Study of Oral PQR309 in Patients With Advanced Solid Tumors

NCT02483858 | Completed Phase 1 FDA Drug

• 1 other identifier: PQR309-003
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, multi-center, non-randomized, dose escalation Phase 1 study evaluating safety, tolerability, PK (pharmacokinetics) and efficacy of PQR309 in the treatment of selected patients with advanced solid tumors.

Conditions

Cancer

Keywords

oncology, solid tumors

Outcome Measures

Primary Outcomes (2)

• To identify the Maximum Tolerated Dose (MTD) of PQR309 administered in different (continuous and intermittent) dosing schedules. To evaluate efficacy of PQR309 in selected patient population: • Solid tumors with PI3K/mTOR activation • Human Papilloma

  MTD based on the rate of dose-limiting toxicities. The MTD is defined as the maximum dose level at which ≤ 1/6 patients have dose limiting toxicities (DLTs).

  In average 1 year

• Objective response rate (ORR) according to the response evaluation• Solid tumors with PI3K/mTOR activation • Human Papilloma Virus (HPV) positive Head and neck squamous cell carcinoma (HNSCC) containing activating PIK3CA mutations

  Expansion part criteria in solid tumors (RECIST), version 1.1

  in average 2 years

Secondary Outcomes (60)

• Number of patients with adverse Events and serious adverse events

  Cycle1 on Day1,8,15, Cycle 2 and subsequent cycles on Day 1, End of the treatment up to 3 days and as follow up 30 days after last dosing

• Number of patients with adverse Events and serious adverse events

  Assessment on Day 1 after basline, Cycle1 on Day 8,15, Cycle 2 and subsequent cycles on Day 1, End of the treatment up to 3 days and as follow up 30 days after last dosing

• Physical examination according to ECOG (Eastern Cooperative Oncology Group) Performance Status

  Cycle 1 on Day 8,15, Cycle 2 and subsequent cycles on Day1 , end of treatment up to 3 days after

• Physical examination according to ECOG (Eastern Cooperative Oncology Group) Performance Status

  Cycle 1 on Day 1,8,15, Cycle 2 and subsequent cycles on Day1 , end of treatment up to 3 days after

• Physical examination according to ECOG (Eastern Cooperative Oncology Group) Performance Status

  Assessment on Day1,2, Cycle 1 on Day 4,8,9,15

Study Arms (1)

PQR309

EXPERIMENTAL

Different dose Evaluation (continous and intermittent) 20-160mg daily

Drug: PQR 309

Interventions

PQR 309 DRUG

Intervention of this drug may include safety, tolerability, PK (pharmacokinetics) and efficacy

Also known as: PI3K/mTOR/AKT Inhibitor

PQR309

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥ 18 years of age.
• Histologically or cytologically confirmed diagnosis of solid malignancy, for which no standard curative or life prolonging therapy is available.
• Have an ECOG Performance Status of ≤ 1. Refer to Appendix 1.
• Life expectancy of ≥ 12 weeks.
• Adequate bone marrow, liver, and renal functions, defined as:
• Platelet count ≥ 100 x 109/L, absolute neutrophil count (ANC)
• ≥ 1.5 x 109/L, Hemoglobin ≥ 9 g/dL.
• ALT and AST ≤ 2.5 upper limit normal (ULN), or \< 5 x ULN if liver metastases are present; serum total bilirubin ≤ ULN or 1.5 x ULN if liver metastases are present or total 3 x ULN with direct bilirubin ≤ ULN in patients with well documented Gilbert Syndrome.
• Serum Creatinine \< 1.5 x ULN (upper limit of normal) or estimated creatinine clearance ≥ 60 mL/min, as calculated using method standard for the institution (Appendix 2).
• Glycated hemoglobin (HgbA1c) ≤ 7 %; Fasting Plasma Glucose (FPG) ≤ 7.0 mmol/L (125 mg/dL).
• Women of childbearing potential must have a negative pregnancy test (urine or serum) performed within 7 days prior to the start of study drug.
• Able and willing to swallow and retain oral medication.
• Subject or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.
• Expansion part:
• Patients must have known PI3K/mTOR pathway gene aberrations (from molecular profiling studies).

