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ADXS31-142 Alone and in Combination With Pembrolizumab (MK-3475) in Patients With Prostate Cancer - KEYNOTE-046

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: NCT02325557
Recruitment Status : Active, not recruiting
First Posted : December 25, 2014
Last Update Posted : March 12, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Advaxis, Inc.

Tracking Information
First Submitted Date  ICMJE December 22, 2014
First Posted Date  ICMJE December 25, 2014
Last Update Posted Date March 12, 2020
Actual Study Start Date  ICMJE January 2015
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 22, 2014)
Number of subjects with adverse events in each dose level [ Time Frame: 2 years ]
Number of subjects with adverse events in each dose level
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 18, 2016)
Progression Free Survival as measured by RECIST 1.1 or ir RECIST [ Time Frame: 2 years ]
Progression Free Survival as measured by RECIST 1.1 or ir RECIST
Original Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2014)
Number of subjects with progression free survival [ Time Frame: 2 years ]
Number of subjects with progression free survival
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ADXS31-142 Alone and in Combination With Pembrolizumab (MK-3475) in Patients With Prostate Cancer - KEYNOTE-046
Official Title  ICMJE A Phase 1-2 Dose-Escalation and Safety Study of ADXS31-142 Alone and of ADXS31-142 in Combination With Pembrolizumab (MK-3475) in Patients With Previously Treated Metastatic Castration-Resistant Prostate Cancer
Brief Summary A Phase 1/2 multicenter, dose determining, open-label study of ADXS31-142 monotherapy and a combination of ADXS31-142 with Pembrolizumab (MK-3475) in patients with metastatic castration-resistant prostate cancer. Part A will be dose-determining of ADXS31-142 monotherapy. Part B will be dose-determining of ADXS31-142 and Pembrolizumad (MK-3475) in combination. Part B expansion will treat additional patients with the recommended dose from Part B.
Detailed Description

Part A of the study will be an open-label, Phase 1, multicenter, non-randomized, dose-determining trial of ADX31-142 monotherapy in subjects with metastatic castration-resistant prostate cancer (mCRPC). The dose determining phase is intended to select a recommended Phase 2 dose (RP2D) for Part B.

Part B of the study will be an open-label, Phase 1-2, multicenter, non-randomized dose-determining trial of ADXS31-142 in combination with pembrolizumab (MK-3475) in subjects with mCRPC. Part B will consist of a dose-determination phase followed by an expansion cohort phase. The dose-determining phase is intended to select a RP2D for the combination.

Dose escalation/de-escalation for this study will be explored by applying the mTPI design.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cancer
  • Prostate Cancer
Intervention  ICMJE
  • Drug: ADXS31-142
    starting at 1x10^9 cfu IV
  • Drug: ADXS31-142 + Pembrolizumab (MK-3475)
    starting at dose from Part A + 200mg of Pembrolizumab
Study Arms  ICMJE
  • Experimental: Part A
    Patients will receive ADXS31-142 monotherapy. Dosing will start at 1 x 10^9 cfu IV and escalate to 1 x 10^10 if appropriate.
    Intervention: Drug: ADXS31-142
  • Experimental: Part B/Expansion
    Patients will receive ADXS31-142 and pembrolizumab (MK-3475) in combination. Dosing of ADXS31-142 will start at one dose level less that appropriate in Part A in combination with 200 mg of pembrolizumab. Dosing of ADXS31-142 will be escalated if appropriate
    Intervention: Drug: ADXS31-142 + Pembrolizumab (MK-3475)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 22, 2014)
51
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Be willing and able to provide written informed consent for the trial.
  2. Be 18 years of age or older on day of signing informed consent.
  3. Have progressive metastatic castration resistant prostate cancer, on androgen deprivation therapy, based on as least one of the following criteria:

    1. PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval with a minimum PSA of 2 ng/ml.
    2. Progression of bi-dimensionally measurable soft tissue (nodal metastasis) assessed within 1 month prior to registration by a CT scan or MRI of the abdomen and pelvis.
    3. Progression of bone disease (evaluable disease) (new bone lesion(s)) by bone scan.
  4. Has discontinued antiandrogens (bicalutamide, nilutamide) >6 weeks and enzalutamide >4 weeks prior to Day 1 of trial treatment
  5. Have a performance status of 0 or 1 on the ECOG Performance Scale.

Exclusion Criteria:

  1. Received more than 3 prior systemic treatment regimens with chemotherapy , hormonal, or immunotherapy in the metastatic setting or received more than 1 prior chemotherapeutic regimen in the metastatic setting
  2. Has a diagnosis of immunodeficiency or is receiving any systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Day 1 of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
  3. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  4. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤Grade 1 or at baseline) from adverse events due to a previously administered agent.
  5. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or if the patient has previously participated in a Merck MK-3475 clinical trial.
  6. Has a contraindication to administration of ampicillin or trimethoprim/ sulfamethoxazole.
  7. Has implanted medical device(s) that pose a high risk for colonization and/or cannot be easily removed (e.g., prosthetic joints, artificial heart valves, pacemakers, orthopedic screw(s), metal plate(s), bone graft(s), or other exogenous implant(s)). NOTE: More common devices and prosthetics which include arterial and venous stents, dental and breast implants, and venous access devices (e.g., Port-a-Cath or Mediport) are permitted. Sponsor must be contacted prior to consenting any subject who has any other device and/or implant.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02325557
Other Study ID Numbers  ICMJE ADXS142-03
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Advaxis, Inc.
Study Sponsor  ICMJE Advaxis, Inc.
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE Not Provided
PRS Account Advaxis, Inc.
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP