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Brief Title: A Dose Escalation and Confirmation Study of PT-112 in Advanced Solid Tumors in Combination With Avelumab

A Phase 1b/2a Dose Escalation and Confirmation Study of PT-112 in Advanced Solid Tumors in Combination With Avelumab

INTRODUCTION

  • Org Study ID: PT-112-103-PAVE-1
  • Secondary ID: N/A
  • NTC ID: NCT03409458
  • Sponsor: 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.

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.


  • Overall Status
    Recruiting
  • Start Date
    April 24, 2018
  • Phase
    Phase 1/Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Recommended dose (RD) of PT-112 to be used in combination with avelumab for further studies in patients with advanced solid tumors.

Primary Outcome 1 - Timeframe: 24 months

CONDITION

  • 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)

ELIGIBILITY


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;

Gender: All

Minimum Age: N/A

Maximum Age: 18 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Daniel D Karp, MD

Role: Principal Investigator

Affiliation: M.D. Anderson Cancer Center

Overall Contact

Name: Daniel D Karp, MD

Phone: (919) 867-1616

Email: dhudson@clinipace.com

LOCATION

Facility Status Contact
Facility: Mayo Clinic
Phoenix, Arizona 85054
United States 		Status: Recruiting Contact:
TBD TBD
Facility: University of Colorado Cancer Center
Aurora, Colorado 80045
United States 		Status: Recruiting Contact: N/A
Facility: Mayo Clinic
Jacksonville, Florida 32224
United States 		Status: Recruiting Contact: N/A
Facility: Mayo Clinic
Rochester, Minnesota 55905
United States 		Status: Recruiting Contact: N/A
Facility: University of Texas MD Anderson Cancer Center
Houston, Texas 77030
United States 		Status: Recruiting Contact:
TBD TBD

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