Tag Archives: RECIST criteria

Access Pharma Commences European Phase II Study of ProLindac™ + Paclitaxel In Platinum-Sensitive Ovarian Cancer Patients

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Access Pharmaceuticals announces commencement of a Phase 2 combination trial for its second generation DACH-platinum cancer drug, ProLindac™ (formerly known as AP5346), in platinum-sensitive ovarian cancer patients. This trial is an open-label, Phase 2 study of ProLindac™ given intravenously with paclitaxel. The combination trial will be conducted in up to eight European participating centers.

Access Pharmaceuticals, Inc., a biopharmaceutical company leveraging its proprietary drug-delivery platforms to develop treatments in the areas of oncology, cancer supportive care and diabetes, announces commencement of a Phase 2 combination trial for its second generation DACH-platinum [the active part of the currently-marketed drug, oxaliplatin] cancer drug, ProLindac™ (formerly known as AP5346), in platinum-sensitive ovarian cancer patients. This trial is an open-label, Phase 2 study of ProLindac™ given intravenously with paclitaxel. The combination trial will be conducted in up to eight European participating centers.

“We are very pleased to be able to begin this trial, which will be the first of several ProLindac-based combination studies in a variety of indications,” said Prof. Esteban Cvitkovic, Vice Chairman Europe and Senior Director Clinical Oncology R&D, Access Pharmaceuticals, Inc. He continued, “The ambitious two-step design of the study will allow us to rapidly benchmark ProLindac/paclitaxel in a clinical setting where there is a clear need to establish an improved standard for long-term tumor responses. When treated using the current first-line combination of carboplatin/paclitaxel, more than half of patients with advanced ovarian cancer will relapse. There are very few second-line options. Approved agents for second-line and later therapy are currently focused primarily on the palliation of more resistant tumors. This lack of valid second-line options presents an opportunity to prove the role of ProLindac-based combinations in ovarian cancer.”

“After optimizing ProLindac’s scaled-up manufacturing process, we are pleased to be moving forward with its clinical development,” said Jeff Davis, President and CEO, Access Pharmaceuticals, Inc. He continued, “We think there is a significant clinical need and commercial opportunity for safer, more effective platinum drugs.”

Access Pharmaceuticals previously announced positive safety and efficacy results from its Phase 2 monotherapy clinical study of ProLindac™ in late-stage, heavily pretreated ovarian cancer patients. In this study, 66% of patients who received the highest dose achieved clinically meaningful disease stabilization according to RECIST [Response Evaluation Criteria in Solid Tumors] criteria, including sustained significant reductions in CA-125 (the established specific serum marker for ovarian cancer) observed in several patients. No patient in any dose group exhibited signs of acute neurotoxicity, which is a major adverse side-effect of the approved DACH platinum, Eloxatin®. ProLindac was very well tolerated, with only minor sporadic hematologic toxicity.

Access Pharmaceuticals is evaluating various indications where DACH platinum-based combinations have been proven active, such as hepatocarcinoma, biliary tree cancer and pancreatic cancer before deciding on an expanded Phase 2 program.

About ProLindac:

ProLindac™ is a novel DACH platinum prodrug that has completed a phase 2 monotherapy study in ovarian cancer patients. It is a polymer therapeutic that utilizes a safe, water-soluble nanoparticulate system to deliver DACH platinum to tumors, while reducing delivery to normal tissue, resulting in an increase in drug effectiveness and a significant decrease in toxic side-effects seen in the currently marketed DACH platinum, Eloxatin®.

For more information, please visit http://www.accesspharma.com/product-programs/prolindac/.

Source: Access Pharmaceuticals Commences ProLindac Phase 2 Combination Clinical Trial – Multicenter, Open-Label Trial to Target Platinum-Sensitive Ovarian-Cancer Patients, News Release, Access Pharmaceuticals, Inc., November 3, 2010.

