Phase II study of the anti-ganglioside GD3 mouse/human chimeric antibody KW2871 combined with high dose interferon-a2b in patients with metastatic melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8547-8547
Author(s):  
Stergios J. Moschos ◽  
Ahmad A. Tarhini ◽  
Thomas Gajewski ◽  
Andrew Mark Scott ◽  
Yan Lin ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Phase Ii ◽  
Immune Cells ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Chimeric Antibody ◽  
High Dose ◽  
Open Label

8547 Background: Immunotherapy has demonstrated notable effects in metastatic melanoma (MM) with durable responses achieved by high-dose IL-2 and IFNα2b, leading to approval of these therapies for treatment of melanoma. However, complete responses occur in only a minority of patients. KW2871 is a chimeric monoclonal antibody (mAb) targeting the GD3 ganglioside with demonstrated antitumor activity and enhancement of antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). IFNα2b has potent immunoregulatory, anti-proliferative, differentiation-inducing, pro-apoptotic, and anti-angiogenic properties against a variety of malignancies including melanoma. Combining high dose IFNα2b (HDI) + KW2871 was hypothesized to have synergistic anti-tumor activity due to (1) the ability of HDI to enhance KW2871 induced ADCC in vitro (Liu, Cancer Immun 2002); (2) improved mAb targeting due to increased GD3 expression and induced inflammatory cytokines (TNF-α, IL-4 and IFN-γ) (Hoon, Cancer Res, 1991); (3) increased tumor-infiltrating immune cells (Kirkwood, Cancer 2002; Moschos, J Clin Oncol 2006). Methods: This is an open label, dose-escalation, phase II study of KW2871 plus HDI in patients with measurable MM. Primary objectives are progression-free survival (PFS) and safety. Secondary objectives include assessment for tumor response by RECIST, ADCC, CDC, pharmacokinetics, human antichimeric antibodies (HACA), tumor-infiltrating immune cells, biomarkers and OS. Patients with measurable disease by RECIST, stable brain metastases, and performance status ECOG 0 or 1 are eligible. Patients with severe comorbidities or autoimmune disease or prior exposure to anti-GD3 antibodies are excluded. Sequential enrollment to cohorts of KW2871 at 5, 10 , 20 mg/m2 IV every 2 week in combination with HDI 20 MU/m2 IV once daily x 5 Days for 4 weeks, then 10 MU/m2 SC three times weekly until disease progression. Results: To date, Cohort 1 (5 mg/m2 KW2871) and Cohort 2 (10 mg/m2 KW2871) have been completed safely. Cohort 3 (20 mg/m2 KW2871) has enrolled of 18 of 27 planned patients. Conclusions: Will be presented at study completion.

Phase II study of combination therapy with S-1 and cetuximab in patients with KRAS wild-type unresectable colorectal cancer who had previously received irinotecan, oxaliplatin, and fluoropyrimidines (KSCC0901).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3558-3558
Author(s):  
Kazuma Kobayashi ◽  
Yasunori Emi ◽  
Yoshihiro Kakeji ◽  
Takao Takahashi ◽  
Eiji Oki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Combination Therapy ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Dihydropyrimidine Dehydrogenase ◽  
Treatment Protocol ◽  
Progression Free Survival ◽  
Wild Type ◽  
Open Label

