Phase 2 trial of tisotumab vedotin in platinum-resistant ovarian cancer (innovaTV 208).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS5602-TPS5602 ◽  
Author(s):  
Haider Mahdi ◽  
Steven Robert Schuster ◽  
David M. O'Malley ◽  
Donna M. McNamara ◽  
Reshma A. Rangwala ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Primary Endpoint ◽  
Human Monoclonal Antibody ◽  
Single Agent ◽  
Ca 125 ◽  
Phase 2 ◽  
Phase 2 Trial ◽  
Platinum Resistant ◽  
Platinum Based Chemotherapy ◽  
Increased Risk

TPS5602 Background: Ovarian cancer (OC) is the most lethal gynecologic cancer, accounting for ≈185,000 deaths worldwide in 2018. Most patients (pts) initially respond to platinum-based chemotherapy (chemo), but more than 50% of pts recur. Pts who recur in ≤6 months have platinum-resistant OC (PROC), which is associated with poor prognosis. Standard therapy for PROC includes chemo ± bevacizumab (bev). However, many pts receive single-agent chemo, which demonstrates limited response and survival (≈12% ORR, 3-4 mo PFS, ≈12 mo OS). Therefore, there is an urgent need for novel therapeutic strategies. Tissue factor (TF) is a novel oncogenic target expressed in OC. Tisotumab vedotin (TV) is a first-in-class antibody drug conjugate comprising a TF-targeted fully human monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E. TV has shown encouraging antitumor activity and a manageable safety profile in PROC in the multicohort phase 1/2 innovaTV 201 study. innovaTV 208 is a multicenter, open-label, phase 2 trial with a safety run-in phase for a dose-dense regimen (DDR) evaluating the efficacy and safety of TV in pts with PROC. Methods: innovaTV 208 will enroll ≈142 adult pts with platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancer; measurable disease by RECIST v1.1; and ECOG score 0-1. Eligible pts must have received bev-containing treatment for OC. Pts with platinum-refractory disease, increased risk of bleeding, active ocular surface disease, or grade > 1 peripheral neuropathy will be excluded. A safety run-in phase for the DDR will be performed in up to 12 pts who received ≤5 prior treatment regimens for PROC. In the DDR, TV will be given at previously decided lower doses IV 3Q4W for the same dose intensity as the standard 1Q3W dose; the primary endpoint is incidence of DLTs. In phase 2, pts who received ≤1 prior cytotoxic chemo regimen for PROC will be randomized to receive TV administered as IV 1Q3W or as IV 3Q4W, if shown to be tolerable. The primary endpoint for phase 2 is confirmed ORR by RECIST v1.1. Secondary endpoints include DOR, time to response, DCR, CA-125 response rate by GCIG criteria, PFS, OS, pharmacokinetics, and safety. Clinical trial information: NCT03657043.

Phase 2 trial of single agent docetaxel in platinum and paclitaxel-refractory ovarian cancer, fallopian tube cancer, and primary carcinoma of the peritoneum

2003 ◽  
Vol 91 (3) ◽  
pp. 573-576 ◽  
Author(s):  
Maurie Markman ◽  
Kristine Zanotti ◽  
Kenneth Webster ◽  
Gertrude Peterson ◽  
Barbara Kulp ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fallopian Tube ◽  
Single Agent ◽  
Primary Carcinoma ◽  
Phase 2 ◽  
Fallopian Tube Cancer ◽  
Phase 2 Trial

Phase II study of gemcitabine and oxaliplatin in patients with recurrent ovarian cancer: an Australian and New Zealand Gynaecological Oncology Group study

2007 ◽  
Vol 17 (2) ◽  
pp. 359-366 ◽  
Author(s):  
P. Harnett ◽  
M. Buck ◽  
P. Beale ◽  
A. Goldrick ◽  
S. Allan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Single Agent ◽  
Recurrent Ovarian Cancer ◽  
Ca 125 ◽  
Platinum Sensitive ◽  
Best Response ◽  
Platinum Based Chemotherapy ◽  
Group A ◽  
Intent To Treat ◽  
Group B

Gemcitabine and oxaliplatin have shown single-agent activity in relapsed ovarian cancer. This combination was used to determine response rates, time-to-event efficacy measures, and toxicity in patients with recurrent ovarian cancer. Patients with prior platinum-based chemotherapy who had measurable lesions and/or elevated CA-125 levels were identified as group A (platinum-refractory/platinum-resistant patients) and group B (platinum-sensitive patients). All patients received gemcitabine 1000 mg/m2 on days 1 and 8 and oxaliplatin 130 mg/m2 on day 8 every 21 days for up to eight cycles. Seventy-five patients (21 in group A and 54 in group B), with a median age of 58 years (range, 37–78), were enrolled. A median of six cycles (range, 1–8) was administered. By intent-to-treat analysis, 15 patients with measurable disease achieved partial response for an overall best response rate of 20.0% (9.5% in group A and 24.1% in group B). CA-125 response was observed in 48.4% patients (30.0% in group A and 57.1% in group B). Median time to progressive disease was 7.1 months (95% CI, 5.6–9.0 months) with 5.0 months in group A and 8.3 months in group B. Median overall survival was 17.8 months (95% CI, 12.9–21.3 months) with 9.2 months for group A and 20.0 months for group B. Major grade 3/4 toxicities were neutropenia (61.3%), leukopenia (24.0%), nausea (16.0%), and vomiting (22.7%). We conclude that the combination of oxaliplatin and gemcitabine is active in patients with recurrent ovarian cancer, but the regimen is unsatisfactory for further study due to modest response and relatively high toxicity.

Panitumumab and pegylated liposomal doxorubicin in platinum-resistant epithelial ovarian cancer with KRAS wild-type: The PaLiDo study, a phase II nonrandomized multicenter study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5052-5052 ◽  
Author(s):  
Karina Dahl Steffensen ◽  
Marianne Waldstrøm ◽  
Niels Pallisgaard ◽  
Bente Lund ◽  
Kjell Bergfeldt ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Response Rate ◽  
Pegylated Liposomal Doxorubicin ◽  
Ca 125 ◽  
Wild Type ◽  
Platinum Resistant ◽  
Platinum Based Chemotherapy ◽  
Dermatologic Toxicity

5052 Background: Ovarian cancer (OC) patients with platinum-resistant recurrent disease have few therapeutic options and the response rates are only 10-20% using non-cross-resistant chemotherapeutic agents. The increasing number of negative trials for OC treatment has prompted an evaluation of new biologic agents, which in combination with chemotherapy may result in improvement in survival. Panitumumab is a fully human monoclonal antibody specific to the epidermal growth factor receptor (EGFR). No previous studies have evaluated the effect of panitumumab in OC based on KRAS mutation status. The main purpose was to investigate the response rate in platinum-resistant, KRAS wild-type OC patients treated with pegylated liposomal doxorubicin (PLD) supplemented with panitumumab. Methods: Major eligibility criteria were confirmed stage I-IV primary epithelial ovarian/fallopian/peritoneal cancer patients with progression either during or within 6 months after end of first or second line platinum-based chemotherapy. Only patients with measurable disease by CA125 criteria and with KRAS wild type were eligible. Patients were treated with panitumumab 6 mg/kg day 1 and day 15 and with PLD 40 mg/m² day 1, every 4 weeks. Tumor assessment was performed at baseline and at every third cycle according to CA-125 criteria. Results: A total of 46 patients were enrolled by 6 study sites in this multi-institutional phase II trial. Within the population evaluable for response (N=33), there was 8 CA125 responders for an overall response rate of 24.3 %. Progression-free and overall survival in the intention-to-treat population (N=43) was 2.7 months (2.5-3.2 months, 95%CI) and 8.1 months (5.6-11.7 months, 95%CI), respectively. The most common treatment related grade 3 toxicities included skin toxicity (42%), fatigue (19%) and vomiting (12%). Conclusions: The combination of PLD and panitumumab demonstrates efficacy in platinum refractory/resistant patients although the dermatologic toxicity was considerable.

scholarly journals Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial

The Lancet ◽  
2021 ◽  
Vol 397 (10271) ◽  
pp. 281-292 ◽  
Author(s):  
Stephanie Lheureux ◽  
Mihaela C Cristea ◽  
Jeffrey P Bruce ◽  
Swati Garg ◽  
Michael Cabanero ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Recurrent Ovarian Cancer ◽  
Phase 2 ◽  
Double Blind ◽  
Phase 2 Trial ◽  
Platinum Resistant ◽  
Platinum Refractory

A randomized phase II evaluation of weekly gemcitabine plus pazopanib versus weekly gemictabine alone in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5532-5532 ◽  
Author(s):  
Linda R. Duska ◽  
Jubilee Brown ◽  
Danijela Jelovac ◽  
Kathleen N. Moore ◽  
William P. McGuire ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tyrosine Kinases ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Open Label ◽  
Phase 2 Trial ◽  
Platinum Resistant ◽  
Valuable Treatment ◽  
Inhibition Of Angiogenesis ◽  
To Receive

5532 Background: Inhibition of angiogenesis is a valuable treatment strategy for ovarian cancer. Pazopanib (paz) is a potent angiogenic small molecular inhibitor of the tyrosine kinases VEGRF-1, -2, -3, PDGFR, c-kit and has shown activity as a single agent in ovarian cancer. We designed a trial to assess the benefit of adding paz to gemcitabine (gem) in patients with recurrent, advanced ovarian cancer. Methods: An open-label, randomized, multi-site, phase 2 trial was conducted (NCT01610206) including patients with platinum resistant or sensitive ovarian cancer with up to 3 prior lines of chemotherapy, and measurable or evaluable disease. Patients were randomly assigned (1:1) to receive weekly gem 1000 mg/m2 with or without paz 800 mg QD and stratified according to platinum sensitivity and number of prior lines (1 vs 2 or 3). The primary endpoint was PFS. Intent-to-treat was defined as all eligible patients who receive any protocol treatment with analysis based on randomized arm. Results: As of 3/2017, we randomized 148 and treated 146 patients (target sample size 148 eligible patients who receive any protocol treatment). 75 (46 platinum resistant, 61%) were randomly assigned to receive gem/paz and 71 (41 platinum resistant, 58%) to receive gem only. 110 patients (75%) had received 2 or 3 prior lines. There were no unexpected toxicities or deaths. Adverse events were more common in the gem/paz group. The most common grade 3–4 AEs (gem/paz vs gem) were: neutropenia (25 [33%] vs 15 [21%]), fatigue (7 [10%] vs 1 [2%]), hypertension (11 [15%] vs 1 [1%]), elevated alanine aminotransferase (8 [11%] vs 0), thrombocytopenia (9 [12%] vs 12[3%]) and anemia (7 [9%] vs 2 [3%]). There were 2 GI perforations in the paz arm. Median time on therapy was 12 weeks (range 1-55 weeks). Of the 138 patients off study to date, 30 (22%) were for AE’s (23 on gem/paz arm). Conclusions: The gem/paz combination is tolerable in this population, with patients tolerating multiple cycles with manageable toxicity. Median follow-up and PFS data will be presented after 122 events (progression or death) have occurred per protocol (currently 117 events). Clinical trial information: NCT01610206.

A phase III study comparing single-agent olaparib or the combination of cediranib and olaparib to standard platinum-based chemotherapy in recurrent platinum-sensitive ovarian cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6003-6003 ◽  
Author(s):  
Joyce F. Liu ◽  
Mark F. Brady ◽  
Ursula A. Matulonis ◽  
Austin Miller ◽  
Elise C. Kohn ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Primary Endpoint ◽  
Parp Inhibitor ◽  
Single Agent ◽  
Progression Free Survival ◽  
Phase Iii ◽  
High Grade ◽  
Primary Analysis ◽  
Open Label ◽  
Platinum Based Chemotherapy

6003 Background: Combination cediranib (C) and olaparib (O) improved progression-free survival (PFS) in patients (pts) with relapsed platinum (plat)-sensitive high-grade ovarian cancer (ovca) compared to O alone in a Phase 2 trial (NCT01116648). We conducted this randomized, open-label Phase 3 trial (NCT02446600) to assess whether combination C+O, or O alone, was superior to standard of care (SOC) plat-based therapy in relapsed plat-sensitive ovca. Methods: Eligible pts had recurrent plat-sensitive [ > 6-month plat-free interval (PFI)] high-grade serous or endometrioid, or BRCA-related, ovca. One prior non-plat therapy and unlimited prior plat-therapies were allowed; prior anti-angiogenics in the recurrent setting or prior PARP inhibitor were exclusions. Pts were randomized 1:1:1 to SOC (carboplatin/paclitaxel; carboplatin/gemcitabine; or carboplatin/liposomal doxorubicin), O (300mg twice daily), or C+O (C 30mg daily + O 200mg twice daily). Randomization was stratified by g BRCA status, PFI (6-12 vs > 12 months), and prior anti-angiogenic therapy. Target sample size was 549 pts; primary analysis occurred 2 years after the last pt enrolled. The primary endpoint was PFS. Type 1 error = 0.025 was controlled by a gatekeeping hierarchy that assessed C+O vs SOC, then O alone vs SOC, and finally C+O vs O. All maintenance therapy was prohibited. Results: Between 4FEB2016 and 13NOV2017, 565 pts enrolled (187 SOC, 189 O, 189 C+O), and 528 pts initiated treatment (166 SOC, 183 O, 179 C+O). 23.7% of patients had g BRCAmut. Median follow-up was 29.1 months. 53 pts on SOC initiated non-protocol therapy (predominantly PARP inhibitor maintenance) before disease progression. The hazard ratio (HR) for PFS was 0.856 (95% CI 0.66-1.11, p = 0.08, 1-tail) between C+O and SOC and 1.20 (95% CI 0.93-1.54) between O and SOC, with median PFS of 10.3, 8.2, and 10.4 months for SOC, O, and C+O, respectively. Response rates were 71.3% (SOC), 52.4% (O), and 69.4% (C+O). In gBRCA pts, HR for PFS was 0.55 (95% CI 0.73-1.30) for C+O vs SOC, and 0.63 (95% CI 0.37-1.07) for O vs SOC. In non-g BRCA pts, HR for these comparisons was 0.97 (95% CI 0.73-1.30) and 1.41 (1.07-1.86). No OS differences between arms were observed at 44% events. Pts receiving C+O (vs SOC) had more frequent Grade 3 or higher gastrointestinal (30.1% vs 8.4%), hypertension (31.7% vs 1.8%), and fatigue events (17.5% vs 1.8%). Conclusion: C+O demonstrated similar activity to SOC in relapsed plat-sensitive ovca but did not meet the primary endpoint of improved PFS. Clinical trial information: NCT02446600.

