Trial record 1 of 1 for:    NCT02325557
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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. Identifier: NCT02325557
Recruitment Status : Active, not recruiting
First Posted : December 25, 2014
Last Update Posted : March 15, 2018
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Advaxis, Inc.

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.

Condition or disease Intervention/treatment Phase
Cancer Prostate Cancer Drug: ADXS31-142 Drug: ADXS31-142 + Pembrolizumab (MK-3475) Phase 1 Phase 2

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 : Interventional  (Clinical Trial)
Actual Enrollment : 51 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : January 2015
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
U.S. FDA Resources

Arm Intervention/treatment
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.
Drug: ADXS31-142
starting at 1x10^9 cfu IV
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
Drug: ADXS31-142 + Pembrolizumab (MK-3475)
starting at dose from Part A + 200mg of Pembrolizumab

Primary Outcome Measures :
  1. Number of subjects with adverse events in each dose level [ Time Frame: 2 years ]
    Number of subjects with adverse events in each dose level

Secondary Outcome Measures :
  1. 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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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.

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 identifier (NCT number): NCT02325557

United States, California
San Francisco, California, United States
United States, Colorado
University of Colorado Health Sciences Center (UCHSC)
Aurora, Colorado, United States
United States, Maryland
Rockville, Maryland, United States
Towson, Maryland, United States
United States, New Jersey
New Brunswick, New Jersey, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
Philadelphia, Pennsylvania, United States
United States, Rhode Island
Providence, Rhode Island, United States
Sponsors and Collaborators
Advaxis, Inc.
Merck Sharp & Dohme Corp.

Responsible Party: Advaxis, Inc. Identifier: NCT02325557     History of Changes
Other Study ID Numbers: ADXS142-03
First Posted: December 25, 2014    Key Record Dates
Last Update Posted: March 15, 2018
Last Verified: March 2018

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Antineoplastic Agents