Clinical Trial 18803

Cancer Type: Gynecological Tumor
Interventions:Avastin (Bevacizumab); Bevacizumab; CA4P (fosbretabulin); Doxil (doxorubicin liposome); Placebo; Taxol (paclitaxel); doxorubicin liposome; paclitaxel

Study Type: Treatment
Phase of Study: Phase II/III
Investigators:


    Overview

    Study Title

    FOCUS: A Multicenter, Multinational, Double-Blind, 2-Arm, Randomized, Phase 2/3, Study of Physician's Choice Chemotherapy ([PCC] Weekly Paclitaxel or Pegylated Liposomal Doxorubicin [PLD]) Plus Bevacizumab and CA4P Versus PCC Plus Bevacizumab and Placebo for Subjects with Platinum-Resistant, Recurrent Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancer

    Summary

    The purpose of this study is to see if the addition of CA4P to the standard chemotherapy will increase the amount of time the participant's cancer stays in check, or in other words the amount of time their cancer is progression free. Other things that will be looked at are: how much, if any, their cancer shrinks; how well participant's feel during the study; their quality of life outlook; and, changes in cancer specific markers in their blood.

    Objective

    The main objective of the study is to demonstrate an improvement in PFS with standard PCC regimens (weekly paclitaxel or PLD) plus bevacizumab and CA4P compared with PCC plus bevacizumab and placebo. The secondary objectives of this study are: * Improvement in ORR (by RECIST and/or CA-125 criteria). * Evaluation of OS. * Assessment of the proportion of subjects who remain progression-free at 6, 9, and 12 months on the regimen of PCC plus bevacizumab and CA4P compared with PCC plus bevacizumab and placebo. * To evaluate the safety and tolerability, as measured by physical exams, vital signs, laboratory measures, ECOG PS and incidence of AEs using NCI CTCAE version 4.03, of PCC plus bevacizumab and CA4P compared with PCC plus bevacizumab and placebo.

    Inclusion Criteria

  • Signed informed consent form (ICF)
  • Women Age ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) PS of 0-1
  • Histologically or cytologically-confirmed epithelial ovarian, fallopian tube or primary peritoneal cancer in recurrent stage
  • prOC (platinum-resistant ovarian cancers) defined as progression within >1 to less than 6 months of receiving last platinum-based therapy
  • Received ≥ 1 but ≤ 2 prior platinum-based regimens
  • Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Left ventricular ejection fraction (LVEF) greater than or equal to at least 45% at baseline assessment if participant is receiving Pegylated Liposomal Doxorubicin (PLD), and/or anthracycline is a concomitant medication
  • No evidence of active (progressing) brain metastasis. (Treated brain metastasis allowed with a post-treatment magnetic resonance imaging (MRI) or Computed Tomography (CT) of brain showing no active (progressing) brain metastasis). Treatment of brain metastasis may include surgery, radiosurgery (linear accelerator (LINAC), gamma knife), or whole brain irradiation. Surgery for brain metastasis must be > 8 weeks from study entry.
  • Adequate bone marrow, hepatic and renal function
  • Participants of childbearing potential must have a negative serum pregnancy test prior to study entry and must be practicing an effective form of contraception
  • At least 2 weeks since prior radiotherapy and has recovered from any Grade 3 toxicities
  • Life expectancy ≥ 12 weeks

  • Exclusion Criteria

  • Known hypersensitivity to any of the study drugs
  • Have received prior CA4P therapy
  • Previously having failed treatment with bevacizumab combined with the intended Physician's Choice Chemotherapy (PCC)
  • Previous treatment with greater than 2 anti-cancer treatment regimens
  • Untreated brain metastasis or leptomeningeal brain metastasis
  • Solid organ or bone marrow transplant
  • Platinum-refractory disease (defined as progression during or within one (1) month of completing a previous platinum-containing regimen)
  • > Grade 2 peripheral neuropathy
  • Current thrombotic or hemorrhagic disorder/event or history of prior event within 6 months of start of Screening
  • History of prior cerebrovascular event, (including transient ischemic attack) within 6 months of start of Screening
  • Recent history of angina pectoris, myocardial infarction, or NYHA Class III and IV congestive heart failure
  • History of torsade de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia, heart block (excluding 1st degree block, benign PR interval prolongation only), congenital long QT syndrome or new ST segment elevation or depression or new Q wave on ECG
  • Known uncontrolled HIV infection
  • Uncontrolled, clinically significant active infection
  • Serious non-healing wound, ulcer or bone fracture
  • Known hypersensitivity to any of the components of CA4P, paclitaxel, PLD, or bevacizumab (paclitaxel and PLD dependent on whether Principal Investigator (PI) plans they will be dosed with that PCC)
  • Currently or planning on receiving concurrent investigational therapy or who have received investigational therapy for any indication within 30 days of the first scheduled day of dosing
  • Any other intercurrent medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the ability to provide informed consent, cooperate and participate in the study, or to interfere with the interpretation of the study results
  • Other invasive malignancies, with the exception of non-melanoma skin cancer, or previous cancer treatment that contraindicates this protocol therapy
  • Prior radiation therapy to the pelvis or abdomen within 4 weeks of entry into the study
  • History of fistula, gastrointestinal (GI) perforation or intra-abdominal abscess
  • Uncontrolled hypertension
  • Uncontrolled elevated proteinuria levels in the investigator's opinion
  • Corrected QT interval ([QTc] Fridericia) > 480 ms
  • Significant vascular disease or recent peripheral arterial thrombosis
  • Active bleeding or pathologic conditions that carry high risk of bleeding
  • Pregnant or lactating