Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT03214250
Previous Study | Return to List | Next Study

Safety and Efficacy of APX005M With Gemcitabine and Nab-Paclitaxel With or Without Nivolumab in Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03214250
Recruitment Status : Active, not recruiting
First Posted : July 11, 2017
Last Update Posted : June 14, 2019
Sponsor:
Collaborators:
Bristol-Myers Squibb
Apexigen, Inc.
Cancer Research Institute, New York City
Information provided by (Responsible Party):
Parker Institute for Cancer Immunotherapy

Brief Summary:
The main purposes of this study are to learn how effective the study drug combinations are in treating patients with metastatic pancreatic adenocarcinoma. The drug combinations are APX005M+Nivolumab+Gemcitabine+nab-Paclitaxel, or APX005M+Gemcitabine+nab-Paclitaxel.

Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Adenocarcinoma Drug: APX005M Drug: Nivolumab Drug: Nab-Paclitaxel Drug: Gemcitabine Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 129 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-label, Multicenter, Phase 1b/2 Clinical Study to Evaluate the Safety and Efficacy of CD40 Agonistic Monoclonal Antibody (APX005M) Administered Together With Gemcitabine and Nab-Paclitaxel With or Without PD-1 Blocking Antibody (Nivolumab) in Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma
Actual Study Start Date : July 21, 2017
Estimated Primary Completion Date : July 1, 2022
Estimated Study Completion Date : September 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Gem/NP/nivolumab
Gemcitabine+Nab-Paclitaxel+nivolumab
Drug: Nivolumab
Administer intravenously twice every 28-day cycle
Other Name: Opdivo

Drug: Nab-Paclitaxel
Administer intravenously on 3 times every 28-day cycle
Other Name: Abraxane

Drug: Gemcitabine
Administer intravenously 3 times every 28-day cycle
Other Name: Gemzar

Experimental: Gem/NP/APX005M
Gemcitabine+Nab-Paclitaxel+APX005M
Drug: APX005M
Administer intravenously once every 28-day Cycle

Drug: Nab-Paclitaxel
Administer intravenously on 3 times every 28-day cycle
Other Name: Abraxane

Drug: Gemcitabine
Administer intravenously 3 times every 28-day cycle
Other Name: Gemzar

Experimental: Gem/NP/nivolumab/APX005M
Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M
Drug: APX005M
Administer intravenously once every 28-day Cycle

Drug: Nivolumab
Administer intravenously twice every 28-day cycle
Other Name: Opdivo

Drug: Nab-Paclitaxel
Administer intravenously on 3 times every 28-day cycle
Other Name: Abraxane

Drug: Gemcitabine
Administer intravenously 3 times every 28-day cycle
Other Name: Gemzar




Primary Outcome Measures :
  1. Number and percentage of subjects with adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) [ Time Frame: up to 6 month ]
    Phase 1b Primary Safety Outcome

  2. Overall survival (OS) defined as the time from initiation of study therapy to date of death due to any cause or date of most recent subject contact. [ Time Frame: up to 5 years ]
    Phase 2 Primary Efficacy Outcome


Secondary Outcome Measures :
  1. Objective response rate (ORR) as determined by RECIST criteria [ Time Frame: up to 6 month ]
    Phase 1b and Phase 2 Secondary Efficacy Outcome

  2. Duration of response (DOR) defined as time from first documentation of response (complete response [CR] or partial response [PR]) to first documentation of progressive disease [ Time Frame: up to 6 month ]
    Phase 1b and Phase 2 Secondary Efficacy Outcome

  3. Disease control rate (DCR) is defined as the proportion of subjects who achieve a CR or PR or SD [ Time Frame: up to 6 month ]
    Phase 2 Secondary Efficacy Outcome

  4. Progression free survival (PFS) defined as the time from initiation of study therapy to date of first documented progression of disease, date of death due to any cause or date of most recent subject contact which documented progression free status [ Time Frame: up to 6 month ]
    Phase 2 Secondary Efficacy Outcome



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject has histologically or cytologically documented diagnosis of pancreatic adenocarcinoma with metastatic disease. Locally advanced subjects are not eligible.
  2. Subject must have measureable disease by RECIST 1.1.
  3. Subjects must be age 18 years or older.
  4. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  5. Subjects must have the following laboratory values at screening within 2 weeks of the first dose of investigational agents:

    • Absolute neutrophil count (ANC) ≥1.5 x 109/L (in absence of growth factor support)
    • Platelet count ≥150 x 109/L
    • Hemoglobin ≥9 g/dL(without transfusion support)
    • Serum creatinine ≤1.5 mg/dL, and creatinine clearance ≥ 50 ml/min as measured by Cockcroft and Gault formula
    • Aspartate aminotransferase (AST) and ALT ≤2.5 x upper limit of normal (ULN)
    • Total bilirubin ≤1.5 x ULN, except in subjects with documented Gilbert's Syndrome, who must have a total bilirubin ≤3 x ULN
  6. Women of childbearing potential (WOCBP) must have a negative pregnancy test (serum or urine) within the 7 days prior to study drug administration, and within the 3 days before the first study drug administration, or a negative pregnancy test within the 24 hours before the first study drug administration.
  7. WOCBP and male subjects who are sexually active with WOCBP must agree to use 2 highly effective methods of contraception (including a physical barrier) before the first dose of study drugs, during the study, and for 5 months for women and 7 months for men following the last dose of study drug.
  8. Subjects must have the ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Subject must not have received any prior treatment, including chemotherapy, biological therapy, or targeted therapy for metastatic pancreatic adenocarcinoma, with the following exceptions and notes:

    1. Subjects who have received prior adjuvant therapy for pancreatic adenocarcinoma are eligible if neoadjuvant and adjuvant therapy (including chemotherapy and/or radiotherapy) was fully completed more than 4 months before the start of study treatment. In this case, prior Gem and/or NP is allowable
    2. Prior resection surgery is allowable.
    3. Patients initially diagnosed with locally advanced pancreatic cancer who have undergone chemotherapy then resection and were with no evidence of disease are eligible if metastatic relapse of disease has occurred and if the last dose of chemotherapy was more than 4 months before the data of study entry.
  2. Subjects must not have another active invasive malignancy, with the following exceptions and notes:

    1. History of a non-invasive malignancy, such as cervical cancer in situ, non-melanomatous carcinoma of the skin, in situ melanoma, or ductal carcinoma in situ of the breast, is allowed.
    2. History of malignancy that is in complete remission after treatment with curative intent is allowed.
    3. No current or history of a hematologic malignancy is allowed, including subjects who have undergone a bone marrow transplant.
  3. History of clinically significant sensitivity or allergy to monoclonal antibodies, their excipients, or intravenous gamma globulin
  4. Previous exposure to CD40, PD-1, PD-L1, CTLA-4 antibodies or any other immunomodulatory agent
  5. History of (non-infectious) pneumonitis that required corticosteroids or current pneumonitis, or history of interstitial lung disease
  6. Subjects must not have a known or suspected history of an autoimmune disorder, including but not limited to inflammatory bowel disease, celiac disease, Wegner syndrome, Hashimoto syndrome, systemic lupus erythematosus, scleroderma, sarcoidosis, or autoimmune hepatitis, within 3 years of the first dose of investigational agent, except for the following.

    a. Subjects with Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders such as vitiligo, or alopecia not requiring systemic therapy, or conditions not expected to recur in the absence of an external trigger are eligible.

  7. Subjects must not have an uncontrolled intercurrent illness, including an ongoing or active infection, current pneumonitis, symptomatic congestive heart failure (New York Heart Association class III or IV), unstable angina, uncontrolled hypertension, cardiac arrhythmia, interstitial lung disease, active coagulopathy, or uncontrolled diabetes.
  8. Subjects must not have a history of myocardial infarction within 6 months or a history of arterial thromboembolic event within 3 months of the first dose of investigational agent.
  9. Subjects must not have a history of human immunodeficiency virus, hepatitis B, or hepatitis C, except for the following:

    1. subjects with anti-hepatitis B core antibody but with undetectable HBV DNA and negative for HBsAg
    2. subjects with resolved or treated HCV (i.e. HCV antibody positive but undetectable HCV RNA)
  10. Subjects must not have a history of primary immunodeficiency.
  11. Subjects must not receive concurrent or prior use of an immunosuppressive agent within 14 days of the first dose of investigational agent, with the following exceptions and notes:

    1. Systemic steroids at physiologic doses (equivalent to dose of oral prednisone 10 mg) are permitted. Steroids as anti-emetics for chemotherapy are not allowed.
    2. Intranasal, inhaled, topical, intra-articular, and ocular corticosteroids with minimal systemic absorption are permitted.
    3. Subjects with a condition with anticipated use of systemic steroids above the equivalent of 10 mg prednisone are excluded.
  12. Subjects must not have a history of clinically manifested central nervous system (CNS) metastases.

    a. Subjects with known or suspected leptomeningeal disease or cord compression are not eligible.

  13. Subjects must not have had major surgery as determined by the PI within 4 weeks before the first dose of investigational agent.
  14. Subjects must not have received another investigational agent within the shorter of 4 weeks or 5 half-lives before the first dose of investigational agent.
  15. Subjects must not have received a live attenuated vaccine within 28 days before the first dose of investigational agent, and subjects, if enrolled, should not receive live vaccines during the study or for 180 days after the last dose of investigational agent.
  16. Females who are pregnant or lactating or who intend to become pregnant during participation in the study are not eligible to participate.
  17. Subjects who are of reproductive potential who refuse to use effective methods of birth control during the course of participation of the study and within 5 month for women and 7 months for men of the last dose of investigational agent are ineligible to participate in the study.
  18. Subjects who have any clinically significant psychiatric, social, or medical condition that, in the opinion of the investigator, could increase the subject's risk, interfere with protocol adherence, or affect the subject's ability to give informed consent are ineligible to participate in the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03214250


Locations
Layout table for location information
United States, California
University of California, Los Angeles
Los Angeles, California, United States, 90095
University of California, San Francisco
San Francisco, California, United States, 94143
Stanford University
Stanford, California, United States, 94305
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Pennsylvania
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Parker Institute for Cancer Immunotherapy
Bristol-Myers Squibb
Apexigen, Inc.
Cancer Research Institute, New York City
Investigators
Layout table for investigator information
Principal Investigator: Robert H Vonderheide, MD University of Pennsylvania

Publications:

Layout table for additonal information
Responsible Party: Parker Institute for Cancer Immunotherapy
ClinicalTrials.gov Identifier: NCT03214250     History of Changes
Other Study ID Numbers: PICI0002
UPCC 11217 ( Other Identifier: University of Pennsylvania )
First Posted: July 11, 2017    Key Record Dates
Last Update Posted: June 14, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Parker Institute for Cancer Immunotherapy:
Nivolumab
APX005M
previously untreated metastatic pancreatic adenocarcinoma
Gemcitabine
nab-Paclitaxel
Additional relevant MeSH terms:
Layout table for MeSH terms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Paclitaxel
Albumin-Bound Paclitaxel
Nivolumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological