Multicenter, Randomized Phase II Trial of Oral CI-1033 for Previously Treated Advanced Ovarian Cancer

2005 ◽  
Vol 23 (24) ◽  
pp. 5597-5604 ◽  
Author(s):  
Susana Campos ◽  
Oday Hamid ◽  
Michael V. Seiden ◽  
Amit Oza ◽  
Marie Plante ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adverse Events ◽  
Phase Ii ◽  
Survival Rates ◽  
Growth Factor Receptor ◽  
Advanced Ovarian Cancer ◽  
Recurrent Ovarian Cancer ◽  
Median Number ◽  
Open Label ◽  
Heavily Pretreated

Purpose To evaluate the antitumor activity and toxicity of two doses of CI-1033 in patients with platinum-refractory or recurrent ovarian cancer, and to determine baseline expression of epidermal growth factor receptor in tumor cells. Patients and Methods This phase II, open-label clinical trial evaluated CI-1033 in patients with ovarian cancer who failed prior platinum-based therapy. Two oral doses of CI-1033 were evaluated—a 50-mg and a 200-mg oral dose administered daily for 21 days in a 28-day cycle. Patients were evaluated for tumor response and toxicity; in addition, archival baseline tumor samples were analyzed by immunohistochemistry for erbB1 to erbB4 status. Results One hundred five eligible patients were treated. Baseline demographic characteristics were balanced in this heavily pretreated patient population. The median number of prior chemotherapy regimens received was four. The most commonly encountered drug-related adverse events for both dose arms were gastrointestinal (diarrhea, nausea, stomatitis) toxicity, asthenia, and rash. No responses were observed. Stable disease was confirmed in 34% and 26% of patients in the 200-mg and 50-mg arms, respectively, and 1-year survival rates were 38.5% and 37.7%, respectively. Baseline erbB3 and erbB4 revealed the highest frequencies of expression, while erbB2 was the lowest. Conclusion CI-1033 did not show activity in unscreened patients with advanced ovarian cancer. At 50 mg/d, CI-1033 had a more favorable adverse events profile than at 200 mg/d. erbB3 and erbB4 receptors showed the highest expression in tumor samples while erbB2 revealed the least. There appears to be no association between baseline erbB expression and disease stability.

Incorporation of Pazopanib in Maintenance Therapy of Ovarian Cancer

2014 ◽  
Vol 32 (30) ◽  
pp. 3374-3382 ◽  
Author(s):  
Andreas du Bois ◽  
Anne Floquet ◽  
Jae-Weon Kim ◽  
Joern Rau ◽  
Josep M. del Campo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Growth Factor Receptor ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Line Chemotherapy

PurposePazopanib is an oral, multikinase inhibitor of vascular endothelial growth factor receptor (VEGFR) -1/-2/-3, platelet-derived growth factor receptor (PDGFR) -α/-β, and c-Kit. Preclinical and clinical studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment. This study evaluated the role of pazopanib maintenance therapy in patients with ovarian cancer whose disease did not progress during first-line chemotherapy.Patients and MethodsNine hundred forty patients with histologically confirmed cancer of the ovary, fallopian tube, or peritoneum, International Federation Gynecology Obstetrics (FIGO) stages II-IV, no evidence of progression after primary therapy consisting of surgery and at least five cycles of platinum-taxane chemotherapy were randomized 1:1 to receive pazopanib 800 mg once per day or placebo for up to 24 months. The primary end point was progression-free survival by RECIST 1.0 assessed by the investigators.ResultsMaintenance pazopanib prolonged progression-free survival compared with placebo (hazard ratio [HR], 0.77; 95% CI, 0.64 to 0.91; P = .0021; median, 17.9 v 12.3 months, respectively). Interim survival analysis based on events in 35.6% of the population did not show any significant difference. Grade 3 or 4 adverse events of hypertension (30.8%), neutropenia (9.9%), liver-related toxicity (9.4%), diarrhea (8.2%), fatigue (2.7%), thrombocytopenia (2.5%), and palmar-plantar erythrodysesthesia (1.9%) were significantly higher in the pazopanib arm. Treatment discontinuation related to adverse events was higher among patients treated with pazopanib (33.3%) compared with placebo (5.6%).ConclusionPazopanib maintenance therapy provided a median improvement of 5.6 months (HR, 0.77) in progression-free survival in patients with advanced ovarian cancer who have not progressed after first-line chemotherapy. Overall survival data to this point did not suggest any benefit. Additional analysis should help to identify subgroups of patients in whom improved efficacy may balance toxicity (NCT00866697).

