NCT03992456.

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