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A Dose Escalation and Confirmation Study of PT-112 in Advanced Solid Tumors in Combination With Avelumab (PAVE-1)

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ClinicalTrials.gov Identifier: NCT03409458
Recruitment Status : Recruiting
First Posted : January 24, 2018
Last Update Posted : September 17, 2018
Sponsor:
Collaborators:
Pfizer
EMD Serono
Information provided by (Responsible Party):
Phosplatin Therapeutics

Brief Summary:
This is a Phase 1b/2a, open-label, multi-center, non-randomized, dose-escalation study of PT-112 in combination with the anti-PD-L1 antibody, avelumab, in selected advanced solid tumors. The study is to be conducted in two parts: the Dose Escalation Phase of PT-112 within the combination and the Dose Confirmation Phase. The Dose Escalation Phase will determine the Maximum Tolerated Dose (MTD) and recommended Phase 2 dose (RP2D) of PT-112 in the combination as avelumab will be administered at a flat dose of 800 mg. The trial will evaluate the PK (pharmacokinetic) effects of PT-112 and the safety and tolerability of the combination as well as preliminary clinical effects. The Dose Confirmation Phase will consist of two additional cohorts in patients with non-small cell lung cancer or urothelial carcinoma who will be treated at or below the MTD of PT-112 in the combination.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer (NSCLC) Urothelial Carcinoma (UC) Squamous Cell Carcinoma of the Head and Neck (SCCHN) Metastatic Breast Cancer (mBC) Castration-resistant Prostate Cancer (CRPC) Drug: PT-112 Biological: avelumab Phase 1 Phase 2

Detailed Description:
This is a Phase 1b/2a, open-label, multi-center, non-randomized, dose-escalation study of PT-112 in combination with the anti-PD-L1 antibody, avelumab, in selected advanced solid tumors. The study is to be conducted in two parts: the Dose Escalation Phase of PT-112 within the combination and the Dose Confirmation Phase. The Dose Escalation Phase will determine the Maximum Tolerated Dose (MTD) and recommended Phase 2 dose (RP2D) of PT-112 in the combination as avelumab will be administered at a flat dose of 800 mg. The trial will evaluate the PK (pharmacokinetic) effects of PT-112 and the safety and tolerability of the combination as well as preliminary clinical effects. The Dose Confirmation Phase will consist of two additional cohorts in patients with non-small cell lung cancer or urothelial carcinoma who will be treated at or below the MTD of PT-112 in the combination.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2a Dose Escalation and Confirmation Study of PT-112 in Advanced Solid Tumors in Combination With Avelumab
Actual Study Start Date : April 24, 2018
Estimated Primary Completion Date : February 1, 2020
Estimated Study Completion Date : May 1, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Avelumab

Arm Intervention/treatment
Experimental: PT-112 in combination with avelumab

PT-112, administered by intravenous infusion avelumab, administered by intravenous infusion

Patients with all listed conditions are eligible for treatment during the dose escalation phase of the study. Patients with NSCLC and mUC are eligible for the dose confirmation phase of the study.

Drug: PT-112
The MTD and RP2D of PT-112 when used in combination with avelumab will be determined during dose escalation.

Biological: avelumab
Avelumab will be administered at a fixed dose of 800 mg.




Primary Outcome Measures :
  1. Recommended dose (RD) of PT-112 to be used in combination with avelumab for further studies in patients with advanced solid tumors. [ Time Frame: 24 months ]

Secondary Outcome Measures :
  1. Peak Plasma concentration (Cmax) for PT-112 Injection [ Time Frame: 24 months ]
  2. Area under the plasma concentration versus time curve (AUC) for PT-112 Injection [ Time Frame: 24 months ]
  3. Dose-limiting toxicities (DLTs) [ Time Frame: 24 months ]
  4. Number of patients with Adverse Events (AEs) [ Time Frame: 24 months ]
  5. Tumor burden Assessment [ Time Frame: 24 months ]
    To be assessed by irRECIST criteria for NSCLC, SCCHN, mBC, and UC patients and by Prostate Cancer Working Group 3 (PCWG3) criteria for patients with CRPC

  6. Overall Response Rate (ORR) [ Time Frame: 24 months ]
  7. Disease Control Rate (DCR) [ Time Frame: 24 months ]
  8. Median Progression-free Survival (mPFS) [ Time Frame: 24 months ]


Information from the National Library of Medicine

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

Key Inclusion Criteria:

  1. Histologically or cytologically proven metastatic or locally advanced disease. Specifically:

    • patients with NSCLC, UC, mBC, or SCCHN must have measurable disease by RECIST v1.1 criteria with at least one uni-dimensional measurable lesion;
    • patients with CRPC must meet PCWG3 criteria for disease progression at trial entry
  2. Availability of tumor specimens is mandatory for patients in the confirmation phase;