Phase II study on the combination carboplatin-celecoxib in heavily pre-treated recurrent ovarian carcinoma patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15009-15009
Author(s):  
F. Legge ◽  
V. Salutari ◽  
A. Paglia ◽  
A. Testa ◽  
D. Lorusso ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Recurrent Ovarian Cancer ◽  
Platinum Resistant ◽  
Response To Chemotherapy ◽  
Short Period ◽  
Heavily Pretreated ◽  
Cox 2

15009 Background: Cyclooxygenase-2 (COX-2) has been shown to be involved in several steps of ovarian onset and progression and its overepression is associated with a poor chance of response to chemotherapy and poor prognosis in ovarian cancer. Celecoxib, an orally active selective COX-2 inhibitor, has been tested for its ability to potentiate the activity of carboplatin in treatment of heavily pretreated recurrent ovarian cancer patients. Methods: A phase II study was planned, considering the regimen active if at least 12 responses were observed among the 43 enrolled patients. Celecoxib (400 mg/die), and carboplatin (5 AUC) q28 were administered, until progression or unacceptable toxicity. Response was assessed by RECIST and also by Rustin criteria. Results: 34 pts (median age: 60 yrs, range 28–74) and an ECOG performance status (0/1/2) of (21/12/1), were enrolled. 58.8% of patients were platinum resistant (progressing during or < 6 months from primary treatment). Median number of previous chemotherapy regimens was 3 (range 2–6). Currently 27 patients are evaluable for response. The overall response rate (CR and PR) was 25.9% (2 CR, 5 PR) with stabilization of disease in 8 patients (29.6%). Four responses occurred in platinum sensitive and 3 in platinum resistant group Median time to response was 11 weeks (range 9–19) and median duration of response was 23 weeks (range 12–39). According to Rustin criteria 10 patients out of 25 (40%) were considered responsive to treatment (return of CA125 levels to normal level or >50% reduction). Overall, 143 cycles were administered with a median value of 3 cycles (range = 1–10). Moderate/severe toxicities were as follows: G3 anemia occurred in 2.3% cycles, G3 neutropenia in 4.6% cycles, G3 thrombocytopenia in 1.5% cycles, G3/4 gastrointestinal toxicity occurred in 4.6% cycles. Cutaneous diffuse erithema was observed in 2 patients, in both cases recovered with a short period of antihistaminic treatment; 2 cases of hypertension were documented, G2 hypersensitivity reactions during carboplatin infusion were observed in 4 cases. Conclusions: Celecoxib combined with carboplatin is well tolerated and has promising activity as salvage treatment in heavily pretreated recurrent ovarian cancer patients. No significant financial relationships to disclose.

Nonpegylated liposome-encapsulated doxorubicin (NPLED) and cyclophosphamide in the treatment of platinum-resistant ovarian cancer: Final results of a phase II study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15544-e15544
Author(s):  
Daniela Sambataro ◽  
Melania Caruso ◽  
Concetta Di Blasi ◽  
Giuseppe Lavenia ◽  
Salvatore Asero ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Single Agent ◽  
Progression Free Survival ◽  
Median Number ◽  
Open Label ◽  
Open Label Study ◽  
Free Survival ◽  
Resistant Refractory ◽  
Platinum Resistant

e15544 Background: Platinum resistant-refractory ovarian cancer (PRROC) patients have a poor outcome; single-agent therapy is still the gold standard, with overall response rate lesser than 20% and progression-free-survival is not higher than 4 months. Methods: We tested safety and activity of a two-drugs-regimen containing NPLED and cyclophosphamide in a phase II open label study. From October 2007 to October 2011 thirty-two patients with platinum-resistant/refractory disease were enrolled. Enrolled patients were pretreated with a median number of 2 lines of chemotherapy, ranging from 1 to 5. NPLED and cyclophosphamide were administered at the dose of 60 mg. and 600 mg p.s.m. respectively. Results: Patients received a median number of three cycles of chemotherapy. A total of 145 cycles were administered: as G3 toxicities we registered emesis (6%), diaorrhea (3%), asthenia, and alopecia. No grade 4 adverse events occurred. Among the 30 patients evaluable for response we observed 5 (17%) partial responses and 10 (33%) stable diseases. The median progression-free-survival was 13 weeks and the median survival was 46 weeks. Conclusions: These results are similar to other data reported in literature. In conclusion we may affirm that the association of NPLED and cyclophosphamide is active and safe when administered in PRROC, but it don’t modify the prognosis of this subset of patients.

A multicenter open-label phase II study of the efficacy and safety of palbociclib a cyclin-dependent kinases 4 and 6 inhibitor in patients with recurrent ovarian cancer.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 5557-5557 ◽  
Author(s):  
Gottfried E. Konecny ◽  
Andrea Elisabeth Wahner Hendrickson ◽  
Aminah Jatoi ◽  
Jill K. Burton ◽  
Jill Paroly ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Recurrent Ovarian Cancer ◽  
Efficacy And Safety ◽  
Open Label ◽  
Cyclin Dependent Kinases ◽  
Open Label Phase

Phase II Study of Clofarabine in Pediatric Patients With Refractory or Relapsed Acute Lymphoblastic Leukemia

2006 ◽  
Vol 24 (12) ◽  
pp. 1917-1923 ◽  
Author(s):  
Sima Jeha ◽  
Paul S. Gaynon ◽  
Bassem I. Razzouk ◽  
Janet Franklin ◽  
Richard Kadota ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Phase Ii ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Single Agent ◽  
Median Number ◽  
Open Label ◽  
Hematopoietic Stem ◽  
Platelet Recovery ◽  
Heavily Pretreated

Purpose To evaluate the efficacy and safety of clofarabine, a novel deoxyadenosine analog, in pediatric patients with refractory or relapsed acute lymphoblastic leukemia (ALL). Patients and Methods In a phase II, open-label, multicenter study, 61 pediatric patients with refractory or relapsed ALL received clofarabine 52 mg/m2 intravenously over 2 hours daily for 5 days, every 2 to 6 weeks. The median age was 12 years (range, 1 to 20 years), and the median number of prior regimens was three (range, two to six regimens). Results The response rate was 30%, consisting of seven complete remissions (CR), five CRs without platelet recovery (CRp), and six partial remissions. Remissions were durable enough to allow patients to proceed to hematopoietic stem-cell transplantation (HSCT) after clofarabine. Median CR duration in patients who did not receive HSCT was 6 weeks, with four patients maintaining CR or CRp for 8 weeks or more (8+, 12, 37+, and 48 weeks) on clofarabine therapy alone. The most common adverse events of grade ≥ 3 were febrile neutropenia, anorexia, hypotension, and nausea. Conclusion Clofarabine is active as a single agent in pediatric patients with multiple relapsed or refractory ALL. The toxicity profile is as expected in this heavily pretreated patient population. Studies exploring rational combinations of clofarabine with other agents are ongoing in an effort to maximize clinical benefit.

Phase II Study of Carboplatin, Paclitaxel, and Bevacizumab With Maintenance Bevacizumab As First-Line Chemotherapy for Advanced Müllerian Tumors

2010 ◽  
Vol 28 (1) ◽  
pp. 154-159 ◽  
Author(s):  
Richard T. Penson ◽  
Don S. Dizon ◽  
Stephen A. Cannistra ◽  
Maria R. Roche ◽  
Carolyn N. Krasner ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Single Agent ◽  
Area Under The Curve ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Ca 125 ◽  
Open Label ◽  
Peritoneal Cancer ◽  
Open Label Phase

Purpose New strategies are needed to improve outcomes for patients with advanced ovarian cancer. Bevacizumab is a recombinant humanized monoclonal antibody that neutralizes vascular endothelial growth factor but is associated with GI perforations (GIPs) in patients with recurrent disease. Patients and Methods An open-label, phase II clinical trial was conducted in newly diagnosed patients with stage ≥ IC epithelial müllerian tumors. Patients received intravenous (IV) carboplatin (area under the curve = 5), paclitaxel (175 mg/m2 IV), and bevacizumab (15 mg/kg IV) for six to eight cycles on day 1 every 21 days. Bevacizumab was omitted in the first cycle and continued as a single agent for 1 year. Results Sixty-two women participated in this study. Fifty-one patients (82%) were optimally surgically cytoreduced before treatment. The median age was 58 years (range, 18 to 77 years). Forty-five women (73%) had ovarian cancer, 10 (16%) had peritoneal cancer, four (6%) had fallopian tube cancers, and three (5%) had uterine papillary serous tumors. The majority of patients (90%) had stage III or IV disease. A median of 17 maintenance cycles (range, 0 to 25+ cycles) of bevacizumab (556 cycles) were administered with mild toxicity. Treatment was associated with two pulmonary embolisms and two GIPs, all occurring during the chemotherapy phase of treatment (364 total cycles). No grade 4 toxicities were seen during maintenance bevacizumab treatment. Radiographic responses were documented in 21 (75%) of 28 women with measurable disease (11 complete responses and 10 partial responses), with CA-125 responses in 76% of patients (11 complete responses, 21%; and 35 partial responses, 55%). The progression-free survival rate at 36 months was 58%. Conclusion The regimen of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab is feasible, safe, and worthy of future study in advanced ovarian cancer.

A phase II trial of combination irinotecan and oral etoposide chemotherapy in recurrent ovarian cancer: A Tohoku Gynecologic Cancer Unit (TGCU) study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5558-5558
Author(s):  
S. Kumagai ◽  
T. Shoji ◽  
Y. Yokoyama ◽  
T. Takano ◽  
H. Mizunuma ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Treatment Options ◽  
Gynecologic Cancer ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Median Number ◽  
Oral Etoposide ◽  
Eligibility Criteria ◽  
Platinum Resistant

5558 Background: Various problems still exist in the management of recurrent ovarian cancer and there are limited treatment options especially for the platinum resistant patients (pts). We conducted a phase II study to evaluate the efficacy and safety of the combination irinotecan/oral etoposide chemotherapy. Methods: Eligibility criteria included recurrent ovarian cancer with measurable disease or positive CA125, preserved organ function, and aged 20–75. Treatment was conducted with irinotecan (60 mg/m2 iv, day 1, 15) and oral etoposide (50 mg/body day 1–21), q 28 days until disease progression or unacceptable toxicity. Primary endpoint was response rate (RR) and secondary endpoints included toxicity, progression-free survival (PFS), and overall survival (OS). Results: 38pts were enrolled on this study from May 2003 to April 2007, and all pts were eligible. Median age was 57 yrs (range 37–74). PS 0 in 24 pts, 1 in 10 pts, and 2 in 4 pts. Median number of previous regimen was 2 (range 1–4). Median treatment cycles were 6 (range 2–27). RR (CR+PR) was 18/38 (47.4%), and CR+PR+SD rate was 31/38 (81.6%). Grade 3/4 adverse effect included leukopenia (50.0%), neutropenia (52.6%), anemia (18.4%) and thrombocytopenia (2.6%), nausea/vomiting (7.9%) and diarrhea (2.6%). Treatment-related death was not observed. Median PFS was 7 months (range 1–33) and OS was 19 months (range 4–60). Among 20 pts with platinum resistant cases, RR was 6/20 (30.0%), CR+PR+SD rate was 14/20 (70.0%), median PFS was 6 months (range 1–33), and OS was 24 months (range 5–60). Conclusions: Combination irinotecan/oral etoposide chemotherapy can achieve a superior management for the recurrent ovarian cancer without declining QOL, and also has the possibility to be one of the most effective regimens as second-line chemotherapy. No significant financial relationships to disclose.

Efficacy and safety of olaparib monotherapy in a subgroup of patients with a germline BRCA1/2 mutation and advanced ovarian cancer from a Phase II open-label study.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 5529-5529 ◽  
Author(s):  
Susan M. Domchek ◽  
Ronnie Shapira-Frommer ◽  
Rita K. Schmutzler ◽  
M. William Audeh ◽  
Michael Friedlander ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Advanced Ovarian Cancer ◽  
Efficacy And Safety ◽  
Open Label ◽  
Open Label Study ◽  
Label Study

Phase II pharmacokinetics of oral SM-88 in heavily pretreated advanced pancreatic ductal adenocarcinoma (PC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 277-277
Author(s):  
Marcus Smith Noel ◽  
Martin Fernandez-Zapico ◽  
Gerald H. Sokol ◽  
Giuseppe Del Priore
Keyword(s):  
Single Dose ◽  
Adverse Events ◽  
Phase Ii ◽  
Dose Finding ◽  
Ductal Adenocarcinoma ◽  
Clinical Activity ◽  
Published Data ◽  
Open Label ◽  
Heavily Pretreated ◽  
Repurposed Drugs

277 Background: SM88 is an oral tyrosine isomer ( TI) and repurposed drugs (CYP3a4 inducer, mTOR inhibitor, oxidative stress catalyst). This regimen has reported no drug related grade 3, 4 or 5 adverse events (JCO 2013 31: e22095) and potential clinical activity in PC (JCO 2018 36: TPS 4156). PC patients have risk factors for malabsorption and a cachexia syndrome rendering some oral therapies potential unreliable. We present PK data from the completely enrolled first stage of an ongoing dose finding phase II in PC. Methods: Open label randomized TI (control – 230 mg bid vs. experimental - 430 mg bid) along with the lowest approved doses of the other agents. Samples were drawn from four patients at pre-dose and up to six h post dosing on cycle day one for two cycles after a single dose of all four components. Results: Mean age: 71.3 (59 – 80), BMI = 25.3 (21.9 – 28.8) and median three prior chemo lines, two post-pancreas surgery and one s/p RT. There was no evidence that the combination altered the expected PKs at C2. There were no serious drug related adverse events. Favorable RECIST, PERCIST or biomarker activity was documented at both TI dose levels. The PK results of the repurposed drugs were consistent with the published data for these agents, despite the combination use and lower than typical label doses; data will be provided. These results were consistent with previous animal and healthier patient PK of SM88. Conclusions: Single dose C1 and C2 TI PKs are consistent with preclinical predictions (ESMO 2016. Ann Oncol (2016) 27 (supp_6): 1605P) and those previously reported in a healthier population of cancer patients (JCO 2018 36: TPS 4156). Based on these results and PK ones from the repurposed drugs, additional data is being collected in order to define the ongoing phase II expansion cohort dose. SM-88 appears to have predictable PK even in heavily pretreated PC patient with prior radiotherapy and surgery. Clinical trial information: NCT03512756. [Table: see text]

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