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Æterna Zentaris’ LHRH-Receptor Targeted Therapy AEZS-108 Produces Positive Preliminary Results in Advanced Stage Ovarian Cancer

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Preliminary Phase II clinical study evaluation shows that primary efficacy endpoint has been met for patients with advanced-stage, platinum-resistant, taxane-pretreated ovarian cancer who were treated with the targeted therapy AEZS-108.

Æterna Zentaris Inc. , a global biopharmaceutical company focused on endocrine therapy and oncology, today announced positive efficacy data from a Phase II study with its targeted therapy AEZS-108 (formerly AN-152 or ZEN-008), in patients with platinum–resistant, taxane-pretreated ovarian cancer. In a personalized healthcare approach, the study selected patients with tumors expressing luteinizing hormone-releasing hormone (LHRH) receptors, the key element in the targeting mechanism of AEZS-108. Under coordination by Prof. Günter Emons, MD, Chairman of the Department of Obstetrics & Gynaecology at the University of Göttingen, Germany, this open-label, multi-center and multi-national Phase II study (AGO-GYN 5) is being conducted by the German AGO Study Group (Arbeitsgemeinschaft Gynäkologische Onkologie / Gynaecological Oncology Working Group; www.ago-ovar.de), in cooperation with clinical sites in Europe.

Preliminary Phase II Clinical Study Results

Juergen Engel, Ph.D., President & CEO, AEterna Zentaris

Juergen Engel, Ph.D., President & Chief Executive Officer, Æterna Zentaris Inc. (Photo: AEterna Zentaris Inc.)

All 43 patients with LHRH-receptor positive ovarian cancer who entered study AGO-GYN 5 have completed their study treatment. A preliminary evaluation shows that the study met its primary efficacy endpoint of 5 or more responders in 41 evaluable patients.

Responders, as well as patients with stable disease after completion of treatment with AEZS 108, will now be followed to assess the duration of progression-free survival and, ultimately, overall survival. More detailed analyses, which will also include efficacy data from post-treatment follow-up of the ovarian cancer patients, are currently in preparation and will be presented at forthcoming scientific conferences.

Juergen Engel, Ph.D., Æterna Zentaris President and Chief Executive Officer stated, “We are pleased with the progress of this project. The successful completion of the recruitment and treatment phase and the apparent activity in this difficult group of cancer patients is encouraging. This is the basis we were looking for, in order to take the next steps in the further development of AEZS 108 in gynecological cancers and possibly also in prostate cancer.”

About the AEZS-108 Phase II Clinical Study

AEZS-108 represents a new targeting concept in oncology using a cytotoxic peptide conjugate which is a hybrid molecule composed of a synthetic peptide carrier and a well-known cytotoxic agent, doxorubicin. The design of this product allows for the specific binding and selective uptake of the cytotoxic conjugate by LHRH-receptor-positive tumors. The binding of AEZS-108 to cancerous cells that express these receptors results in its accumulation and preferential uptake in the malignant tissue.

In a Phase II study program entitled, “The antitumoral activity and safety of AEZS 108 (AN 152), a LHRH agonist linked doxorubicin in women with LHRH-receptor positive gynecological tumors“, patients with tumors expressing LHRH receptors are administered an intravenous infusion of 267 mg/m2 of AEZS 108 over a period of 2 hours, every Day 1 of a 21-day (3-week) cycle. The proposed duration of the study treatment is 6, 3-week cycles. Study AGO GYN 5 is performed with 14 centers of the German Gynecological Oncology Working Group (AGO; www.ago-ovar.de), in cooperation with 3 clinical sites in Europe.

The program was designed to include up to 82 patients; approximately 41 with a diagnosis of platinum-resistant, taxane-pretreated ovarian cancer, and 41 with disseminated endometrial cancer. For both indications, patient recruitment was planned in 2 stages with 21 and 20 patients, respectively, and the primary efficacy endpoint at the end of stage 2 was defined as 5 or more patients with partial or complete tumor responses according to Response Evaluation Criteria in Solid Tumors (RECIST) and/or Gynecologic Cancer Intergroup (GCIG) guidelines. Secondary endpoints include time to progression, survival, toxicity, as well as adverse effects.

