Rexahn Pharmaceuticals Submits Archexin Phase II Protocol for Ovarian Cancer to FDA - News

Rexahn Pharmaceuticals Submits Archexin Phase II Protocol for Ovarian Cancer to FDA

May 08, 2012 08:03 AM Eastern Daylight Time 

ROCKVILLE, Md.--(EON: Enhanced Online News)--Rexahn Pharmaceuticals, Inc. (NYSE Amex: RNN), a clinical stage pharmaceutical company developing and commercializing potential best in class oncology and CNS therapeutics, today announced that it has submitted a Phase II protocol for the clinical study of Archexin^® as a treatment of ovarian cancer to the U.S. Food and Drug Administration (FDA).

“Treatment options are limited for patients who are stricken with ovarian cancer, therefore we look forward to investigating Archexin as a potential combination treatment for this disease.”

The Phase II study will assess the safety and efficacy of Archexin when used in combination with both carboplatin and paclitaxel as a second-line therapy in subjects who are platinum-sensitive following their first relapse. The study will be conducted at multiple centers in the United States, and subjects will be randomized to receive either carboplatin/paclitaxel or carboplatin/paclitaxel/Archexin. Various measures of clinical benefit will be assessed

phase 11/111 - Comparing Three Combination Chemotherapy Regimens in Treating Patients With Stage IIB, Stage IIC, Stage III, or Stage IV Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer - Full Text View - ClinicalTrials.gov

Comparing Three Combination Chemotherapy Regimens in Treating Patients With Stage IIB, Stage IIC, Stage III, or Stage IV Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer - Full Text View - ClinicalTrials.gov

Comparing Three Combination Chemotherapy Regimens in Treating Patients With Stage IIB, Stage IIC, Stage III, or Stage IV Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

This study is currently recruiting participants.

Verified March 2012 by NCIC Clinical Trials Group

First Received on October 9, 2009.   Last Updated on March 9, 2012   History of Changes

Sponsor:	NCIC Clinical Trials Group
Collaborators:	National Cancer Institute (NCI) Grupo Español de Investigación en Cáncer de Ovario Cancer Research UK Southwestern Oncology Group (SWOG)
Information provided by (Responsible Party):	NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:	NCT00993655

  Purpose

RATIONALE: Drugs used in chemotherapy, such as paclitaxel, carboplatin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving them in different ways may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating patients with ovarian epithelial cancer, primary peritoneal cancer, and fallopian tube cancer.

PURPOSE: This randomized phase II/III trial is comparing the side effects of three combination chemotherapy regimens and to see how well they work in treating patients with stage IIB, stage IIC, stage III, or stage IV ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer.

Condition	Intervention	Phase
Fallopian Tube Cancer Metastatic Cancer Ovarian Cancer Peritoneal Cavity Cancer	Drug: carboplatin Drug: cisplatin Drug: paclitaxel Procedure: quality-of-life assessment	Phase II Phase III

A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptomatic malignant ascites

A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptomatic malignant ascites

Objective 
The recombinant fusion protein, aflibercept binds and neutralizes vascular endothelial growth factor (VEGF) A, B and placental growth factor (PlGF). Aflibercept inhibits ascites formation and reduces tumor burden in an ovarian cancer model. This open-label, single-arm, multicenter phase II study assessed the efficacy and safety of aflibercept in patients with advanced chemo-resistant epithelial ovarian cancer and symptomatic malignant ascites.

Methods 
Patients who required ≥3 previous paracenteses at 1-4 paracenteses per month received intravenous aflibercept 4mg/kg every 2weeks. The primary endpoint was repeat paracentesis response rate (RPRR), with response defined as at least a two-fold increase in time to repeat paracentesis compared with the baseline interval.

Results 
Ten out of 16 enrolled patients achieved a response; the RPRR was 62.5% (95% CI 35.4%–84.8%). Aflibercept was considered effective based on a hypothesis that the RPRR was ≥60%. Median time to repeat paracentesis was 76.0 (95% CI 64.0–178.0) days, which was 4.5 times longer than the baseline interval (16.8days). Median progression-free survival was 59.5 (95% CI 41.0–83.0) days. Twelve patients experienced adverse events considered related to aflibercept treatment including hypertension (7 patients), headache, anorexia, and dysphonia (3 patients each). Two patients experienced Grade 3/4 treatment-related adverse events (Grade 3 hypertension and weight loss in one patient, Grade 3 intestinal perforation in one patient).

Conclusion 
Aflibercept 4mg/kg every 2weeks was effective at controlling malignant ascites, reducing the interval between repeat paracenteses. The safety profile was consistent with that reported for anti-VEGF agents.

Phase II trial of bryostatin-1 in combination with cisplatin in patients with recurrent or persistent epithelial ovarian cancer: a California cancer consortium study.

Phase II trial of bryostatin-1 in combination with cisplatin in patients with recurrent or persistent epithelial ovarian cancer: a California cancer consortium study.

Background
The California Cancer Consortium has performed a Phase II trial of infusional bryostatin, a protein kinase C inhibitor isolated from the marine invertebrate bryozoan, Bugula Neritina, a member of the phylum Ectoprocta, in combination with cisplatin, in patients (pts) with recurrent platinum-sensitive or resistant ovarian cancer (OC).

Methods
Pts received bryostatin 45 mcg/m(2) as a 72 h continuous infusion followed by cisplatin 50 mg/m(2). Cycles were repeated every 3 weeks. Dosages were chosen based on phase I data obtained by the CCC in a population of pts with mixed tumor types.

Results
Eight pts with recurrent or persistent epithelial OC received 23 cycles of treatment. All pts had received previous platinum-based chemotherapy; two pts had received one prior course, five had received two prior courses, and one had received three prior courses of chemotherapy. The median age was 64 (range 32-72), and Karnofsky performance status 90 (range 80-100). A median of 3 cycles of chemotherapy were delivered (range: 1-5). The median progression-free and overall survivals were 3 and 8.2 months respectively. Best responses included two partial responses (one in a platinum-resistant pt), three pts with stable disease, and three progressions. All pts experienced Grade 3 or 4 toxicities including severe myalgias/pain/fatigue/asthenia in six pts, and severe nausea/vomiting/constipation in two other pts. One pt experienced a seizure and liver function tests were elevated in one other.

Conclusions
A modest response rate is observed in pts with recurrent or persistent ovarian cancer treated with the combination of bryostatin and cisplatin. The toxicity profile, however, observed in this pt population (primarily severe myalgias), precludes tolerability and prevents this combination from further investigation at this dose and schedule. It is possible that platinum pre-exposure in OC patients exacerbates observed toxicity. Phase II dosages of investigational agents in OC pts that are determined by phase I trials in pts with other tumor types should be chosen cautiously.

abstract: Sorafenib as a third line therapy in patients with epithelial ovarian cancer or primary peritoneal cancer: A phase II study

CONCLUSION: Sorafenib fails to achieve sufficient objective response or sustained disease stabilization as third-line treatment for EOC.

press release/abstract: Marshall Edwards Announces Publication of Phase II Clinical Trial Results - Phenoxodiol phase 11 ovarian cancer trial results (32 pts)

SAN DIEGO, March 21, 2011 /PRNewswire/ -- Marshall Edwards, Inc.(Nasdaq: MSHL), an oncology company focused on the clinical development of novel therapeutics targeting cancer metabolism, announced today the publication of results from a Phase II clinical trial of intravenous Phenoxodiol in combination with cisplatin in women with platinum-resistant ovarian cancer. The publication is now available on the International Journal of Gynecological Cancer website and scheduled to print in the May issue of the journal......

abstract: Int J Gynecol Cancer. 2011 Mar 15. [Epub ahead of print]

Phase II Evaluation of Phenoxodiol in Combination With Cisplatin or Paclitaxel in Women With Platinum/Taxane-Refractory/Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancers.

abstract: A phase II study of two topotecan regimens evaluated in recurrent platinum-sensitive ovarian, fallopian tube or primary peritoneal cancer: (GOG 146Q)

Oncolytics Biotech(R) Inc. Announces Randomized Phase II Ovarian Cancer Study to be Conducted by the Gynecologic Oncology Group and Sponsored by the National Cancer Institute

Press Release: Sept. 2 /PRNewswire-FirstCall/ - Oncolytics Biotech Inc. ("Oncolytics") (TSX:ONC, NASDAQ: ONCY) announced today that the Gynecologic Oncology Group (GOG) intends to conduct a randomized Phase II trial of weekly paclitaxel versus weekly paclitaxel with REOLYSIN(R) in patients with persistent or recurrent, ovarian, fallopian tube or primary peritoneal cancer (GOG186H). The study has been approved and will be sponsored by the Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, U.S. National Cancer Institute (NCI), which is part of the National Institutes of Health, under its Clinical Trials Agreement with Oncolytics. Oncolytics will provide clinical supplies of REOLYSIN for this study.......Information on the study will be available at www.clinicaltrials.gov.

A phase II study of sunitinib in patients with recurrent epithelial ovarian and primary peritoneal carcinoma: an NCIC Clinical Trials Group Study

Results: Of 30 eligible patients, most had serous histology (67%), were platinum sensitive (73%) and had two prior chemotherapies (60%). One partial response (3.3%) and three CA125 responses (10%) were observed, all in platinum-sensitive patients using intermittent dosing. Sixteen (53%) had stable disease. Five had >30% decrease in measurable disease. Overall median progression-free survival was 4.1 months. Common adverse events included fatigue, gastrointestinal symptoms, hand–foot syndrome and hypertension. No gastrointestinal perforation occurred.

Conclusions: Single-agent sunitinib has modest activity in recurrent platinum-sensitive ovarian cancer, but only at the 50 mg intermittent dose schedule, suggesting that dose and schedule may be vital considerations in further evaluation of sunitinib in this cancer setting.

phase 11 - RO4929097 in Treating Patients With Recurrent and/or Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer - Full Text View - ClinicalTrials.gov (location: PMH Toronto)

This study is not yet open for participant recruitment.

Verified by National Cancer Institute (NCI), August 2010

Purpose

RATIONALE: RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying the side effects and how well RO4929097 works in treating patients with recurrent and/or metastatic epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.

Curis (financial news) - phase 11 advanced ovarian cancer results Aug 2010 (hedgehog pathway inhibitor)

CAMBRIDGE, Mass., Aug 03, 2010 (BUSINESS WIRE) -- Curis, Inc. /quotes/comstock/15*!cris/quotes/nls/cris (CRIS 1.75, -0.02, -1.13%) , a drug development company seeking to develop next generation targeted small molecule drug candidates for cancer treatment, today reported its financial results for the second quarter ended June 30, 2010.

"Although we were disappointed to announce during the second quarter of 2010 that the topline results from Genentech and Roche's Phase II clinical trial with the hedgehog pathway inhibitor GDC-0449 in metastatic colorectal cancer indicated that the trial did not meet its primary endpoint, we are encouraged that Genentech is testing GDC-0449 in two additional tumor types, which should provide more information on its potential in cancers where we believe the Hedgehog pathway acts via different mechanisms of action," said Dan Passeri, Curis' President and Chief Executive Officer. "We expect that results will be available from the Phase II advanced ovarian cancer trial in the very near term and that we will communicate the topline results within August...."cont'd

PharmaLive: Curis / GDC-0449 [phase 11 trial results to follow

Note:  excerpt - Avastin + chemo

"Genentech and Roche are also conducting a randomized double-blind placebo-controlled Phase II trial in advanced ovarian cancer in a maintenance setting, which is evaluating the ability of GDC-0449 to slow the time to recurrence of cancer in patients whose disease is in complete remission, by impeding the residual cancer cells' ability to grow. Roche has indicated that results from this study are expected during the second half of 2010."

ASCO - Endocyte Officials to Present Results from Four Clinical Trials at ASCO Annual Meeting - PRECEDENT = EC145/platinum resistant ovarian

"Interim results from the PRECEDENT study, a randomized phase II study of the combination of EC145 and Doxil for the treatment of patients with platinum-resistant ovarian cancer, will be provided during an oral presentation. EC145 is a folate-targeted conjugate of a very potent chemotherapy drug."

Maintenance immunotherapy in recurrent ovarian cancer: Long term follow-up of a phase II study

"Therapy consisted of low-dose subcutaneous IL-2 and oral RA, administered on intermittent schedules for up to 5 years."