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A Study Evaluating the Safety and Pharmacokinetics of DMUC4064A in Participants With Platinum-Resistant Ovarian Cancer or Unresectable Pancreatic Cancer

NCT02146313

Description:

This is a Phase 1, multicenter, open-label, dose-escalation study of DMUC4064A administered by intravenous (IV) infusion every three weeks (q3w) to cancer participants. The study will employ a traditional 3 + 3 dose escalation design to determine the maximum tolerated dose (MTD) of DMUC4064A against platinum-resistant ovarian cancer. Once a q3w recommended Phase 2 dose (RP2D) is identified, two expansion cohorts (one in platinum-resistant ovarian cancer and another in unresectable pancreatic cancer) may be evaluated to further characterize the safety and activity in these populations.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Malignant Ovarian Epithelial Tumor
  • Pancreatic Ductal Adenocarcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating the Safety and Pharmacokinetics of DMUC4064A in Patients With Platinum-Resistant Ovarian Cancer or Unresectable Pancreatic Cancer
  • Official Title: A Phase I, Open-Label, Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of DMUC4064A Administered Intravenously to Patients With Platinum-Resistant Ovarian Cancer or Unresectable Pancreatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: GO29213
  • NCT ID: NCT02146313

Conditions

  • Ovarian Cancer, Pancreatic Cancer

Interventions

DrugSynonymsArms
DMCU4064ADose-escalation cohort
DMUC4064ADose-expansion cohort

Purpose

This is a Phase I, multicenter, open-label, dose-escalation study of DMUC4064A administered by intravenous (IV) infusion every three weeks (q3w) to cancer patients. The study will employ a traditional 3 + 3 dose escalation design to determine the maximum tolerated dose (MTD) of DMUC4064A against platinum-resistant ovarian cancer. Once a q3w recommended phase II dose (RP2D) is identified, two expansion cohorts (one in platinum-resistant ovarian cancer and another in unresectable pancreatic cancer) may be evaluated to further characterize the safety and activity in these patient populations. Time on treatment is expected to last approximately 1 year.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Dose-escalation cohortExperimental
  • DMCU4064A
    Dose-expansion cohortExperimental
      • DMUC4064A

    Eligibility Criteria

    Inclusion Criteria:

    - Age >/= 18 years

    - Life expectancy of at least 12 weeks

    - ECOG Performance Status of 0 or 1

    - Measurable disease is defined as at least one bi-dimensionally measurable non-lymph node lesion >/= 1 cm on long access diameter on CT or MRI scan OR at least one bi-dimensionally measureable lymph node measuring >/= 1.5 cm on short access diameter on CT or MRI scan

    - Adequate hematologic, liver, and renal function

    - Highly effective contraception as defined by the protocol

    Patients with Ovarian Cancer

    - Histological documentation of epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.

    - Documented MUC16 expression (by CA125 or IHC)

    - Disease that has progressed or relapsed during or within 6 months after the most recent treatment with a platinum-containing chemotherapy regimen.

    - Progression or relapse from prior platinum-based chemotherapy must be documented radiographically by RECISTv1.1 criteria

    For ovarian cancer dose expansion cohorts only:

    - Not more than two prior chemotherapy regimens for the treatment of platinum-resistant ovarian cancer

    - Archival or fresh tumor tissue demonstrating MUC16 expression by central review (by IHC)

    Patients with Pancreatic Cancer

    - Histologic documentation of incurable, locally advanced, or metastatic pancreatic ductal adenocarcinoma consisting of unresectable pancreatic ductal adenocarcinoma (i.e., patients who are not considered eligible for surgical resection with curative intent), including recurrence of previously resected disease.

    - Documented MUC16 expression

    - Patients for whom no further standard of care therapy exists, must have received standard of care chemotherapy in the adjuvant or advanced/metastatic setting

    - No more than two prior chemotherapy regimens administered for the treatment of pancreatic cancer in the adjuvant or advanced/metastatic setting

    Exclusion Criteria:

    - Anti-tumor therapy, including chemotherapy, biologic, experimental, or hormonal therapy within 4 weeks prior to Day 1

    - Prior treatment with MUC16 targeted therapy (e.g., oregovomab [OvaRex] or abagovomab) including DMUC5754A or with an MMAE-containing ADC

    - Palliative radiation to bone metastases within 2 weeks prior to Day 1

    - Prior radiation to lung fields

    - Major surgical procedure within 4 weeks prior to Day 1

    - Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (including HIV and atypical mycobacterial disease but excluding fungal infections of the nail beds) at study enrollment or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1, Day 1

    - Evidence of significant uncontrolled concomitant diseases, such as cardiovascular disease; nervous system, renal, hepatic, endocrine, or gastrointestinal disorders; autoimmune disease, or a serious non-healing wound or fracture

    - Clinically significant pulmonary symptoms and signs, any active pulmonary or respiratory infection at enrollment, pulmonary infiltrates on screening CT scan of the chest that are associated with symptoms (including dyspnea), resting or exercise SpO2 < 90%, requirement for supplementary oxygen at rest or exercise (either continuously or intermittently), moderate (40% - 60% predicted) or severe (< 40% predicted) decreased DLCO or mild (> 60% </= LLN % predicted) decrease with clinically significant symptoms)

    - Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis

    - Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix, squamous carcinoma of the skin, adequately controlled limited basal cell skin cancer, or synchronous primary endometrial cancer or prior primary endometrial cancer if protocol criteria are met

    - Untreated or active central nervous system (CNS) metastases. Patients with a history of treated CNS metastases may be eligible

    - Current Grade > 1 toxicity (except alopecia and anorexia) from prior therapy or Grade > 1 neuropathy from any cause

    - History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)

    - Pregnancy or breastfeeding

    - Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications

    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Incidence of dose-limiting toxicities (DLTs)
    Time Frame:Days 1 to 21
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Objective response according to response evaluation criteria in solid tumors (RECIST)
    Time Frame:Approximately 1 year
    Safety Issue:
    Description:
    Measure:Duration of objective response
    Time Frame:Up to 1 year
    Safety Issue:
    Description:
    Measure:Progression-free survival
    Time Frame:Up to 1 year
    Safety Issue:
    Description:
    Measure:Incidence of anti-DMUC4064A antibodies
    Time Frame:Approximately 1 year
    Safety Issue:
    Description:
    Measure:Area under the concentration curve (AUC) of DMUC4064A
    Time Frame:Approximately 1 year
    Safety Issue:
    Description:

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Genentech, Inc.

    Trial Keywords

      Last Updated

      September 1, 2016