3558 Background: Anti-epidermal growth factor receptor (anti-EGFR) antibodies alone or in combination with irinotecan (Iri) can be considered standard third-line therapy for KRAS wild-type (wKRAS) unresectable colorectal cancer (UNCRC). However, some UNCRC patients (pts) cannot tolerate Iri-containing therapy. S-1, an oral fluorouracil (FU) derivative, enhances the anti-tumor effect by inhibiting dihydropyrimidine dehydrogenase activity and reducing digestive toxicity. Combination therapy with cetuximab (C-mab) may restore 5-FU resistance in 5-FU–resistant CCs. Therefore, we examined the efficacy of S-1+C-mab therapy in wKRAS UNCRC pts, who had previously received Iri, oxaliplatin (OX), and FUs. Methods: The study design was multicenter, single-arm, open-label phase II study. The major inclusion criteria were written informed consent; histologically proven CRC and clinically proven UNCRC; presence of measurable lesions; previous therapy with Iri, OX, and 5-FU; documented progressive disease after 5-FU–based chemotherapy; wKRAS tumors; age ≥ 20 years; performance status (PS) 0–1; and adequate organ function. The treatment protocol was as follows: weekly durable intravenous (DIV) C-mab administration at 400 mg/m2 (day 1) and 250 mg/m2/week (except day 1) and oral administration of 80 mg/m2/day S-1 on days 1–28 of each 42-day cycle. The primary endpoint was progression-free survival (PFS). A sample size of 39 was planned for a threshold PFS of 3.5 months and expected value of 6.0 months, with one-sided alpha of 0.05 and beta of approximately 0.2. Results: One patient was ineligible; 38 pts (PS 0/1, 32/6; 1/2/>3 prior chemotherapy regimens, 4/23/11) were enrolled from 10/2009 to 12/2010. The median PFS (central review) was 5.5 months (90% CI: 4.4 – 5.7); median overall survival (OS), 13.1 months; and the best ORR, 36.8%. The most common grade 3–4 adverse events were neutrophils, hypokalemia, rash, and dry skin. Conclusions: This study showed that S-1+C-mab may be a promising and well-tolerated treatment choice of wKRAS UNCRC, who had previously heavily treated by Iri, OX and FUs.

Multicenter, open-label phase II study of daily oral regorafenib for chemotherapy-refractory, metastatic and locally advanced angiosarcoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11561-11561
Author(s):  
Mark Agulnik ◽  
Steven Ian Robinson ◽  
Scott H. Okuno ◽  
Brittany Siontis ◽  
Steven Attia ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Study ◽  
Performance Status ◽  
Locally Advanced ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Open Label ◽  
Tie2 Receptor ◽  
Open Label Phase

11561 Background: Angiosarcoma has a particularly poor prognosis with 5-year overall survival rates of approximately 30-40%. Treatment of locally advanced and metastatic angiosarcoma is inadequate. Data strongly suggest concurrent, potent inhibition of VEGFR and Tie2 represents an attractive therapeutic strategy in angiosarcoma. Regorafenib displays potent VEGFR and Tie2 receptor inhibition and also possesses activity against additional potential targets in angiosarcoma including PDGFRs, RAF, KIT and FGFR, amongst others. Methods: A multicenter phase II study of regorafenib in patients with locally advanced or metastatic angiosarcoma was conducted through the Midwest Sarcoma Trials Partnership. Adequate performance status, organ function, measurable disease (RECIST 1.1) and 1-4 prior therapies were required. Regorafenib 160 mg PO daily was given in 28-day cycles (21 days on, 7 days off) until disease progression (PD) or unacceptable toxicity. The primary endpoint was progression-free survival (PFS), assessed at 16 weeks. Secondary endpoints include overall response rate (ORR), clinical benefit rate (CBR), OS, and safety and tolerability. A Simon 2-stage design was used. Results: After final enrollment of the second stage, a total of 31 pts were enrolled at 6 sites, 23 are evaluable for response. Median age was 65 (range 30-91); 50% were female, 67.7% had metastatic disease. PFS at 4 months is 52.2% with a median PFS and OS of 3.55 and 11.4 months. 1 confirmed CR and 2 PR, 12 SD and 8 PD were observed. ORR and CBR are 14.29 and 65.2%, respectively. No uncommon grade 3-4 adverse events were observed. 6 pts were non-evaluable due to refusal of further therapy and 2 patients progressed prior to first evaluation. Conclusions: Regorafenib was well tolerated in this study of pretreated patients with angiosarcomas and met its primary endpoint with a median PFS > 45% at 4 months. Treatment was feasible and did not reveal any previously unreported toxicities. Efficacy outcomes were complicated by early withdrawals of patients. RECIST responses were encouraging and regorafenib has a clinically meaningful 4-month PFS. Clinical trial information: NCT02048722 .

A phase II study of high-dose continuous infusion interleukin-2 with lymphokine-activated killer cells in patients with metastatic melanoma.

1991 ◽  
Vol 9 (4) ◽  
pp. 641-648 ◽  
Author(s):  
J P Dutcher ◽  
E R Gaynor ◽  
D H Boldt ◽  
J H Doroshow ◽  
M H Bar ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Metastatic Melanoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Interleukin 2 ◽  
Lak Cells ◽  
High Dose ◽  
Lymphokine Activated Killer Cells ◽  
Lak Cell

Thirty-three patients with metastatic melanoma were treated in a phase II study with an intravenous continuous infusion (IVCI) of interleukin-2 (IL2) given with lymphokine-activated killer (LAK) cells. The dose of IL2 was the optimal priming dose for LAK-cell induction, followed by the maximally tolerated LAK-cell dose that could be given by an IVCI schedule as determined by a previous phase I trial. The CI schedule was chosen for evaluation because of a postulated reduction in toxicity with the possibility of administering a more prolonged IL2 infusion and because greater rebound lymphocytosis and LAK-cell generation had been reported using this dose and schedule. The 33 patients were similar in age, performance status, and sites of disease to those treated in previous IL2 trials. All patients were assessable for response and toxicity. One patient (3%) achieved a partial response of 10 months duration. There were no other clinically significant responses. Significant toxicity included hypotension requiring pressors (45%), dyspnea (36%), renal insufficiency (24%), hepatic dysfunction (66%), and cardiac arrhythmias (18%). These toxicities reversed with cessation of the infusion. There were four deaths during the first 30 days of treatment, three from infection (one related to central line, one related to LAK cells, one related to tumor), and one from tumor-related hemorrhage. Toxicity was unexpectedly high and at least comparable to that seen in previous studies using a high-dose IV bolus schedule of IL2. When comparing the IVCI schedule with high-dose bolus IL2 to LAK cells in nonrandomized but sequential studies in patients with advanced melanoma, it appears that CI IL2 is less efficacious.

First-Line Chemotherapy With Cisplatin Plus Fractionated Temozolomide in Recurrent Glioblastoma Multiforme: A Phase II Study of the Gruppo Italiano Cooperativo di Neuro-Oncologia

2004 ◽  
Vol 22 (9) ◽  
pp. 1598-1604 ◽  
Author(s):  
Alba A. Brandes ◽  
Umberto Basso ◽  
Michele Reni ◽  
Francesca Vastola ◽  
Alicia Tosoni ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Hematologic Toxicity ◽  
Recurrent Glioblastoma Multiforme

Purpose Cisplatin and temozolomide (TMZ) are active in glioblastoma multiforme (GBM), with different profiles of toxicity. A bid regimen of TMZ achieves a strong inhibition of O6-alkylguanine DNA-alkyl transferase (AGAT), and cisplatin reduces AGAT activity in vitro, suggesting a possible synergic interaction. The primary end point of the present multicenter phase II study was progression-free survival (PFS) at 6 months (PFS-6); secondary end points included response, toxicity, and overall survival. Patients and Methods Chemotherapy-naive patients with GBM who experienced disease recurrence or progression after surgery and standard radiotherapy were eligible. Chemotherapy cycles consisted of cisplatin 75 mg/m2 on day 1, TMZ 130 mg/m2 bolus followed by nine doses of 70 mg/m2 every 12 hours (total of 5 days) from day 2 every 4 weeks. In the absence of hematologic toxicity, TMZ was escalated to 1,000 mg/m2 in 5 days. Results A total of 50 patients (median age, 53.4 years; range, 27 to 70 years; median Karnofsky performance status, 80; range, 60 to 100) were accrued in the study. PFS-6 was 34% (95% CI, 23% to 50%), and PFS-12 was 4% (95% CI, 0.3% to 16%). Median PFS was 18.4 weeks (95% CI, 13 to 25.9 weeks). Among 49 assessable patients, one complete response and nine partial responses were obtained, with an overall response rate of 20.4% (95% CI, 7.7% to 33%). Among 203 treatment cycles delivered, the most common grade 3 or grade 4 events included granulocytopenia in 7.9% of cycles, thrombocytopenia in 4%, and neurologic toxicity in three patients (6%). Conclusion The new cisplatin plus bid TMZ regimen appears active in chemotherapy-naive patients with recurrent GBM and incurs an acceptable toxicity.

scholarly journals Phase II study of metronomic treatment with daily oral vinorelbine as first-line chemotherapy in patients with advanced/metastatic HR+/HER2− breast cancer resistant to endocrine therapy: VinoMetro—AGO-B-046

2021 ◽  
Author(s):  
Slavomir Krajnak ◽  
Thomas Decker ◽  
Lukas Schollenberger ◽  
Christian Rosé ◽  
Christian Ruckes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Open Label ◽  
Oral Vinorelbine ◽  
Her2 Breast Cancer ◽  
Line Chemotherapy

Abstract Purpose Metronomic chemotherapy (MCT) is an increasingly used treatment option in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced/metastatic breast cancer (MBC) after failure of endocrine-based therapies. Methods VinoMetro was a multicentre, open-label, single-arm, phase II study of metronomic oral vinorelbine (VRL; 30 mg/day) as a first-line chemotherapy (CT) in patients with HR+/HER2− MBC after endocrine failure. The primary endpoint was the clinical benefit rate (CBR) at 24 weeks. Results Between January 2017 and April 2019, nine patients were enrolled. The CBR was 22.2% (90% confidence interval [CI] 4.1–55.0), p = 0.211. The median progression-free survival (PFS) was 12.0 weeks (95% CI 11.3–12.7). Grade 3–4 adverse events (AEs) occurred in 22.2% of patients. One patient died of febrile neutropenia. Conclusion VinoMetro (AGO-B-046) was closed early after nine patients and occurrence of one grade 5 toxicity in agreement with the lead institutional review board (IRB). Metronomic dosing of oral VRL in HR+/HER2− MBC as first-line CT after failure of endocrine therapies showed only limited benefit in this population. Trial registration number and date of registration ClinicalTrials.gov Identifier: NCT03007992; December 15, 2016.

scholarly journals Oral vinorelbine and cisplatin as first-line therapy for advanced squamous NSCLC patients: a prospective randomized international phase II study (NAVoTrial 03)

2021 ◽  
Vol 13 ◽  
pp. 175883592110229
Author(s):  
Francesco Grossi ◽  
Piotr Jaśkiewicz ◽  
Marion Ferreira ◽  
Grzegorz Czyżewicz ◽  
Dariusz Kowalski ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Current Knowledge ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Comparable Efficacy ◽  
Open Label ◽  
Oral Vinorelbine ◽  
First Line Therapy ◽  
Nsclc Patients

Objective: The study investigated the efficacy and safety of oral vinorelbine-cisplatin (OV-CDDP) and gemcitabine-cisplatin (GEM-CDDP) in patients with squamous non-small cell lung cancer (sq-NSCLC). Patients and methods: This was an open-label, prospective, multicenter, international phase II study that enrolled untreated patients with advanced sq-NSCLC. Patients were randomized to receive 3-week cycles of either 60–80 mg/m2 OV days 1 and 8 in combination with 80 mg/m2 CDDP day 1 (arm A) or 1250 mg/m2 GEM days 1 and 8 in combination with 75 mg/m2 CDDP day 1 (arm B). After four cycles, patients without disease progression continued maintenance dose of OV or GEM until progression or unacceptable toxicity. The primary objective was disease control rate (DCR). Secondary objectives included progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), safety, and quality of life (QoL). Results: A total of 114 patients with sq-NSCLC were randomized, and 113 were treated (57 in arm A and 56 in arm B). DCR was high in both arms: 73.7% (95%CI: 62.4–100.0) in arm A and 75.0% (95%CI: 63.7–100.0) in arm B. Median PFS and TTF were similar in arm A and B 4.2 and 2.8 months, and 4.3 and 3.1 months, respectively. Even though the difference was not significant, the OS was 10.2 for arm A and 8.4 months for arm B. The safety profiles were consistent with the current knowledge of adverse events. QoL results revealed an improvement in patients under OV treatment. Conclusion: The OV-CDDP combination showed comparable efficacy to GEM-CDDP with acceptable safety profile and enhanced patients’ QoL. Trial registration: The study was registered under EudraCT number 2012-003531-40.

Preliminary results of a phase II study of alrizomadlin (APG-115), a novel, small-molecule MDM2 inhibitor, in combination with pembrolizumab in patients (pts) with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic (I-O) drugs.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2506-2506
Author(s):  
Anthony W. Tolcher ◽  
James Andrew Reeves ◽  
Meredith McKean ◽  
Bartosz Chmielowski ◽  
Joseph Thaddeus Beck ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Solid Tumors ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Nerve Sheath Tumor ◽  
Advanced Solid Tumors ◽  
Antitumor Effects ◽  
Ecog Performance Status ◽  
Multiple Tumor

2506 Background: Alrizomadlin (APG-115) restores TP53 function, activating p53-mediated apoptosis in tumor cells with wild-type TP53 and/or MDM2 amplification. Alrizomadlin also functions as a host immunomodulator and hence may restore antitumor activity in pts with cancers failing PD-1/PD-L1 blockade. Methods: This US multicenter trial assessed alrizomadlin combined with pembrolizumab in pts with unresectable/metastatic melanoma or advanced solid tumors that had failed I-O drugs; or pts with malignant peripheral nerve sheath tumor (MPNST), liposarcoma, or ATM mutant solid tumors that had failed any standard therapy. Eligible pts had ECOG performance status of 0-2 and no CNS metastases. The phase II study cohorts included pts with melanoma, NSCLC, solid tumor with ATM mutation, well-differentiated/dedifferentiated liposarcoma, urothelial carcinoma, and MPNST. Alrizomadlin was administered orally at 150 mg once every other day for 2 consecutive weeks with 1 week off and pembrolizumab at 200 mg via IV infusion for 30 minutes on Day 1 of a 21-day cycle. Results: As of December 25, 2020, 84 pts had been treated in 6 cohorts: melanoma (n = 26), NSCLC (n = 23), ATM mutation (n = 9), liposarcoma (n = 14), urothelial (n = 9), and MPNST (n = 3). In the PD-1/PD-L1 inhibitor-failed melanoma cohort, there was 1 confirmed partial response (PR) out of 5 pts with uveal melanoma, 2 PR (1 confirmed and 1 unconfirmed) of 5 pts with mucosal melanoma, and 1 confirmed PR of 11 pts with cutaneous melanoma. ORR in the melanoma cohort was 17.4% (4/23 evaluable pts), and the disease control rate was 60.9% (14/23). In the MPNST cohort, 1 of 3 pts had an unconfirmed ongoing PR. In I-O drug-failed NSCLC (n = 14 evaluable) and urothelial (n = 5 evaluable) cohorts, each reported 1 confirmed PR. Common treatment (alrizomadlin or pembrolizumab)-related adverse events (TRAEs) (≥ 10%) were nausea (63.1%), thrombocytopenia (36.9%), vomiting (33.3%), fatigue (31.0%), decreased appetite (27.4%), diarrhea (21.4%), neutropenia (15.4%), and anemia (11.9%). Grade ≥ 3 TRAEs (≥ 5%) included thrombocytopenia (20.2%), neutropenia (14.2%), and anemia (8.3%). Eleven pts discontinued treatment due to AEs: 5 were treatment related, including 2 grade 4 thrombocytopenia, and 1 each of grade 2 vomiting, grade 2 fatigue, and grade 2 posterior reversible encephalopathy syndrome (PRES). Three treatment-related SAEs were PRES, pyrexia, and asthenia. Conclusions: Alrizomadlin combined with pembrolizumab is well tolerated and may restore antitumor effects in pts with cancer resistant to or intolerant of I-O drugs, as suggested by preliminary antitumor activities in multiple tumor types. Internal study identifiers: APG-115-US-002; Keynote MK-3475-B66. Clinical trial information: NCT03611868.

Phase II Study of Uracil-Tegafur With Leucovorin in Elderly (≥ 75 years old) Patients With Colorectal Cancer: ECOG 1299

2007 ◽  
Vol 25 (34) ◽  
pp. 5397-5402 ◽  
Author(s):  
Howard S. Hochster ◽  
Weixiu Luo ◽  
Elizabeta C. Popa ◽  
Bruce T. Lyman ◽  
Mary Mulcahy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Elderly Patients ◽  
Survival Time ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Old Patients ◽  
Gi Toxicity ◽  
Grade 3

Purpose To evaluate the tolerability and effectiveness of uracil-tegafur (UFT) with leucovorin (LV) in the treatment of elderly patients with advanced colorectal cancer. Patients and Methods Patients ≥ 75 years of age with previously untreated colorectal cancer were eligible for this phase II, single-arm, open-label, multicenter cooperative group clinical trial. UFT 100 mg/m2 plus LV 30 mg orally every 8 hours for 28 days every 35 days was administered until progression. Results Fifty-eight patients were enrolled between June 2000 and July 2001, and 55 were treated. The median age of treated patients was 81 years (range, 75 to 90 years), 26 patients were (47%) women, and 80% had good performance status (0 to 1). The observed overall response rate was 22% (95% CI, 11.8% to 35.0%). The estimated median overall survival time was 13.0 months (95% CI, 9.6 to 17.4 months), and median progression-free survival time was 4.6 months (95% CI, 2.6 to 6.7 months). Among the 56 treated patients (including one ineligible patient), 31 (55%) experienced grade 3 to 4 toxicities, most commonly diarrhea (25%) and GI toxicity (36%), with patients older than 85 years of age at highest risk. Conclusion The results of this trial support the efficacy of oral UFT/LV in elderly patients with colorectal cancer. The regimen is tolerated moderately well overall, particularly as compared with other fluoropyrimidine regimens, although there is increased GI toxicity in the most elderly. These results suggest that studies using newer oral fluoropyrimidine analogs should be investigated in this patient population.

scholarly journals Repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy (ePIPAC) with oxaliplatin as a palliative monotherapy for isolated unresectable colorectal peritoneal metastases: protocol of a Dutch, multicentre, open-label, single-arm, phase II study (CRC-PIPAC)

BMJ Open ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. e030408 ◽  
Author(s):  
Koen P Rovers ◽  
Robin J Lurvink ◽  
Emma CE Wassenaar ◽  
Thomas JM Kootstra ◽  
Harm J Scholten ◽  
...  
Keyword(s):  
Phase Ii ◽  
Palliative Treatment ◽  
Phase Ii Study ◽  
Performance Status ◽  
Tumour Response ◽  
Competent Authority ◽  
Peritoneal Metastases ◽  
Open Label ◽  
Link Type ◽  
Number Of Patients

