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Study to Evaluate the Safety and Tolerability of Avelumab in Combination With Other Anti-Cancer Therapies in Patients With Advanced Malignancies

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ClinicalTrials.gov Identifier: NCT03217747
Recruitment Status : Recruiting
First Posted : July 14, 2017
Last Update Posted : May 1, 2018
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

Objectives:

Primary Objectives:

  • For Arms D-G, to establish the safety, tolerability, and dose-limiting toxicities (DLTs) of different treatment combinations of avelumab when administered in combination with checkpoint agonist(s) with or without radiation, or radiation and cisplatin in patients with limited, locally advanced or metastatic solid tumors in order to estimate the maximum tolerated dose (MTD) and select the recommended phase 2 dose (RP2D).
  • To correlate pre- and post-treatment CD8 expression with clinical benefit (complete response [CR], partial response [PR], or stable disease [SD] for > 6 months).

Secondary Objectives:

  • To evaluate the efficacy of the different treatment combinations in patients with limited, locally advanced or metastatic solid tumors by assessing objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and immune-related RECIST (irRECIST).
  • To evaluate the efficacy of the different treatment combinations in patients with limited, locally advanced or metastatic solid tumors by assessing progression-free survival (PFS), duration of response (DOR), and overall survival (OS).

Condition or disease Intervention/treatment Phase
Malignant Neoplasm of Breast Malignant Neoplasms of Bone and Articular Cartilage Malignant Neoplasms of Digestive Organs Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System Malignant Neoplasms of Female Genital Organs Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites Malignant Neoplasms of Independent (Primary) Multiple Sites Malignant Neoplasms of Lip Oral Cavity and Pharynx Malignant Neoplasms of Male Genital Organs Malignant Neoplasms of Mesothelial and Soft Tissue Malignant Neoplasms of Respiratory and Intrathoracic Organs Malignant Neoplasms of Thyroid and Other Endocrine Glands Malignant Neoplasms of Urinary Tract Neoplasms of Uncertain or Unknown Behavior Drug: Avelumab Drug: Utomilumab Drug: PF-04518600 Radiation: Radiation Drug: Cisplatin Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 188 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study to Evaluate the Safety and Tolerability of Avelumab in Combination With Other Anti-Cancer Therapies in Patients With Advanced Malignancies
Actual Study Start Date : August 2, 2017
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Avelumab

Arm Intervention/treatment
Experimental: Arm A: Avelumab and Utomilumab

Utomilumab 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Avelumab 10 mg/kg by vein every 2 weeks starting Cycle 3 Day 1.

Treatment cycles are 28 days.

Drug: Avelumab

Arm A: Avelumab 10 mg/kg by vein every 2 weeks starting Cycle 3 Day 1.

Arm B: Avelumab 10 mg/kg by vein every 2 weeks starting Cycle 3 Day 1.

Arm C Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm D Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm E Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm F Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm G Phase I Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm G Phase II Starting Dose of Avelumab: MTD from Phase I.

Other Name: MSBOO10718C

Drug: Utomilumab

Arm A: Utomilumab 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Arm C Phase I and II Starting Dose of Utomilumab: 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Arm D Phase I and II Starting Dose of Utomilumab: 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Arm F Phase I and II Starting Dose of Utomilumab: 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Other Names:
  • PF-05082566
  • Anti-CD137

Experimental: Arm B: Avelumab and PF-04518600

PF-04518600 0.3 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Avelumab 10 mg/kg by vein every 2 weeks starting Cycle 3 Day 1.

Treatment cycles are 28 days.

Drug: Avelumab

Arm A: Avelumab 10 mg/kg by vein every 2 weeks starting Cycle 3 Day 1.

Arm B: Avelumab 10 mg/kg by vein every 2 weeks starting Cycle 3 Day 1.

Arm C Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm D Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm E Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm F Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm G Phase I Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm G Phase II Starting Dose of Avelumab: MTD from Phase I.

Other Name: MSBOO10718C

Drug: PF-04518600

Arm B: PF-04518600 0.3 mg/kg by vein every 2 weeks starting Cycle 1 Day 1. Arm C Phase I Starting Dose of PF-04518600: 0.1 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm C Phase II Starting Dose of PF-04518600: Maximum tolerated dose (MTD) from Phase I.