Prior Phase I Clinical Trial Results

On June 3, 2007 positive results of an open, multi-center, sequential group, dose-escalation Phase I study in various gynecological cancers were presented at the American Society of Clinical Oncology’s (ASCO) Annual Meeting in Chicago, Illinois. Seventeen (17) patients with LHRH-receptor positive gynecological cancers were recruited. AEZS-108 was administered by intravenous infusion over two hours at dosages of 10, 20, 40, 80,160 and 267 mg/m2. At 160 mg/m2, six patients had a total of 32 cycles and at 267 mg/m2, seven patients had a total of 27 cycles. Most of the patients had been pretreated with various chemotherapies.

The study showed that AEZS-108 was well tolerated by patients with gynecological tumors. Furthermore, AEZS-108 is the first drug in a clinical study that targets the cytotoxic activity of doxorubicin specifically to LHRH-receptor expressing tumors. Finally, signs of anti-tumor activity were observed in seven out of 13 patients treated with 160 or 267 mg/m2 of AEZS 108, including three patients with complete or partial response

About AEZS-108

AEZS-108 Mechanism of Action

AEZS-108 Mechanism of Action (Photo: AEterna Zentaris Inc.)

AEZS-108 is a targeted cytotoxic peptide conjugate which is a hybrid molecule composed of a synthetic peptide carrier and a well-known cytotoxic agent, doxorubicin. The design of this product allows for the specific binding and selective uptake of the cytotoxic conjugate by LHRH-receptor-positive tumors. The binding of AEZS-108 to cancerous cells that express these receptors results in its accumulation in the malignant tissue. This binding is followed by internalization and retention of the cytotoxic drug, doxorubicin, in the cells. Therefore, since they target specific cells, cytotoxic conjugates are postulated to be less toxic, have less side-effects and are more effective in vivo than the respective non-conjugated/non-linked cytotoxic agents in inhibiting tumor growth.

About Ovarian and Endometrial Cancer

Ovarian cancer is one of the most common gynecologic malignancies and the fifth most frequent cause of cancer death in women, with most of the cases occurring in women between 50 and 75 years of age. Overall, ovarian cancer accounts for 4% of all cancer diagnoses in women and 5% of all cancer deaths. Approximately 26,000 new cases and 17,000 deaths from this disease are estimated in the European community every year (Source: Gynecologic Oncology, Volume 92, Issue 3, March 2004, Pages 819-826).

Cancer of the endometrium is the most common gynecologic malignancy and accounts for 6% of all cancers in women. The majority of the cases occur in postmenopausal women, with the largest number of women developing their cancers during their sixth decade. Approximately 38,000 new cases and 9,000 deaths from this disease are estimated annually in Europe (Source: Annals of Oncology 15:1149-1150, 2004).

About Æterna Zentaris Inc.

Æterna Zentaris Inc. is a global biopharmaceutical company focused on endocrine therapy and oncology, with proven expertise in drug discovery, development and commercialization. News releases and additional information are available at www.aezsinc.com.

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Small Phase II Study Tests the Use of Fulvestrant in the Treatment of Recurrent Epithelial Ovarian Cancer

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… University of Minnesota researchers evaluated the use of fulvestrant [Faslodex®] in women with recurrent ovarian or primary peritoneal cancer. …Using modified-RECIST criteria 13 patients (50%) achieved SD …[T]he University of Minnesota researchers concluded that fulvestrant is well-tolerated and efficacious. The researchers also noted that objective response rates are low, but disease stabilization was common.

It is well-known that the goal of treating recurrent ovarian cancer is disease control while minimizing toxicity. Previously, Fulvestrant (Faslodex®), a novel estrogen receptor (ER) antagonist, was proven clinically beneficial and well-tolerated in treating recurrent breast cancer. If a pathologist determines that a women’s ovarian cancer biopsy is estrogen receptor positive (ER+), there is a possibility that she may respond to anti-estrogen therapy.

On this basis, University of Minnesota researchers evaluated the use of fulvestrant in women with recurrent ovarian or primary peritoneal cancer. Patients with ER+, multiply recurrent ovarian or primary peritoneal carcinoma were eligible for trial enrollment if (i) they had measurable disease according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria, or (ii) an abnormal and rising CA-125 blood test measurement. Treatment consisted of single agent fulvestrant, 500 mg IM (intramuscular) on Day 1, 250 mg IM on Day 15, and 250 mg IM on Day 29 and every 28 days thereafter until the patient experienced intolerance or disease progression. Disease response was assessed by monthly physical exams and CA-125 levels as well as bimonthly CT scans. The clinical trial primary endpoint was “clinical benefit” (CB) (i.e., CB=complete response (CR) + partial response (PR) + stable disease (SD)) at 90 days).

Pursuant to the phase II fulvestrant clinical trial, the study researchers reported the following:

  • Thirty-one women were enrolled and 26 women (median age of 61) met inclusion criteria and received at least one dose;
  • Patients received a median of 5 prior chemotherapeutic regimens (range: 2-13) prior to enrollment;
  • One patient experienced CR (4%), one patient experienced PR (4%), and 9 patients experienced SD (35%) using modified-Rustin criteria (CA-125 level);
  • Using modified-RECIST criteria 13 patients (50%) achieved SD;
  • The median time to disease progression was 62 days (mean 86 days); and
  • Grade 1 toxicity included headache (1 patient) and bromidrosis (2 patients).

Based upon the foregoing results, the University of Minnesota researchers concluded that fulvestrant is well-tolerated and efficacious. The researchers also noted that objective response rates are low, but disease stabilization was common.

Primary Source:  A phase II study of fulvestrant in the treatment of multiply-recurrent epithelial ovarian cancer; Argenta PA, Thomas SG, Judson PL et. al., Gynecol Oncol. 2009 Feb 22. [Epub ahead of print]

M.D. Anderson Researchers Find GM-CSF and rIFN-gamma1b Plus Carboplatin Effective For the Treatment of Recurrent, Platinum-Sensitive Ovarian Cancer

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Researchers working in the Gynecologic Oncology Department of The University of Texas M.D. Anderson Cancer Center, reported Phase II clinical study results from their evaluation of the use of carboplatin, granulocyte-macrophage colony-stimulating factor (GM-CSF) and recombinant interferon gamma 1b (rIFN-gamma1b) in women with recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer. …

Researchers working in the Gynecologic Oncology Department of The University of Texas M.D. Anderson Cancer Center, reported Phase II clinical study results from their evaluation of the use of carboplatin, granulocyte-macrophage colony-stimulating factor (GM-CSF) and recombinant interferon gamma 1b (rIFN-gamma1b) in women with recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer.

As part of this Phase II clinical study, patients with recurrent, platinum-sensitive ovarian, fallopian tube or primary peritoneal cancer were treated with subcutaneous GM-CSF and rIFN-gamma1b before and after intravenous carboplatin until their disease progressed or unacceptable toxicity occurred. All patients had measurable disease and a chemotherapy-free interval >6 months. Response was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria and CA 125 blood serum levels. Between 2003 and 2007, 59 patients received a median of 6 cycles of therapy (range, 1 to 13 cycles). The median patient age at enrollment was 61 years (range, 35 to 79 years). The median patient time to disease progression prior to clinical study enrollment was 11 months (range, 6 to 58 months).

The M.D. Anderson researchers reported the following results:

Based upon the foregoing results, the researchers concluded that the pre- and post-carboplatin cytokine regimen resulted in a reasonable response and a hematologic profile that could invite further evaluation of its components in the treatment of patients with ovarian cancer.

Primary Source:  A phase II study of GM-CSF and rIFN-gamma1b plus carboplatin for the treatment of recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer; Schmeler KM, Vadhan-Raj S, Ramirez PT et. al., Gynecol Oncol. 2009 Mar 3. [Epub ahead of print].