IntroductionRepetitive electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX) is offered as a palliative treatment option for patients with isolated unresectable colorectal peritoneal metastases (PM) in several centres worldwide. However, little is known about its feasibility, safety, tolerability, efficacy, costs and pharmacokinetics in this setting. This study aims to explore these parameters in patients with isolated unresectable colorectal PM who receive repetitive ePIPAC-OX as a palliative monotherapy.Methods and analysisThis multicentre, open-label, single-arm, phase II study is performed in two Dutch tertiary referral hospitals for the surgical treatment of colorectal PM. Eligible patients are adults who have histologically or cytologically proven isolated unresectable PM of a colorectal or appendiceal carcinoma, a good performance status, adequate organ functions and no symptoms of gastrointestinal obstruction. Instead of standard palliative treatment, enrolled patients receive laparoscopy-controlled ePIPAC-OX (92 mg/m2body surface area (BSA)) with intravenous leucovorin (20 mg/m2BSA) and bolus 5-fluorouracil (400 mg/m2BSA) every 6 weeks. Four weeks after each procedure, patients undergo clinical, radiological and biochemical evaluation. ePIPAC-OX is repeated until disease progression, after which standard palliative treatment is (re)considered. The primary outcome is the number of patients with major toxicity (grade ≥3 according to the Common Terminology Criteria for Adverse Events v4.0) up to 4 weeks after the last ePIPAC-OX. Secondary outcomes are the environmental safety of ePIPAC-OX, procedure-related characteristics, minor toxicity, postoperative complications, hospital stay, readmissions, quality of life, costs, pharmacokinetics of oxaliplatin, progression-free survival, overall survival, and the radiological, histopathological, cytological, biochemical and macroscopic tumour response.Ethics and disseminationThis study is approved by an ethics committee, the Dutch competent authority and the institutional review boards of both study centres. Results are intended for publication in peer-reviewed medical journals and for presentation to patients, healthcare professionals and other stakeholders.Trial registration numberNCT03246321, Pre-results;ISRCTN89947480, Pre-results; NTR6603, Pre-results; EudraCT: 2017-000927-29, Pre-results.

Sorafenib With Interferon Alfa-2b As First-Line Treatment of Advanced Renal Carcinoma: A Phase II Study of the Southwest Oncology Group

2007 ◽  
Vol 25 (22) ◽  
pp. 3296-3301 ◽  
Author(s):  
Christopher W. Ryan ◽  
Bryan H. Goldman ◽  
Primo N. Lara ◽  
Philip C. Mack ◽  
Tomasz M. Beer ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Renal Carcinoma ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Performance Status ◽  
Combined Treatment ◽  
Progression Free Survival ◽  
Interferon Alfa

Purpose This phase II study evaluated the activity of combined treatment with interferon alfa-2b and sorafenib, a Raf and multiple receptor tyrosine kinase inhibitor, in patients with advanced renal carcinoma. Patients and Methods Eligible patients had metastatic or unresectable renal carcinoma with a clear-cell component, no prior systemic therapy, performance status 0 to 1, and measurable disease. Treatment consisted of interferon alfa-2b 10 × 106 U subcutaneously three times weekly and sorafenib 400 mg orally bid. The primary end point was confirmed Response Evaluation Criteria in Solid Tumors response rate. Results Twelve (19%) of 62 assessable patients achieved an objective confirmed response. An additional 31 (50%) had an unconfirmed partial response or stable disease as best response. The median progression-free survival was 7 months (95% CI, 4 to 11 months). The most common adverse events were fatigue, anorexia, anemia, diarrhea, nausea, rigors/chills, leukopenia, fever, and transaminase elevation. Von Hippel-Lindau gene mutations were detected in four (22%) of 18 archival tumor specimens. Conclusion The confirmed response rate for the combination of sorafenib and interferon in advanced renal carcinoma is greater than expected with either interferon or sorafenib alone. The toxicity of this combination is dominated by adverse events common to interferon that limit further development of this regimen.

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