Tag Archives: Clinical Trial Results

Avastin/Tarceva Combination May Be No More Effective Than Avastin Monotherapy

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The purpose of this single arm, multicenter Phase II clinical trial was to assess the activity and tolerability of the combination of bevacizumab (Avastin®) and erlotinib (Tarceva®) in patients with recurrent ovarian, primary peritoneal or fallopian tube cancer. Eligible patients received two or fewer prior chemotherapy regimens for recurrent or refractory disease and no prior anti-VEGF or anti-EGFR drugs. Between July and October 2005, 13 patients were enrolled.

There were two major objective responses — one complete response of 16+ month duration and one partial response of 11 month duration, representing an overall response rate of 15%. Two patients had fatal gastrointestinal perforations, and therefore, the study was discontinued. The trial investigators concluded that there was no strong suggestion that the Avastin®/Tarceva® combination was superior to single agent Avastin®, and noted that the rate of gastrointestinal perforation was of concern. The investigators believe that identification of risk factors for gastrointestinal perforation will be important with respect to the use of Avastin in the treatment of ovarian cancer.

[Source: “Efficacy and safety of bevacizumab plus erlotinib for patients with recurrent ovarian, primary peritoneal, and fallopian tube cancer: A trial of the Chicago, PMH, and California Phase II consortia;” Nimeiri HS, et. al., Gynecol Oncol. 2008 Apr 17 (Epublication ahead of print).]

Epirubicin Improves Overall Survival Better Than Ifosfamide When Combined with Paclitaxel and Cisplatin

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Epirubicin (Ellence®) produced longer median overall survival (OS) than ifosfamide (Ifex®) in a recent phase II randomized clinical trial comparing (i) cisplatin, paclitaxel and ifosfamide, with (ii) cisplatin, paclitaxel and epirubicin, in newly diagnosed advanced epithelial ovarian cancer patients. In this trial, patients with histologically proven epithelial ovarian cancer were randomly assigned to receive first-line polychemotherapy with cisplatin/paclitaxel/epirubicin (CEP arm) or cisplatin/paclitaxel/ifosfamide (CIP arm) for six cycles every 21 days. Two hundred and eight patients were randomised between the two treatment arms. The Phase II clinical trial finds were as follows:

  • After a median follow-up of 82 months, median overall survival (OS) was 51 months in the CIP arm, and 65 months in the CEP arm; and
  • 5-year survival rates were 43% in the CIP arm, and 50% in the CEP arm.

The trial investigators note that the OS findings seem longer in duration than is commonly reported, especially considering that more than 50% of the newly diagnosed advanced ovarian cancer patients were suboptimally debulked or cytoreduced after their first surgery. The trial investigators concluded that this unexpected finding might be a consequence of the close surgical surveillance and aggressive chemotherapeutic approach.

[Source: “A phase II randomised clinical trial comparing cisplatin, paclitaxel and ifosfamide with cisplatin, paclitaxel and epirubicin in newly diagnosed advanced epithelial ovarian cancer: long-term survival analysis;” Fruscio R. et. al.; Br J Cancer. 2008 Feb 26;98(4):720-7.]

Comment: Although small in size, this Phase II randomized clinical trial suggests that aggressive surgical intervention followed by aggressive polychemotherapy (involving epirubicin or ifosfamide in tandem with paclitaxel and cisplatin) may increase overall survival in newly diagnosed, advanced-stage ovarian cancer survivors. The findings of at least one major clinical study cite that optimal cytoreduction, as a stand-alone independent factor, provides up to a 50% increase in actuarial survival. In the U.S., an “optimal” cytoreduction is generally defined as a surgical procedure that results in 1 centimeter or less of macroscopic cancer present within the body after surgery. The surprising results of the study discussed above seem to indicate that a suboptimal cytoreduction or debulking surgery followed by aggressive polychemotherapy may be beneficial in extending overall survival in newly diagnosed, advanced-stage ovarian cancer survivors. The issue of what measure should be used to define an “optimal” cytoreduction or debulking is not without controversy with the ovarian cancer arena.

NOV-002 and Carboplatin Slow Disease Progression of Platinum Drug Resistant Ovarian Cancer

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“Novelos Therapeutics, Inc. (OTCBB: NVLT), a biopharmaceutical company focused on the development of therapeutics to treat cancer and hepatitis, today announced continued encouraging results in an ongoing Massachusetts General Hospital Cancer Center and Dana-Farber/Harvard Cancer Center (DF/HCC) Phase 2 trial of NOV-002 in combination with carboplatin in platinum-resistant ovarian cancer patients. Fifteen patients have now been enrolled and, to date, 60% (9) have had slower than expected disease progression. NOV-002 was well-tolerated, further extending the excellent safety profile NOV-002 has demonstrated in previous studies. Detailed results of this trial will be presented as a poster at the 2008 annual meeting of the American Society of Clinical Oncology (ASCO) taking place May 30 – June 3 in Chicago, Illinois.

‘I am encouraged by these results in platinum-resistant ovarian cancer, with NOV-002 (in combination with carboplatin) apparently slowing disease progression in over half of the treated patients. Most women who have failed three lines of chemotherapy would be expected to progress in about eight weeks. I am excited to present the trial results at ASCO,’ said Dr. Carolyn Krasner, medical oncologist at the Massachusetts General Hospital Cancer Center and the Principal Investigator. ‘We look forward to working closely with Dr. Krasner, the Massachusetts General Hospital Cancer Center, Dana-Farber/Harvard and other institutions on designing and implementing a larger NOV-002 trial for this indication,’ said Harry Palmin, President and CEO of Novelos. ‘Our objective is to commence the next Phase 2 trial in platinum-resistant ovarian cancer in early 2009.’

According to the American Cancer Society, in 2007 approximately 22,000 U.S. women were diagnosed with ovarian cancer and 15,000 women were expected to die from it. There is a lack of effective treatment, particularly in the case of platinum-resistant patients. Once a woman’s ovarian cancer is defined as platinum-resistant the chance of having a partial or complete response to further platinum therapy is typically less than 10% and only 10-20% with other available agents. Thus, there is a major unmet medical need for this indication. …”

[Source: “Novelos Therapeutics Announces Continued Encouraging Results in Ongoing Phase 2 Ovarian Cancer Trial at Dan-Farber/Harvard Cancer Center;” Novelos Therapeutics, Inc. Press Release dated March 31, 2008.]

SNS-595 Shows Promise For Platinum-Resistant Ovarian Cancer Patients

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“Sunesis Pharmaceuticals, Inc. (Nasdaq: SNSS), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel small-molecule therapeutics, announced positive interim data from the company’s ongoing Phase 2 clinical trial of its lead product candidate, SNS-595, in platinum-resistant ovarian cancer patients.

In this Phase 2 clinical trial, single agent SNS-595 has demonstrated disease control (defined as stable disease, partial response or complete response) in 31 of 35 patients evaluable for best response using GOG-RECIST criteria. Of these 31 patients, one patient had a complete response, four patients had partial responses (two unconfirmed) and 26 patients had a best response of stable disease. All patients enrolled in the trial have previously failed treatment with platinum-containing regimens, and fourteen of the 35 patients have also failed prior treatment with doxorubicin HCl liposome injection (Doxil(R)). Both platinum-resistant and Doxil-resistant patients in the Phase 2 clinical trial have responded to SNS-595 therapy.

‘Recurrence rates among ovarian cancer patients remain high, and the majority of refractory patients are resistant to platinum-based therapies. Based on these interim data, SNS-595 appears to be a promising, active agent in a difficult-to-treat ovarian cancer patient population,’ said William P. McGuire, M.D., Medical Director of the Harry and Jeanette Weinberg Cancer Institute at Franklin, and a lead investigator for the Phase 2 trial.

Among forty-five patients with sufficient follow-up to yield safety data, SNS-595 was generally well tolerated at a dose level of 48mg/m2 administered once every three weeks. The most common adverse events reported thus far include nausea, fatigue, vomiting and alopecia. There was a low rate of febrile neutropenia or other Grade 3/4 adverse events, and manageable Grade 1/2 nausea or vomiting.

Based on the indications of clinical activity and the acceptable tolerability profile demonstrated to date among this patient population, the dose of SNS-595 in this trial has been increased to 60 mg/m2 over twenty-eight days. Patient accrual at this dose level is ongoing.

‘We are pleased by the strong signal of activity emerging from our Phase 2 clinical trial of SNS-595 at the 48mg/m2 dose level. Based on the drug’s observed safety profile and recommendations from advisors, we are exploring a higher dose of SNS-595 in this trial. Enrollment has begun at 60 mg/m2 and we expect to enroll approximately 30 patients at this dose by the third quarter of this year,’ said Daniel C. Adelman, M.D., Senior Vice President, Development and Chief Medical Officer of Sunesis. ‘Enthusiasm for SNS-595 among our clinical investigators is growing and enrollment in this trial has been accelerating. We expect to present further data from this Phase 2 clinical trial this year.’

The interim clinical results are being presented in a poster, “A Phase 2 Trial of SNS-595 in Women with Platinum-Refractory Epithelial Ovarian Cancer” (Abstract # 290), at the 39th Annual Meeting on Women’s Cancer hosted by the Society of Gynecologic Oncologists (SGO) in Tampa, Fla. through March 12, 2008.”

About SNS-595

SNS-595 is a novel naphthyridine analog, structurally related to quinolones, a class of compounds which has not been used previously for the treatment of cancer. SNS-595 is a specific DNA intercalator and topoisomerase II poison, causing replication-dependent site-selective double strand DNA damage, irreversible G2 arrest and rapid apoptosis. In non-clinical evaluations, SNS-595 demonstrates broad and potent activity in xenograft, syngeneic and drug-resistant models. In addition to the Phase 2 clinical trial in ovarian cancer patients, SNS-595 is currently being evaluated in combination with cytarabine in a Phase 1b acute leukemia clinical trial. In clinical trials conducted to date, SNS-595 has been generally well tolerated and has shown objective responses in both solid and hematologic tumor types.”

Quoted Source: [“Sunesis Pharmaceuticals Reports Positive Interim Data for SNS-595 Single-Agent Activity in Platinum-Resistant Ovarian Cancer”, MedicalNewsToday.com, March 11, 2008. (Emphasis added by posting author)].

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