You may not qualify if:

• Concurrent or previous anti-cancer chemotherapy, immunotherapy or investigational agents \< 3 weeks, or palliative radiation \< 2 weeks prior to the first day of study treatment. Patients who receive gamma knife radiosurgery for brain metastases or whole brain radiation are eligible if gamma knife radiosurgery was performed \> 2 weeks before treatment is started or whole brain radiation was performed \> 4 weeks before treatment is started, and are clinically stable.
• Hormonal anticancer therapies except for LHRH antagonists or LHRH agonists in hormone-refractory prostate cancer
• Patient has a known hypersensitivity to any of the excipients of PQR309.
• Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects.
• Patients with poorly controlled diabetes mellitus, steroid-induced diabetes mellitus, HbA1c \> 7%, or FPG \> 7.0 mmol/L (125 mg/dL).
• Patients who are on (or will require) prolonged systemic corticosteroid treatment during the study, except for:
• if receiving corticosteroids, patients must have been on a stable or decreasing dose of corticosteroids and no more than 1 mg of dexamethasone a day or equivalent, i.e. 6 mg prednisone or 25 mg hydrocortisone for at least 5 days prior to date of enrollment.
• a short duration (\< 5 days) of systemic corticosteroids e.g., of chronic obstructive pulmonary disease, or as an antiemetic corresponding at maximum to the anti-inflammatory potency of 4 mg dexamethasone for treatment;
• topical applications for treatment of e.g., rash, inhaled sprays for treatment of e.g., obstructive airways diseases, eye drops or local Protocol No. PQR309-003 Protocol Amendment 3, 23 September 2015 PIQUR Therapeutics AG - Confidential Page 15 of 108 injections (e.g., intra-articular);
• Patients who have taken herbal medications and certain fruits within 7 days prior to starting study drug, see section 11.1.2.7.
• Patients who have other concurrent severe and/or uncontrolled medical conditions that would, in the investigator's judgment, contraindicate patient participation in the clinical study (e.g., active or uncontrolled severe infection, chronic active hepatitis, immuno-compromised, acute or chronic pancreatitis, uncontrolled high blood pressure, interstitial lung disease, etc.).
• Patient has a known history of HIV infection (testing not mandatory).
• Patient has any of the following cardiac abnormalities:
• History of, or current, documented congestive heart failure (New York Heart Association functional classification III - IV), documented cardiomyopathy.
• Left Ventricular Ejection Fraction (LVEF) \< 40% as determined by Multiple Gated Acquisition (MUGA) scan or echocardiogram (ECHO).

Sponsors & Collaborators

• PIQUR Therapeutics AG: lead
• Roswell Park Cancer Institute: collaborator
• M.D. Anderson Cancer Center: collaborator
• Mayo Clinic: collaborator
• Hospital Clinic of Barcelona: collaborator
• University College London Hospitals: collaborator
• Churchill Hospital: collaborator
• Case Western Reserve University: collaborator
• University Hospital, Zürich: collaborator

Study Sites (1)

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Neoplasms

Study Officials

• Mateusz Opyrchal

  Roswell Park Cancer Institute

  STUDY DIRECTOR

• Filip Janku

  MD Anderson Cancer

  PRINCIPAL INVESTIGATOR

• Afshin Dowlati

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

• Alex Adjei

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Jordi Rodon

  Vall d'Hebron University Hospital

  PRINCIPAL INVESTIGATOR

• Martin Forster

  University College London Hospitals

  PRINCIPAL INVESTIGATOR

• Sarah Bladgen

  Chruchill Hospital

  PRINCIPAL INVESTIGATOR

• Andreas Wicki

  Basel University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2015
• First Posted: June 29, 2015
• Study Start: March 21, 2019
• Primary Completion: March 21, 2019
• Study Completion: March 21, 2019
• Last Updated: March 22, 2019

Record last verified: 2019-03

Locations

US (1)