Arm E Phase I and II Starting Dose of PF-04518600 to be determined, given by vein every 2 weeks starting Cycle 1 Day 1.

Arm F Phase I and II Starting Dose of PF-04518600: MTD from Arm C by vein every 2 weeks starting Cycle 1 Day 1.


Experimental: Arm C: Avelumab, Utomilumab and PF-04518600

Phase I Starting Dose of PF-04518600: 0.1 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Phase II Starting Dose of PF-04518600: Maximum tolerated dose (MTD) from Phase I.

Phase I and II Starting Dose of Utomilumab: 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Treatment cycles are 28 days.

Drug: Avelumab

Arm A: Avelumab 10 mg/kg by vein every 2 weeks starting Cycle 3 Day 1.

Arm B: Avelumab 10 mg/kg by vein every 2 weeks starting Cycle 3 Day 1.

Arm C Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm D Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm E Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm F Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm G Phase I Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm G Phase II Starting Dose of Avelumab: MTD from Phase I.

Other Name: MSBOO10718C

Drug: Utomilumab

Arm A: Utomilumab 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Arm C Phase I and II Starting Dose of Utomilumab: 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Arm D Phase I and II Starting Dose of Utomilumab: 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Arm F Phase I and II Starting Dose of Utomilumab: 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Other Names:
  • PF-05082566
  • Anti-CD137

Drug: PF-04518600

Arm B: PF-04518600 0.3 mg/kg by vein every 2 weeks starting Cycle 1 Day 1. Arm C Phase I Starting Dose of PF-04518600: 0.1 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm C Phase II Starting Dose of PF-04518600: Maximum tolerated dose (MTD) from Phase I.

Arm E Phase I and II Starting Dose of PF-04518600 to be determined, given by vein every 2 weeks starting Cycle 1 Day 1.

Arm F Phase I and II Starting Dose of PF-04518600: MTD from Arm C by vein every 2 weeks starting Cycle 1 Day 1.


Experimental: Arm D: Avelumab, Utomilumab, and Radiation

Phase I Starting Dose of Radiation: 60 Gy in 6 Gy / fraction for 10 fractions on days 2-11 of Cycle 1.

Phase II Starting Dose of Radiation: MTD from Phase I.

Phase I and II Starting Dose of Utomilumab: 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Treatment cycles are 28 days.

Drug: Avelumab

Arm A: Avelumab 10 mg/kg by vein every 2 weeks starting Cycle 3 Day 1.

Arm B: Avelumab 10 mg/kg by vein every 2 weeks starting Cycle 3 Day 1.

Arm C Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm D Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm E Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm F Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm G Phase I Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm G Phase II Starting Dose of Avelumab: MTD from Phase I.

Other Name: MSBOO10718C

Drug: Utomilumab

Arm A: Utomilumab 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Arm C Phase I and II Starting Dose of Utomilumab: 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Arm D Phase I and II Starting Dose of Utomilumab: 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Arm F Phase I and II Starting Dose of Utomilumab: 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Other Names:
  • PF-05082566
  • Anti-CD137

Radiation: Radiation

Arm D Phase I Starting Dose of Radiation: 60 Gy in 6 Gy / fraction for 10 fractions on days 2-11 of Cycle 1.

Arm D Phase II Starting Dose of Radiation: MTD from Phase I.

Arm E Phase I Starting Dose of Radiation: 48 Gy in 6 Gy/ fraction for 8 fractions on days 2-11 of Cycle 1.

Arm E Phase II Starting Dose of Radiation: MTD from Phase I.

Arm F Phase I Starting Dose of Radiation: 60 Gy in 6 Gy / fraction for 10 fractions on Days 2-11 of Cycle 1.

Arm F Phase II Starting Dose of Radiation: MTD from Phase I.

Arm G Phase I and II Starting Dose of Radiation: 45 Gy in 1.8 Gy / fraction for 25 fractions on Days 1-5 for the first 5 weeks starting Cycle 1 Day 1.

Other Name: XRT

Experimental: Arm E: Avelumab, PF-04518600, and Radiation

Phase I Starting Dose of Radiation: 60 Gy in 6 Gy / fraction for 10 fractions

Phase II Starting Dose of Radiation: MTD from Phase I.

Phase I and II Starting Dose of PF-04518600 to be determined, given by vein every 2 weeks starting Cycle 1 Day 1.

Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Drug: Avelumab

Arm A: Avelumab 10 mg/kg by vein every 2 weeks starting Cycle 3 Day 1.

Arm B: Avelumab 10 mg/kg by vein every 2 weeks starting Cycle 3 Day 1.

Arm C Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm D Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm E Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm F Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm G Phase I Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm G Phase II Starting Dose of Avelumab: MTD from Phase I.

Other Name: MSBOO10718C

Drug: PF-04518600

Arm B: PF-04518600 0.3 mg/kg by vein every 2 weeks starting Cycle 1 Day 1. Arm C Phase I Starting Dose of PF-04518600: 0.1 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm C Phase II Starting Dose of PF-04518600: Maximum tolerated dose (MTD) from Phase I.

Arm E Phase I and II Starting Dose of PF-04518600 to be determined, given by vein every 2 weeks starting Cycle 1 Day 1.

Arm F Phase I and II Starting Dose of PF-04518600: MTD from Arm C by vein every 2 weeks starting Cycle 1 Day 1.


Radiation: Radiation

Arm D Phase I Starting Dose of Radiation: 60 Gy in 6 Gy / fraction for 10 fractions on days 2-11 of Cycle 1.

Arm D Phase II Starting Dose of Radiation: MTD from Phase I.

Arm E Phase I Starting Dose of Radiation: 48 Gy in 6 Gy/ fraction for 8 fractions on days 2-11 of Cycle 1.

Arm E Phase II Starting Dose of Radiation: MTD from Phase I.

Arm F Phase I Starting Dose of Radiation: 60 Gy in 6 Gy / fraction for 10 fractions on Days 2-11 of Cycle 1.

Arm F Phase II Starting Dose of Radiation: MTD from Phase I.

Arm G Phase I and II Starting Dose of Radiation: 45 Gy in 1.8 Gy / fraction for 25 fractions on Days 1-5 for the first 5 weeks starting Cycle 1 Day 1.

Other Name: XRT

Experimental: Arm F: Avelumab, Utomilumab, PF-04518600, and Radiation

Phase I Starting Dose of Radiation: 60 Gy in 6 Gy / fraction for 10 fractions on Days 2-11 of Cycle 1.

Phase II Starting Dose of Radiation: MTD from Phase I.

Phase I and II Starting Dose of PF-04518600: MTD from Arm C by vein every 2 weeks starting Cycle 1 Day 1.

Phase I and II Starting Dose of Utomilumab: 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Drug: Avelumab

Arm A: Avelumab 10 mg/kg by vein every 2 weeks starting Cycle 3 Day 1.

Arm B: Avelumab 10 mg/kg by vein every 2 weeks starting Cycle 3 Day 1.

Arm C Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm D Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm E Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm F Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm G Phase I Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm G Phase II Starting Dose of Avelumab: MTD from Phase I.

Other Name: MSBOO10718C

Drug: Utomilumab

Arm A: Utomilumab 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Arm C Phase I and II Starting Dose of Utomilumab: 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Arm D Phase I and II Starting Dose of Utomilumab: 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Arm F Phase I and II Starting Dose of Utomilumab: 100 mg by vein every 4 weeks starting Cycle 1 Day 1.

Other Names:
  • PF-05082566
  • Anti-CD137

Drug: PF-04518600

Arm B: PF-04518600 0.3 mg/kg by vein every 2 weeks starting Cycle 1 Day 1. Arm C Phase I Starting Dose of PF-04518600: 0.1 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm C Phase II Starting Dose of PF-04518600: Maximum tolerated dose (MTD) from Phase I.

Arm E Phase I and II Starting Dose of PF-04518600 to be determined, given by vein every 2 weeks starting Cycle 1 Day 1.

Arm F Phase I and II Starting Dose of PF-04518600: MTD from Arm C by vein every 2 weeks starting Cycle 1 Day 1.


Radiation: Radiation

Arm D Phase I Starting Dose of Radiation: 60 Gy in 6 Gy / fraction for 10 fractions on days 2-11 of Cycle 1.

Arm D Phase II Starting Dose of Radiation: MTD from Phase I.

Arm E Phase I Starting Dose of Radiation: 48 Gy in 6 Gy/ fraction for 8 fractions on days 2-11 of Cycle 1.

Arm E Phase II Starting Dose of Radiation: MTD from Phase I.

Arm F Phase I Starting Dose of Radiation: 60 Gy in 6 Gy / fraction for 10 fractions on Days 2-11 of Cycle 1.

Arm F Phase II Starting Dose of Radiation: MTD from Phase I.

Arm G Phase I and II Starting Dose of Radiation: 45 Gy in 1.8 Gy / fraction for 25 fractions on Days 1-5 for the first 5 weeks starting Cycle 1 Day 1.

Other Name: XRT

Experimental: Arm G: Avelumab, Cisplatin, and Radiation

Phase I and II Starting Dose of Radiation: 45 Gy in 1.8 Gy / fraction for 25 fractions on Days 1-5 for the first 5 weeks starting Cycle 1 Day 1.

Phase I and II Starting Dose of Cisplatin: 40 mg/m2 by vein weekly for 6 weeks only.

Phase I Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Phase II Starting Dose of Avelumab: MTD from Phase I.

Drug: Avelumab

Arm A: Avelumab 10 mg/kg by vein every 2 weeks starting Cycle 3 Day 1.

Arm B: Avelumab 10 mg/kg by vein every 2 weeks starting Cycle 3 Day 1.

Arm C Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm D Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm E Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm F Phase I and II Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm G Phase I Starting Dose of Avelumab: 10 mg/kg by vein every 2 weeks starting Cycle 1 Day 1.

Arm G Phase II Starting Dose of Avelumab: MTD from Phase I.

Other Name: MSBOO10718C

Radiation: Radiation

Arm D Phase I Starting Dose of Radiation: 60 Gy in 6 Gy / fraction for 10 fractions on days 2-11 of Cycle 1.

Arm D Phase II Starting Dose of Radiation: MTD from Phase I.

Arm E Phase I Starting Dose of Radiation: 48 Gy in 6 Gy/ fraction for 8 fractions on days 2-11 of Cycle 1.

Arm E Phase II Starting Dose of Radiation: MTD from Phase I.

Arm F Phase I Starting Dose of Radiation: 60 Gy in 6 Gy / fraction for 10 fractions on Days 2-11 of Cycle 1.

Arm F Phase II Starting Dose of Radiation: MTD from Phase I.

Arm G Phase I and II Starting Dose of Radiation: 45 Gy in 1.8 Gy / fraction for 25 fractions on Days 1-5 for the first 5 weeks starting Cycle 1 Day 1.

Other Name: XRT

Drug: Cisplatin
Arm G Phase I and II Starting Dose of Cisplatin: 40 mg/m2 by vein weekly for 6 weeks only.
Other Names:
  • Platinol-AQ
  • Platinol
  • CDDP




Primary Outcome Measures :
  1. Adverse Events of Different Treatment Combinations of Avelumab When Administered in Combination with Checkpoint Agonist(s) with or without Radiation, or Radiation and Cisplatin [ Time Frame: 56 days ]
    Adverse events (AEs) determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

  2. Evaluation of CD8 Immune Biomarkers [ Time Frame: Baseline up to 12 weeks after study drug given ]
    Changes in CD8 expression analyzed before and after treatment using a paired t-test if the data are Normally distributed, and a Wilcoxon signed rank test if not.


Secondary Outcome Measures :
  1. Objective Response Rate per RECIST v1.1 [ Time Frame: Baseline up to 12 weeks after study drug given ]
    Objective response rate determined by radiographic disease assessments per RECIST v1.1.

  2. Objective Response Rate per irRECIST [ Time Frame: Baseline up to 12 weeks after study drug given ]
    Objective response rate determined by radiographic disease assessments per irRECIST.