Phase 2 Trial of Moderately High Dose Single Agent Mitoxantrone in Platinum and Paclitaxel-Refractory Ovarian Cancer

1998 ◽  
Vol 70 (1) ◽  
pp. 123-126 ◽  
Author(s):  
Maurie Markman ◽  
Stuart M. Lichtman ◽  
Howard Homesley ◽  
Alexander Kennedy ◽  
Kenneth Webster ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Single Agent ◽  
High Dose ◽  
Phase 2 ◽  
Phase 2 Trial

Phase 2 trial of single-agent gemcitabine in platinum-paclitaxel refractory ovarian cancer

2003 ◽  
Vol 90 (3) ◽  
pp. 593-596 ◽  
Author(s):  
Maurie Markman ◽  
Kenneth Webster ◽  
Kristine Zanotti ◽  
Barbara Kulp ◽  
Gertrude Peterson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Single Agent ◽  
Phase 2 ◽  
Phase 2 Trial

Phase II study of MKC-1 in patients with metastatic or resistant epithelial ovarian cancer or advanced endometrial cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5577-5577 ◽  
Author(s):  
C. Elser ◽  
H. Hirte ◽  
L. Kaizer ◽  
H. Mackay ◽  
S. Bindra ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Endometrial Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Gastrointestinal Disorder ◽  
Ca 125 ◽  
Platinum Resistant ◽  
Parallel Group ◽  
Grade 3

5577 Background: MKC-1 is a novel oral cell cycle inhibitor with preclinical activity in xenograft models of human ovarian and endometrial cancers. MKC-1 also reduces pAKT, an attractive target in endometrial cancer due to frequent PTEN mutations. Methods: The objective of this phase II study is to assess the efficacy of MKC-1 in 2 patient (pt) populations: metastatic or recurrent platinum-resistant ovarian cancer (EOC) and advanced endometrial cancer (EC). Three prior lines of treatment were allowed in both groups. A two arm, parallel group multicenter 2-stage design was used. The primary endpoint was tumor response by RECIST or CA-125. MKC-1 125 mg/m2 was administered orally twice daily for 14 days in 28-day cycles. Results: Accrual to stage one is complete with 21 pts in each arm. 19 pts with EOC (median age 56 yrs, range 31–71) and 9 patients with EC (median 63 range 50–74) were available for efficacy. A total of 66 cycles (EOC/EC: 39/27cycles) median 2 per patient (range 1–8) were delivered. 11/4 pts had prior adjuvant CT, 14/10 had prior systemic CT for advanced disease, and 2/6 received prior radiation. In pts with EOC, 7 pts have stable disease (SD), 12 progressive disease (PD), 2 remain on study. Median time to progression is 1.8 months. In pts with EC 4 pts had SD, 5 PD, 6 remain on study. Toxicity data are available in 28 pts (17/11). Most common adverse events (AE) possibly related to MKC-1 were fatigue, nausea, elevated ALT or AST, urine discoloration, anemia, anorexia, elevated AP and gastrointestinal disorder in 55%, 39%, 36%, 24%, 23%, 21%, 21%, and 21 % of cycles respectively. The only possibly related grade 3+ AEs were neutropenia, leucopenia and hyponatremia in 9 %, 3 %, and 2% of cycles. Conclusions: MKC-1 was well tolerated in both patient populations. Single agent MKC-1 has insufficient activity in platinum resistant EOC to warrant further investigation. Updated clinical data for both patient groups will be presented at the meeting. [Table: see text]

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