2 ECOG Performance Status (PS) 0-1; 4 Estimated Life Expectancy > 3 months; 5 Adequate bone marrow (BM), renal, hepatic and metabolic function;

Key Exclusion Criteria:

  1. Concurrent cancer treatment with cytoreductive therapy, radiotherapy, cytokine therapy, cytotoxic agents, targeted small molecule therapy or any investigational anticancer small molecule drugs within 2 weeks prior to the start of study treatment (except 5 weeks from last dose of nitrosourea compound) OR treatment with monoclonal antibodies within 4 weeks prior to the start of study treatment, with the following exceptions:

    • PD-1 / PD-L1 checkpoint inhibitor therapy is permitted;
    • Palliative bone-directed radiotherapy is permitted unless involving an area of ≥ 25% of bone marrow reserves and occurring within 5 weeks prior to the start of study treatment;
    • Erythropoietin and darbopoietin-α are permitted;
    • Hormonal therapies acting on the hypothalamic-pituitary-gonadal axis (i.e., LHRH agonist/antagonist) are permitted. No other hormonal therapy is permitted;
  2. Known symptomatic central nervous system (CNS) metastases requiring steroids. Patients with previously diagnosed CNS metastases are eligible if they (1) have completed their treatment and have recovered from the acute effects of radiation therapy and/or surgery prior to enrollment, (2) have discontinued corticosteroid treatment for these metastases for at least 14 days, and (3) are neurologically stable;
  3. Diagnosis of any other malignancy within 2 years prior to enrollment. However, adequately treated basal cell or squamous cell skin cancer or non-invasive superficial bladder cancer or carcinoma in situ of the bladder, breast or cervix; or prostate cancer of low grade (Gleason ≤6) or surveillance without any plans for treatment intervention (e.g., surgery, radiation, or castration) are allowed;
  4. Vaccination within 4 weeks of the first dose of study treatment is prohibited except for administration of inactivated vaccines;
  5. Current use of immunosuppressive medication at study entry, with the following exceptions:

    • Intranasal, inhaled, or topical steroids or local steroid injections (eg, intra-articular injection) are permitted;
    • Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or equivalent are permitted;
    • Steroids as premedication for hypersensitivity reactions are permitted;
  6. Active or prior autoimmune disease that might deteriorate with receiving an immunostimulatory agent. However, patients with diabetes type 1, vitiligo, psoriasis, or hypo- or hyper-thyroid disease not requiring immunosuppressive treatment are eligible;
  7. Acute or chronic infections requiring systemic therapy, including, among others:

    • Active infection requiring systemic therapy;
    • History of testing positive to human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome;
    • Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test is positive);
    • Active tuberculosis (history of exposure or history of positive TB test with presence of clinical symptoms, physical or radiographic finding);
  8. Known history of autoimmune colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis;
  9. Known intolerance to checkpoint inhibitor therapy, defined by the occurrence of an AE leading to drug discontinuation;
  10. Participation in other studies involving investigational drug(s) within 28 days prior to study entry and/or during study participation;

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): NCT03409458


Contacts
Contact: Danae Hudson (919) 867-1616 ext 1616 dhudson@clinipace.com

Locations
United States, Arizona
Mayo Clinic Recruiting
Phoenix, Arizona, United States, 85054
Contact: TBD TBD         
Principal Investigator: Alan H. Bryce, MD         
United States, Colorado
University of Colorado Cancer Center Recruiting
Aurora, Colorado, United States, 80045
Principal Investigator: Ross Camidge, MD         
United States, Florida
Mayo Clinic Recruiting
Jacksonville, Florida, United States, 32224
Principal Investigator: Roxana Dronca, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Principal Investigator: Brian Costello, MD         
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: TBD TBD         
Principal Investigator: Daniel D. Karp, MD         
Sponsors and Collaborators
Phosplatin Therapeutics
Pfizer
EMD Serono
Investigators
Principal Investigator: Daniel D Karp, MD M.D. Anderson Cancer Center

Responsible Party: Phosplatin Therapeutics
ClinicalTrials.gov Identifier: NCT03409458     History of Changes
Other Study ID Numbers: PT-112-103-PAVE-1
First Posted: January 24, 2018    Key Record Dates
Last Update Posted: September 17, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Phosplatin Therapeutics:
Advanced Solid Tumors
NSCLC
mUC
mBC
CRPC
SCCHN

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Prostatic Neoplasms
Head and Neck Neoplasms
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neoplasms, Squamous Cell
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Prostatic Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs