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Clinical Trials Monthly - January 2012

Dear Colleague,

Each month Clinical Trials Monthly presents new and important trials that may benefit your patients. This month we’ve included trials for Fanconi anemia, breast cancer, Hodgkin and non-Hodgkin lymphoma, melanoma, and renal cell carcinoma. Each study summary has a link to the specific details about the trial in our online Clinical Trials Database. The complete list of all trials recruiting participants at Seattle Cancer Care Alliance can be found at www.seattlecca.org/clinicaltrials.

This Month’s Featured Clinical Studies
Breast Cancer Studies:

  • Combined targeted therapies for triple negative advanced breast cancer
  • Sunitinib in combination with paclitaxel, followed by doxorubicin, cyclophosphamide and G-CSF for locally
  • advanced or inflammatory breast cancer 
  • Zoledronic acid for breast cancer bone metastases
  • MARIANNE Trial: first-line trastuzumab-emtansine with pertuzumab vs. trastuzumab with taxane for HER2-positive progressive or recurrent locally advanced or metastatic breast cancer
  • Fanconi Anemia

Fanconi Anemia

  • Gene transfer for patients with Fanconi Anemia complementation group A (FANCA)

Melanoma

  • Melanoma Study: Vemurafenib for BRAF V600+ metastatic melanoma patients with brain metastases

Hodgkin’s and Non-Hodgkin’s Lymphoma

  • Hodgkin's Lymphoma Study: CAL-101 in relapsed/refractory disease
  • Non-Hodgkin's Lymphoma Study: CAL-101 in disease refractory to rituximab and alkylating agents

Renal Cell Carcinoma

  • Renal Cell Carcinoma Study: BNC105P with or after everolimus for progressive metastatic disease post tyrosine kinase inhibitors

Breast Cancer

Combined Targeted Therapies for Triple Negative, Advanced Breast Cancer—a Phase II Trial of Weekly Nab-Paclitaxel (Abraxane) and Bevacizumab (Avastin) Followed by Maintenance Targeted Therapy with Bevacizumab and Erlotinib (Tarceva) (NCT00733408)

Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, often work to stop the growth of tumor cells by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in various ways. Some block the tumor cells’ ability to grow and spread while others find tumor cells and help kill them or carry tumor-killing substances to them. Erlotinib may stop the growth of tumor cells by blocking enzymes needed for cell growth. Giving paclitaxel albumin-stabilized nanoparticle formulation together with bevacizumab and erlotinib may kill more tumor cells.
This Phase II trial studies how well paclitaxel albumin-stabilized nanoparticle formulation and bevacizumab work when followed by bevacizumab and erlotinib in treating patients with metastatic breast cancer. Enrolled patients receive the paclitaxel formulation IV once weekly for 24 weeks and bevacizumab IV once every two weeks for 24 weeks. Patients responding to this induction therapy receive bevacizumab IV once every two weeks plus oral erlotinib once daily.

Investigator: Jennifer Specht, MD

Phase II Study Evaluating the Safety and Efficacy of Sunitinib Maleate (Sutent®) in Combination with Weekly Paclitaxel (Taxol) Followed by Doxorubicin (Adriamycin) and Daily Oral Cyclophosphamide (Cytoxan) Plus G-CSF as Neoadjuvant Chemotherapy for Locally Advanced or Inflammatory Breast Cancer (NCT00513695)

The purpose of this study is to determine the safety and effectiveness of an investigational drug treatment for patients with locally advanced or inflammatory breast cancer. The investigational drug called sunitinib inhibits cell signaling that is involved with tumor cell proliferation and angiogenesis. In this study, sunitinib will be added to the current standard (i.e., non-research) drug treatment regimen for locally advanced or inflammatory breast cancer. Treatment in this study will last about six months. Surgery, which is not a part of this study, is expected to take place about a month after completion of this study treatment. Participants will receive treatment at Seattle Cancer Care Alliance. If hospitalization is needed while in Seattle, participants will be admitted to University of Washington Medical Center. Follow-up may continue for up to five years after treatment has stopped.

Investigator: Jennifer Specht, MD

A Prospective, Randomized, Double-Blind, Stratified, Multicenter, Two-Arm Trial of the Continued Efficacy and Safety of Zoledronic Acid (Zometa) Every Four Weeks vs. Every 12 Weeks in Patients with Documented Bone Metastases from Breast Cancer (NCT00320710)

This clinical study will look at the effectiveness of giving zoledronic acid (Zometa) every four weeks for one year versus every 12 weeks for one year in breast cancer patients with bone metastases who have been pretreated with zoledronic acid. Zoledronic acid is administered by injection to treat hypercalcemia of malignancy, a condition resulting in high calcium blood levels due to cancer. Zoledronic acid is also used to reduce and delay bone complications due to bone metastases from solid tumors. It is used with anti-cancer medicines and is not an anti-cancer therapy. To determine efficacy, we will measure patients’ skeletal related event (SRE) rate during continued treatment in two dosing groups. SREs include bone fracture, radiation therapy or surgery to bone, and spinal cord compression.

Patients in this study have documented bone metastases from breast cancer and have been pretreated with zoledronic acid or pamidronate (Aredia), or all sequential regimens of both agents, for at least nine doses during the first 10 to 15 months of treatment, and are on either zoledronic acid or pamidronate at the time of study entry.

Investigator: Georgiana Ellis, MD

MARIANNE Trial: A Randomized, Three-Arm, Multicenter, Phase III Study to Evaluate the Efficacy and the Safety of T-DM1 Combined with Pertuzumab or T-DM1 Combined with Pertuzumab-Placebo (Blinded For Pertuzumab), Versus the Combination of Trastuzumab Plus Taxane as the First Line Treatment of HER2-Positive Progressive, Recurrent Locally Advanced, or Metastatic Breast Cancer (NCT01120184)

T-DM1 is a conjugate of trastuzumab (Herceptin), the much-used anti-HER2 breast cancer agent, and DM1, a maytansine derivative with potent cytotoxic and mitosis-blocking activity. It is hoped that conjugation will improve cell targeting and reduce toxicity of DM1.

This randomized, three-arm, multicentre study will evaluate the efficacy and safety of T-DM1 with pertuzumab or T-DM1 with pertuzumab-placebo, versus the combination of trastuzumab plus taxane (docetaxel or paclitaxel) in patients with HER2-positive progressive or recurrent locally advanced or previously untreated metastatic breast cancer.

Pertuzumab is a newer monoclonal antibody that inhibits HER2 receptors from pairing with other HER receptors. Patients will be randomly assigned to one of the three treatment arms. We are looking for the response rate, survival rate, and one and two-year survival rates.

Investigator: Julie Gralow, MD

Fanconi Anemia

Gene Transfer for Patients with Fanconi Anemia Complementation Group A (FANCA) (NCT01331018)

This is the world’s first-ever clinical trial of lentiviral vector gene therapy for patients with Fanconi anemia (FA), a very rare inherited disease that primarily affects the bone marrow as well as other organs and tissues. Key advantages of the lentiviral vector (versus previously used gammaretroviral vectors) are its apparent nonmutagenic gene insertion and its shorter incubation period for gene insertion into the patient’s cultured cells.

While allogeneic transplantation is a treatment option for many people with FA, serious toxicities may still occur—especially in patients who lack a matched sibling donor. Researchers hope the new form of gene correction will be a safe and effective alternative for this group of FA patients.

The paramount purpose of this groundbreaking study is to measure safety and, therefore, the FDA has recommended that only adults (>18 years of age) be enrolled initially. Expansion to include children may occur later. The study is initially limited to patients in FA complementation group A (the mutation seen in about two-thirds of cases).

The procedure itself involves autologous transplantation with gene-corrected cells. The lentiviral vector contains the corrected FA gene and is modified to make the vector possibly safer. Enrolled patients undergo stem cell stimulation (with filgrastim and plerixafor) and leukapheresis or, failing mobilization, a bone marrow harvest. The cells are cultured with the gene-containing lentiviral vector and then the genetically modified cells are reinfused. Patients do not receive any conditioning regimen such as those used in allogeneic transplantation. The primary safety and tolerability outcomes will be measured by adverse event monitoring, periodic clinical laboratory testing, and special genetic and cellular analysis of cells.

Trial Sponsor: Hans-Peter Kiem, MD
Investigator: Pamela Becker, MD

Melanoma

Phase II, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy of Vemurafenib in Metastatic Melanoma Patients with Brain Metastases

This is an open-label study to determine the efficacy of vemurafenib in patients with melanoma and brain metastases. Vemurafenib (Zelboraf) is a B-Raf enzyme inhibitor that was approved by the FDA in 2011 for late-stage melanoma treatment. Eligible patients for this trial must have melanoma with the BRAF V600 gene mutation, at least one progressing or untreated lesion in the brain measuring at least 5 cm, performance status zero to one, neurological stability with no requirement for increased steroid during the week prior to starting vemurafenib, and adequate hematologic, renal, cardiac, and liver function. Patients will be ineligible if they have received a prior BRAF or MEK inhibitor.

Treatment cycles with vemurafenib are 28 days. Patients will receive treatment at Seattle Cancer Care Alliance on Day 1 of each cycle (as well as on Day 15 of Cycle 1) for laboratory and clinical assessments, and to receive their supply of study treatment. Study treatment consists of 960 mg vemurafenib orally twice daily with up to two dose reductions for toxicity. Patients are staged every eight weeks to assess response to therapy.

Investigator: Kim Margolin, MD

Hodgkin's and Non-Hodgkin's Lymphoma

Phase II Safety and Efficacy Study of Cal-101 (GS-1101) in Relapsed or Refractory Hodgkin's Lymphoma (NCT01393106)

CAL-101 (GS-1101) is a potent, selective inhibitor of a type of phosphatidylinositol 3 kinase (PI3K) enzyme that is implicated in cancer and inflammatory diseases. In the Phase I trial of this drug, CAL-101 was well tolerated with no dose-limiting toxicity in any of the patients. CAL-101 decreases cellular proliferation and/or cell death in a range of non-Hodgkin's lymphoma (NHL) cell lines. In this open-label, single-arm, Phase II study, patients with histologically confirmed classic Hodgkin's lymphoma will receive CAL-101 in tablet form to be taken twice per day, once in the morning and once in the evening, starting at 150 mg twice per day. Treatment with CAL-101 can continue in responding patients as long as the study is still ongoing and the patients have no excess toxicity from treatment. The primary outcome is overall response rate.

Investigator: Ajay Gopal, MD

Phase II Study to Assess the Efficacy and Safety of Cal-101 (GS-1101) in Indolent B-Cell Non-Hodgkin's Lymphoma Refractory to Rituximab and Alkylating Agents (NCT01282424)

The purpose of this study is to evaluate the efficacy and safety of CAL-101 (GS-1101) in patients with previously treated, indolent (slow-growing) non-Hodgkin's lymphoma (iNHL) that is resistant to rituximab and alkylating-agent chemotherapy. The primary objective will be to assess the overall response rate. CAL-101 is a potent, selective inhibitor of a type of phosphatidylinositol 3 kinase (PI3K) enzyme that is implicated in cancer and inflammatory diseases. In the Phase I trial of this drug, CAL-101 was well tolerated with no dose-limiting toxicity in any of the patients. CAL-101 decreases cellular proliferation and/or cell death in a range of non-Hodgkin's lymphoma cell lines. Eligible patients will be older than 18 years of age and have a histologically confirmed B-cell iNHL. They will receive CAL-101 in tablet form to be taken twice per day, once in the morning and once in the evening. Treatment with CAL-101 can continue in responding patients as long as the study is ongoing and the patients have no excess toxicity from treatment.

Investigator: Ajay Gopal, MD

Renal Cell Carcinoma

Phase II Study of BNC105P in Combination with Everolimus or Following Everolimus for Progressive Metastatic Clear Cell Renal Cell Carcinoma (mRCC) Following Prior Tyrosine Kinase Inhibitors (NCT01034631)

Everolimus has been associated with clinical benefit in patients with metastatic clear cell renal cell carcinoma (mRCC) that has progressed after initial therapy with vascular epidermal growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). There is an unmet need to further improve outcomes in those mRCC patients who have progressed after initial therapy with VEGFR-TKIs.

BNC105P is a vascular disruption agent (VDA) that destabilizes tubulin polymers leading to selective damage of tumor vasculature, hypoxia, and associated tumor necrosis. BNC105P also has a direct antiproliferative action on cancer cells. Up-regulation of the mammalian target of rapamycin (mTOR) pathway has been identified as a survival response by the tumor to hypoxic insult. Thus, the combined use of this VDA with an agent active against mTOR may improve clinical outcomes in patients with progressive mRCC who are refractory to TKIs. This trial aims to validate that hypothesis.

Eligible patients for this trial include those who have been diagnosed with locally advanced or metastatic renal cell carcinoma (RCC) and have progressed on one to two prior VEGFR-TKIs. The Phase I component of the study has been completed and has confirmed that the previously recommended monotherapy dose of BNC105P (16 mg/m2, Days 1 & 8 of a 21-day cycle) is well-tolerated when combined with the approved dose of everolimus (10 mg daily). The randomized Phase II component is now underway and is expected to enroll 134 patients. The BNC105P/everolimus combination will be compared to everolimus alone (standard of care). Additionally, sequential treatment with everolimus monotherapy followed by BNC105P monotherapy at the time of disease progression will also be studied. This will enable a comparison of a combination versus sequential approach.

Investigator: Shailender Bhatia, MD

Referral or Consultation

To discuss your patients’ treatment options with an SCCA physician, please call our intake office at (206) 288-SCCA (7222) or (800) 804-8824. To read the full description of each trial or enroll your patients online, please visit www.seattlecca.org/clinicaltrials.


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