  3. Progression-Free Survival [ Time Frame: Start of study drugs up to 12 weeks after study drug given ]
    Progression-free survival defined as the time from Cycle 1 start date until the earliest date of disease progression, as determined by investigator assessment of objective radiographic disease assessments per RECIST v1.1 and irRECIST, or death due to any cause, if occurring sooner than progression.

  4. Duration of Response [ Time Frame: Start of study drugs up to 12 weeks after study drug given ]
    Duration of response determined by radiographic disease assessment, defined as the time from earliest date of disease response until the earliest date of disease progression per RECIST v1.1 and irRECIST, or death due to any cause, if occurring sooner than progression.

  5. Overall Survival [ Time Frame: Start of study drugs up to 4 years after study drug given ]
    Overall survival determined from the Cycle 1 start date until death due to any cause.



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.


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

Inclusion Criteria:

  1. For all arms except Arm G, subjects must be refractory to, or intolerant of, established therapy known to provide clinical benefit for their conditions, or where subjects refuse existing therapies. For Arm G, subjects must have newly histologically or cytologically confirmed diagnosis of locally advanced cervical cancer confined to the pelvis only.
  2. Subjects must have measurable disease (RECIST v1.1) or patients may have bone metastatic disease evaluable by Prostate Cancer Working Group 2 (PCWG2) for subjects with metastatic castration-resistant prostate cancer (CRPC) or according to tumor evaluation criteria best suitable and accepted for the tumor type evaluated.
  3. Age >/= 18 years.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  5. Adequate hematologic function defined as: Platelets >/= 100 x 10^9/L; Hemoglobin >/= 9 g/dL; Absolute Neutrophil Count (ANC) >/=1.5 x 10^9/L; White Blood Cell (WBC) >/= 3 x 10^9/L; Absolute Lymphocyte Count (ALC) >/= 0.8 x 10^9/L. Subjects must be transfusion independent (ie, no blood product transfusions for a period of at least 14 days prior to screening).
  6. Adequate liver function defined as: Alanine transaminase (ALT) </= 2.5 x upper normal limit (ULN) (</=5 x ULN for subjects with documented metastatic disease to the liver); Aspartate aminotransferase (AST) </= 2.5 x ULN (</=5 x ULN for subjects with documented metastatic disease to the liver); Alkaline phosphatase < 4 x ULN; Total Bilirubin </= 1.5 x ULN (In the expansion cohort, subjects with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of </= 3 x ULN); Albumin >/=3 g/dL.
  7. Renal function defined serum creatinine </=2 x upper limit of normal (ULN) or estimated creatinine clearance >/=30 ml/min as calculated using the Cockcroft-Gault formula. For Arm G, subjects must have an estimated creatinine clearance >/= 50 ml/min.
  8. Subject has recovered to Grade </= 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03 (NCI-CTCAE v4.03) from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other targeted therapies, with the exception of alopecia. The exceptions for such effects are allowed lab values of </= Grade 2 specified elsewhere in these inclusion criteria.
  9. Life expectancy of at least 12 weeks.
  10. Negative serum pregnancy test in women of childbearing potential within 7 days of first dose of treatment and patients of child-bearing potential must agree to use effective contraception during and after 90 days post dose. A woman of childbearing potential is defined as a premenopausal female capable of becoming pregnant. This includes women on oral, injectable or mechanical contraception; women who are single and women whose male sexual partners have been vasectomized or whose male sexual partners have received or are utilizing mechanical contraceptive devices.
  11. Subjects must have biopsiable disease. For Arms A, B, and C, subjects must have at least two lesions amenable to biopsy and response evaluation. For Arms D, E, F, and G, subjects must have at least three lesions amenable to biopsy, response evaluation, and radiation. Tumor lesions used for biopsy should not be lesions used as RECIST target lesions.
  12. Subjects must give informed consent according to the rules and regulations of the individual participating sites.

