OPTIMOX2, a large randomized phase II study of maintenance therapy or chemotherapy-free intervals (CFI) after FOLFOX in patients with metastatic colorectal cancer (MRC). A GERCOR study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3504-3504 ◽  
Author(s):  
F. Maindrault-Goebel ◽  
G. Lledo ◽  
B. Chibaudel ◽  
L. Mineur ◽  
T. Andre ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Phase Ii ◽  
Median Duration ◽  
Phase Ii Study ◽  
Phase Iii ◽  
Randomized Phase Ii ◽  
Phase Iii Study ◽  
Large Phase ◽  
Duration Of Disease

3504 Background: The OPTIMOX1 study (JCO 2006) has shown that the strategy of 6 cycles of FOLFOX7 followed by maintenance therapy and FOLFOX reintroduction was as active and better tolerated than FOLFOX4 until progression. The aim of the OPTIMOX2 study was to evaluate a complete stop of chemotherapy after 6 bimonthly cycles of FOLFOX. Methods: Initially planned as a phase III study, OPTIMOX2 was downgraded to a large phase II study since the availability of bevacizumab. Patients (pts) were randomized between an OPTIMOX1 arm: 6 cycles of FOLFOX7 followed by LV5FU until progression and reintroduction of FOLFOX7, and the OPTIMOX2 arm: 6 cycles of FOLFOX7, complete stop of chemotherapy and reintroduction of FOLFOX7 before the tumor progression reached the baseline measures. Results: 187/200 planned pts were included between Feb 2004 and Nov 2005. Response rates were (OPTIMOX1 arm/OPTIMOX2 arm): CR 2%/2%, PR 54%/51%, stable 24%/33%, progression 11%/7%, non assessable 9%/7%. Median PFS were (OPTIMOX1 arm/OPTIMOX2 arm) 36/28 weeks (p=.01), PFS in responders 41/30 weeks (p=.001), PFS in stable patients 34/26 weeks (p=.23). Median duration of disease control (DDC), addition of PFS of first FOLFOX7 administration plus PFS of FOLFOX reintroduction if no progression at first evaluation, was 41 weeks in the OPTIMOX1 arm and 36 in the OPTIMOX2 arm, p=.17. Median duration of chemotherapy-free interval in the OPTIMOX2 arm was 25 weeks (5.7 months). Conclusions: Maintenance LV5FU therapy prolongs PFS. The quality of life of almost 6 months CFI can balance a small advantage in DDC for maintenance therapy. Our next goal is to evaluate maintenance therapy with targeted agents alone. [Table: see text]

Final results of OPTIMOX2, a large randomized phase II study of maintenance therapy or chemotherapy-free intervals (CFI) after FOLFOX in patients with metastatic colorectal cancer (MRC): A GERCOR study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4013-4013 ◽  
Author(s):  
F. Maindrault-Goebel ◽  
G. Lledo ◽  
B. Chibaudel ◽  
L. Mineur ◽  
T. Andre ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Maintenance Therapy ◽  
Phase Ii ◽  
Median Duration ◽  
Median Overall Survival ◽  
Phase Ii Study ◽  
Free Interval ◽  
Randomized Phase Ii ◽  
Large Phase ◽  
Duration Of Disease

4013 Background: The OPTIMOX2 study was designed to evaluate a complete stop of chemotherapy after 6 bimonthly cycles of FOLFOX. Methods: OPTIMOX2 is a large phase II study performed before the availability of bevacizumab. Patients (pts) were randomized between an OPTIMOX1 arm: 6 cycles of FOLFOX7 followed by LV5FU2 until progression then reintroduction of FOLFOX7, and the OPTIMOX2 arm: 6 cycles of FOLFOX7, complete stop of chemotherapy and reintroduction of FOLFOX7 before the tumor progression reached the baseline measures. Results: 202 pts were included between Feb 2004 and Apr 2006. Response rates were (OPTIMOX1/OPTIMOX2): CR+PR 63%/61%. Median PFS were OPTIMOX1/OPTIMOX2) 8.3/6.7 months (p=.04). Median duration of disease control (DDC), addition of PFS of first FOLFOX7 administration plus PFS of FOLFOX reintroduction if no progression at first evaluation, was 10.8m in the OPTIMOX1 arm and 9.0m in the OPTIMOX2 arm, p=.32. Median duration of chemotherapy-free interval (CFI) in the OPTIMOX2 arm was 4.6 months. Patients with poor prognostic factors had a shorter CFI, p=.01. Median overall survival was 24.6m in the OPTIMOX1 arm and 18.9m in the OPTIMOX2 arm, p=.05. Median survivals (OPTIMOX1/OPTIMOX2) were not reached/28.7m in patients with good prognostic and 20.9/14.5m in patients with poor prognostic. Conclusions: Maintenance LV5FU therapy prolongs PFS and OS, especially in patients with poor prognosis. CFI can be recommended only in selected patients without adverse prognostic factors. Our next study, DREAM, is evaluating maintenance therapy with targeted agents alone. No significant financial relationships to disclose.

A Phase II Study of Combined Adriamycin, L-PAM, and Methotrexate with Citrovorum Factor Rescue in Advanced Ovarian Carcinomas

1977 ◽  
Vol 63 (5) ◽  
pp. 469-477
Author(s):  
Claes Tropé ◽  
Willy Mattsson ◽  
Birger Ästedt
Keyword(s):  
Quality Of Life ◽  
Phase Ii ◽  
Median Duration ◽  
Phase Ii Study ◽  
Malignant Tumors ◽  
Ovarian Carcinomas ◽  
Highly Effective

In a phase II study of combined adriamycin, L-PAM, and methotrexate with citrovorum factor rescue, 14 of 15 patients with primary advanced or recurrent ovarian malignant tumors obtained an objective remission. In remission, all patients improved their quality of life. So far the median duration of remission is 5+ months for the complete responders and 7 months for the partial responders. Myelosuppression of varying severity occurred in 93 % of the courses. The regimen proved highly effective, although toxic in some advanced patients.

Randomised phase II study evaluating weekly docetaxel in combination with cisplatin and 5FU or capecitabine in metastatic oesophago-gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4067-4067 ◽  
Author(s):  
N. Tebbutt ◽  
V. Gebski ◽  
A. Strickland ◽  
D. Gibbs ◽  
E. Walpole ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Haematological Toxicity ◽  
Phase Iii ◽  
Stage Design ◽  
Weekly Docetaxel ◽  
Phase Iii Study ◽  
Recent Phase ◽  
Combination Regimens

4067 Background: Docetaxel (T), cisplatin (C) and 5FU (F) are active agents in oesophago-gastric cancer. A recent phase III study using TCF achieved a survival advantage but was associated with high rates of haematological toxicity (30% incidence of febrile neutropenia/neutropenic infection) as well as non-haematological side effects (Moiseyenko et al, 2005 Pr ASCO abstr 4002). Weekly docetaxel is associated with a lower incidence of haematological toxicity. This randomised phase II study aimed to test weekly docetaxel based combination chemotherapy regimens with the aim of maintaining the activity of docetaxel based combination regimens but reducing toxicity. Methods: Eligibility included; histologically confirmed, metastatic oesophageal or gastric (OG) carcinoma, measurable disease, PS0–2, adequate organ function, no prior treatment, informed consent. Pts were randomised to receive weekly (w) T 30 mg/m2 d1, 8 C 60 mg/m2 d1 F 200 mg/m2/d continuously q 3w or wT 30 mg/m2 d1, d8 and capecitabine (×)1600 mg/m2/d d1–14 q3w. The primary endpoint is confirmed response rate (RR), with each arm analysed independently. Simon’s 2 stage design was used, with 5/21 responses required in the first stage to allow continuation to 48 pts per arm. Results: 79 pts enrolled to date. Protocol specified interim analysis of efficacy after 21 pts per arm and of toxicity after 25 pts per arm ( Table ). In the first 21 pts per arm; 12 responses (11 confirmed) in wTCF arm, 6 responses (5 confirmed) in wTX arm. Trial continues accrual to target of 48 pts per arm. Complete accrual expected by April 2006. Updated data will be presented at the meeting. Conclusions: wTCF and wTX have encouraging activity and and a more favourable toxicity profile than TCF administered 3-weekly. [Table: see text] [Table: see text]

Results of the X-PECT study: A phase III randomized double-blind, placebo-controlled study of perifosine plus capecitabine (P-CAP) versus placebo plus capecitabine (CAP) in patients (pts) with refractory metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. LBA3501-LBA3501 ◽  
Author(s):  
Johanna C. Bendell ◽  
Thomas J. Ervin ◽  
Neil N. Senzer ◽  
Donald A. Richards ◽  
Irfan Firdaus ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Phase Ii ◽  
Median Overall Survival ◽  
Phase Iii ◽  
Controlled Study ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Randomized Phase Ii ◽  
Phase Iii Study

LBA3501 Background: Perifosine (P) is an oral, synthetic alkylphospholipid that inhibits or modifies signal transduction pathways including AKT, NFkB and JNK. A randomized phase II study examined P-CAP vs. CAP in pts with 2nd or 3rd line mCRC. This study showed improvement in mTTP (HR 0.254 [0.117, 0.555]) and mOS (HR 0.370 [0.180,0.763]). Based on these results, a randomized phase III study of P-CAP vs. CAP with a primary endpoint of overall survival (OS) in pts with refractory mCRC was initiated. Methods: The study was a prospective, randomized, double-blind, placebo-controlled randomized phase III trial. Eligible pts had mCRC which was refractory to all standard therapies. Pts randomized 1:1 to Arm A = P-CAP (P 50 mg PO QD + CAP 1000 mg/m2PO BID d1-14) or Arm B = CAP (placebo + CAP 1000 mg/m2 PO BID d 1-14). Cycles were 21 days. Baseline tumor block collection and a biomarker cohort of pts with pre- and on-treatment tumor and blood samples were performed. Results: Between 3/31/10 and 8/12/11, 468 pts were randomized, 234 pts were in each arm. Baseline demographics were balanced between the arms: age < 65y (A: 65%, B: 58.5%), male (A: 57.7%, B: 53.0%), ECOG PS 0 (A: 39.7%, B: 39.7%), K-ras mutant (A: 50.4%, B: 51.3%), and median number of prior therapies (A: 4, B: 4). As of 3/19/12, median follow up was 6.6 months. Median overall survival: Arm A = 6.4 mo, Arm B = 6.8 mo, HR 1.111 [0.905,1.365], p = 0.315. Median overall survival for K-ras WT pts: Arm A = 6.6 mo, Arm B = 6.8 mo, HR 1.020 [0.763,1.365], p = 0.894; K-ras mutant pts: Arm A = 5.4 mo, Arm B = 6.9 mo HR 1.192 [0.890,1.596], p = 0.238. Conclusions: Despite promising randomized phase II data, this phase III study shows no benefit in overall survival adding perifosine to capecitabine in the refractory colorectal cancer setting. Response rate, progression free survival, and safety data will be presented. Biomarker analysis is pending to see if subgroups of patients may have potential benefit.

Randomized phase II study of gemcitabine monotherapy versus gemcitabine with an EPA-enriched oral supplement in advanced pancreatic cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15109-e15109 ◽  
Author(s):  
Makoto Ueno ◽  
Satoshi Kobayashi ◽  
Shinichi Ohkawa ◽  
Ryo Kameda ◽  
Tomoko Andou ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Advanced Pancreatic Cancer ◽  
Chemotherapeutic Agents ◽  
Phase Iii ◽  
Correct Selection ◽  
Selection Probability ◽  
Randomized Phase Ii ◽  
Oral Supplement

e15109 Background: Gemcitabine is one of the standard chemotherapeutic agents for pancreatic cancer. Pancreatic cancer is often associated with cachexia. It had been reported that eicosapentaenoic acid (EPA) reduces proinflammatory cytokines, leading to improvement of cachexia. This study aimed to evaluate the efficacy and safety of gemcitabine with an EPA-enriched oral supplement in patients with unresectable pancreatic cancer. Methods: This phase II study consisted of patients (pts) who were randomly categorized into Arm A (1000 mg/m2 gemcitabine was administered on days 1, 8, and 15, every 4 weeks while an EPA-enriched oral supplement (Prosure, EPA 1056mg per pack) was taken daily at the maximum of 2 packs) or Arm B (gemcitabine monotherapy) at a 2:1 ratio. The primary endpoint was the evaluation of the 1-year survival. The sample size of 66 pts was chosen based on the randomized phase II selection design by Simon et al. (1985). The design suggests a correct selection probability of 80% if 1-year survival probabilities are 35% and 25% for two treatment arms. Results: From May 2010 to Oct. 2011, randomized 66 pts were examined (Arm A: 43, B: 23). The 1-year survival probability of Arm A was 35% while Arm B was 19%. The median survival times were 8.2 and 9.7 months, respectively. The hazard ratio was 0.79 [95%CI 0.46-1.37]; (p=0.40). The toxicities were mild and insignificant in both arms. Grade 3/4 toxicities (A/B %) included: neutropenia, 20.9/13.0; leukocytopenia, 30.2/21.7; hemoglobin, 14.0/8.7; thrombocytopenia, 9.3/8.7; nausea, 11.6/0.0; and diarrhea, 0/4.3. Although survival curve did not show significant differences, delayed effect was observed in Arm A. According to subgroup analyses, more beneficial effects were observed in men and pancreatic body-tail patients who took a lot of supplements (Table). Conclusions: Gemcitabine with an EPA-enriched oral supplement in advanced pancreatic cancer may be effective, and further phase III trial is needed. Clinical trial information: UMIN000003658. [Table: see text]

SPIRITT (study 20060141): A randomized phase II study of FOLFIRI with either panitumumab (pmab) or bevacizumab (bev) as second-line treatment (tx) in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 454-454 ◽  
Author(s):  
J. Randolph Hecht ◽  
Allen Lee Cohn ◽  
Shaker R. Dakhil ◽  
Mansoor N. Saleh ◽  
Bilal Piperdi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Grade 5 ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
Previously Treated

454 Background: Pmab has demonstrated significant improvement in progression-free survival (PFS) in pts with WT KRAS mCRC as 2nd-line tx in a phase III trial comparing pmab + FOLFIRI vs FOLFIRI alone. Here, we describe the results of SPIRITT, a multicenter, randomized phase II study evaluating pmab + FOLFIRI and bev + FOLFIRI in pts with WT KRAS mCRC previously treated with a 1st-line bev + oxaliplatin (Ox)-based chemotherapy regimen. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg + FOLFIRI Q2W or to bev 5.0 or 10.0 mg/kg + FOLFIRI Q2W. Eligibility criteria included: WT KRAS mCRC, ECOG ≤ 1, no prior irinotecan or anti-EGFR tx, and tx failure of prior 1st-line bev + Ox-based therapy (≥ 4 cycles). The primary endpoint was PFS; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. No formal hypothesis was tested. Results: 182 pts with WT KRAS mCRC were randomized. All pts received tx. Efficacy results are shown (table). Worst grade of 3/4 adverse events (AE) occurred in 78% of pts in the pmab + FOLFIRI arm and 65% in the bev + FOLFIRI arm. Grade 5 AEs occurred in 7% of pts in the pmab + FOLFIRI arm and 7% in the bev + FOLFIRI arm. Tx discontinuation due to any AE was 29% in the pmab + FOLFIRI arm and 25% in the bev + FOLFIRI arm. Conclusions: In this estimation study of pts with WT KRAS mCRC that previously received bev + Ox-based tx, the PFS hazard ratio (HR) was 1.01 (95% CI: 0.68 - 1.50). The OS HR was 1.06 (95% CI: 0.75 - 1.49). The observed ORR was higher in the pmab + FOLFIRI arm. 54% of bev + FOLFIRI pts received subsequent anti-EGFR tx. The safety profile for both arms was similar to previously reported studies. Tx discontinuation rates due to AEs were similar between the arms. Clinical trial information: NCT00418938. [Table: see text]

A phase II study of ADI-PEG 20 in combination with gemcitabine and docetaxel for the treatment of soft tissue sarcoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS11079-TPS11079
Author(s):  
Brian Andrew Van Tine ◽  
Nam Bui ◽  
Bethany Prudner ◽  
John S. Bomalaski ◽  
Bor-Wen Wu ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Surface Expression ◽  
Arginine Deiminase ◽  
Randomized Phase Ii ◽  
Argininosuccinate Synthase ◽  
Metastatic Sarcoma

TPS11079 Background: The combination of gemcitabine (G) and docetaxel (D) is a standard second line therapy for soft tissue sarcoma (STS) with a modest response rate. Recent studies have looked to add agents to enhance response. We have shown that argininosuccinate synthase 1 (ASS1) expression is silenced in 88% of all sarcomas (n = 708) (Bean et al., 2016, Cell Death and Disease), and that this loss is associated with a reliance on extracellular sources of the amino acid arginine. The arginine depleting enzyme PEGylated arginine deiminase (ADI-PEG 20) depletes extracellular arginine. Preclinical studies have demonstrated that arginine starvation and D administration induce c-Myc-driven hENT1 surface expression overcoming intrinsic cell surface G transporter related resistance. To test this hypothesis, we opened this multi-institutional randomized phase II trial examining the safety and efficacy of ADI-PEG 20 with G + D in STS (NCT03449901) in July of 2018. Methods: Eligible patients are adults with metastatic or unresectable histologically or cytologically confirmed FNCLCC grade 2 or 3 STS that would be standardly treated with G and/or D. Patients are treated with ADI-PEG 20 at a dose of 36 mg/m2 via intramuscular injection on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. G will be given intravenously at a dose of 750 mg/m2 over 90 minutes on Days 1 and 8 and D will be given intravenously at a dose of 75 mg/m2 over 60 minutes on Day 8 of each cycle. The median PFS of metastatic sarcoma patients receiving the standard G + D treatment was estimated to be 6.2 months in a randomized phase II study (Maki et. al., 2007, JCO). With the addition of ADI-PEG 20, we target to improve the median PFS to 9 months, a 45.2% (2.8 months or 12 weeks) improvement in patients treated on G + D + ADI-PEG 20 against the null hypothesis median PFS of 6.2 months to achieve 80% power to detect the improvement in PFS at a 5% alpha level. Tumor specimens (pre- and post-ADI-PEG 20 during week -1) and blood are collected for correlative studies including metabolomics, pharmacodynamics, immunogenicity and ASS1 biomarkers. Quality of life will be measured using FACT-G7. Clinical trial information: NCT03449901.

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