Exclusion Criteria:

  1. Subjects with primary central nervous system (CNS) tumor or CNS tumor involvement. However, subjects with metastatic CNS tumors may participate in this study if the subject is: >4 weeks from prior therapy completion (including radiation and/or surgery); Clinically stable with respect to the CNS tumor at the time of study entry; Not receiving steroid therapy in treating CNS tumor or CNS tumor involvement; Not receiving anti-convulsive medications (that were started for brain metastases).
  2. Major surgery, radiation therapy or systemic anti-cancer therapy within 4 weeks of study drug administration (6 weeks for mitomycin C or nitrosoureas). Palliative radiotherapy to a limited field is allowed after consultation with the medical monitor at any time during study participation, including during screening, unless it's clearly indicative of disease progression. For Arm G, subjects who require extended field radiation therapy will be excluded.
  3. Subjects with prior anti-PD-1, anti-PD-L1 treatment. For Arms A and D, subjects may not have had prior 4-1BB treatment. For Arms B and E, subjects may not have had prior OX40 treatment. For Arms C and F, subjects may not have had prior 4-1BB or OX40 treatment.
  4. Diagnosis or recurrence of invasive cancer other than the present cancer within 3 years (except basal or squamous cell carcinoma of the skin that has been definitively treated).
  5. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (>/= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
  6. Active infection requiring systemic therapy.
  7. Treatment with an investigational anti-cancer study drug within 4 weeks prior to study drug administration date.
  8. Concurrent therapy with approved or investigational anticancer therapeutics.
  9. Known prior severe hypersensitivity to investigational product(s) or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade >/= 3).
  10. If in Arm G, significant allergic reaction to cisplatin.
  11. Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses </= 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  12. Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
  13. Prior organ transplantation including allogenic stem-cell transplantation.
  14. Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
  15. 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 positive).
  16. Vaccination (live attenuated virus) within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines.
  17. Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however, alopecia, sensory neuropathy Grade </= 2, or other Grade </= 2 not constituting a safety risk based on investigator's judgment are acceptable.
  18. Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  19. Medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
  20. Pregnancy or lactation.
  21. Men whose partner is a woman of child-bearing potential, (i.e. biologically able to conceive), and who is not employing two forms of highly effective contraception. Highly effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used by both sexes during the study and must be continued for 90 days after the end of study treatment. Women of child-bearing potential is defined as sexually mature women who are not surgically sterile or who have not been naturally postmenopausal for at least 12 consecutive months (e.g., who has had menses any time in the preceding 12 consecutive months).
  22. A diagnosis of active scleroderma, lupus, or other rheumatologic disease which in the opinion of the treating radiation oncologist precludes safe radiation therapy.
  23. Has had prior radiation therapy within the past 3 months where the high dose area of the prior radiation would overlap with the high dose area of the intended radiation based on the judgement of the treatment oncologist.
  24. For Arm G, patients with disease beyond the pelvis, including but not limited to the para-aortic nodes as determined by PET/CT will be excluded.

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): NCT03217747


Contacts
Contact: Aung Naing, MD 713-563-1930 CR_Study_Registration@mdanderson.org

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Clinical Research Operations       CR_Study_Registration@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
Pfizer
Investigators
Principal Investigator: Aung Naing, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03217747     History of Changes
Other Study ID Numbers: 2017-0014
First Posted: July 14, 2017    Key Record Dates
Last Update Posted: May 1, 2018
Last Verified: April 2018

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

Keywords provided by M.D. Anderson Cancer Center:
PF-04518600
Metastatic solid tumors
Advanced solid tumors
Avelumab
MSBOO10718C
Utomilumab
PF-05082566
Anti-CD137
Cisplatin
Platinol-AQ
Platinol
CDDP
Radiation Therapy
XRT

Additional relevant MeSH terms:
Neoplasms
Breast Neoplasms
Genital Neoplasms, Female
Urologic Neoplasms
Genital Neoplasms, Male
Lip Neoplasms
Bone Neoplasms
Thyroid Neoplasms
Eye Neoplasms
Cartilage Diseases
Soft Tissue Neoplasms
Neoplasms, Fibrous Tissue
Neoplasms by Site
Breast Diseases
Skin Diseases
Urogenital Neoplasms
Genital Diseases, Male
Mouth Neoplasms
Head and Neck Neoplasms
Lip Diseases
Mouth Diseases
Stomatognathic Diseases
Bone Diseases
Musculoskeletal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Thyroid Diseases
Eye Diseases
Connective Tissue Diseases
Neoplasms, Connective Tissue