Description:
This is a Phase 1/2, open-label, multi-center, non-randomized, dose-escalation study to be
conducted in two parts: the Dose Escalation Phase and the Dose Expansion Phase. The Dose
Escalation Phase will determine the Maximum Tolerated Dose (MTD) and recommended Phase 2
dose(s) (RP2D) of PT-112 Injection and evaluate its safety and tolerability, and PK
(pharmacokinetics).
The Dose Escalation Phase and is no longer enrolling. The Dose Expansion Phase currently has
two cohorts: one for the study of PT-112 in patients with thymoma and thymic carcinoma, and
the second in the study of PT-112 in metastatic castrate-resistant prostate cancer (mCRPC).
Condition or disease: Advanced Solid Tumors; Thymoma and Thymic Carcinoma; Metastatic
Castrate Resistant Prostate Cancer (mCRPC) Intervention/treatment: Drug: PT-112 Injection
Phase: Phase 1/2
Title
- Brief Title: A Phase 1 Study of PT-112 Injection in Subjects With Advanced Solid Tumors
- Official Title: A Phase 1, Open-Label, Dose-Escalation Study Evaluating the Safety, Pharmacokinetics, and Clinical Effects of Intravenously Administered PT-112 Injection in Subjects With Advanced Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
PT-112-101
- NCT ID:
NCT02266745
Conditions
Interventions
Drug | Synonyms | Arms |
---|
PT-112 Injection | PT-112 | PT-112 injection |
Purpose
This is a Phase I, open-label, multi-center, non-randomized, dose-escalation study to be
conducted in two parts: the Dose Escalation Phase and the Dose Confirmation Phase. The Dose
Escalation Phase will determine the Maximum Tolerated Dose (MTD) and recommended Phase 2
dose(s) (RP2D) of PT-112 Injection and evaluate its safety and tolerability, PK
(pharmacokinetic) and preliminary clinical effects. The Dose Confirmation Phase will be a
cohort expansion at or below the MTD of PT-112 Injection. Subjects who tolerate the drug and
who do not experience progressive disease may continue to receive PT-112 Injection at the
discretion of the Principal Investigator for up to 6 cycles. For subjects who tolerate
PT-112 Injection and who experience an objective response or stable disease through 6
cycles, the Sponsor will continue to provide PT-112 Injection under a separate mechanism,
e.g., an extension protocol.
Detailed Description
This is a Phase I, open-label, multi-center, non-randomized, dose-escalation study to be
conducted in two parts: the Dose Escalation Phase and the Dose Confirmation Phase. The Dose
Escalation Phase will determine the Maximum Tolerated Dose (MTD) and recommended Phase 2
dose(s) (RP2D) of PT-112 Injection and evaluate its safety and tolerability, PK
(pharmacokinetic) and preliminary clinical effects. The Dose Confirmation Phase will be a
cohort expansion at or below the MTD of PT-112 Injection. Subjects who tolerate the drug and
who do not experience progressive disease may continue to receive PT-112 Injection at the
discretion of the Principal Investigator for up to 6 cycles. For subjects who tolerate
PT-112 Injection and who experience an objective response or stable disease through 6
cycles, the Sponsor will continue to provide PT-112 Injection under a separate mechanism,
e.g., an extension protocol.
Trial Arms
Name | Type | Description | Interventions |
---|
PT-112 injection | Experimental | PT-112 Injection, administered by intravenous infusion | |
Eligibility Criteria
Key Inclusion Criteria:
- Pathologically confirmed advanced solid tumor for which standard therapy proven to
provide clinical benefit does not exist or is no longer effective.
- Eastern Collaborative Oncology Group (ECOG) Performance Status of 0-1 (Appendix 1).
- Evaluable disease, either measurable on physical examination or imaging by Response
Evaluation Criteria in Solid Tumors (RECIST v1.1, Appendix 2), or by informative
tumor marker(s).
- Laboratory values at the Screening Visit:
1. Absolute neutrophil count (ANC) ≥1,500/mm3;
2. Platelets ≥100,000/mm3;
3. Total bilirubin ≤1.5 × the upper limit of normal (ULN) (subjects with Gilbert's
Syndrome are allowed if direct bilirubin is within normal limits);
4. Aspartate aminotransferase (AST [SGOT]) ≤2.5 × the ULN;
5. Alanine aminotransferase (ALT [SGPT]) ≤2.5 × the ULN;
6. Serum albumin ≥3.0 gm/dL;
7. Serum creatinine ≤1.5 mg/dL or a measured creatinine clearance ≥60 mL/min; and
Negative serum β hCG (human chorionic gonadotropin) test in women of
childbearing potential (defined as women ≤50 years of age, or >50 years of age
with a history of amenorrhea for ≤12 months prior to study entry).
- Subjects with primary liver cancer or hepatic metastasis are eligible to enroll,
provided that, at the Screening Visit, the following criteria are met:
1. Total bilirubin is no higher than the ULN;
2. AST and ALT are each ≤5 × the ULN;
3. Severe liver dysfunction (Child-Pugh Class B or C) is not present; and
4. Subjects with a history of esophageal bleeding have varices that have been
sclerosed or banded and no bleeding episodes have occurred during the prior 6
months.
- If there is a known history of brain metastases, either treated with radiation
therapy or untreated, the metastatic disease must be stable in the judgment of the
Principal Investigator and must not require ongoing treatment with corticosteroids or
anticonvulsants.
- Willing and able to provide written Informed Consent and comply with the requirements
of the study.
Key Exclusion Criteria:
- Any cytotoxic chemotherapy within 21 days prior to initiation of study drug.
- Any immunomodulatory drug therapy, anti-neoplastic hormonal therapy (unless dose has
been stable for 3 months prior to Baseline and will remain stable during the trial),
immunosuppressive therapy, corticosteroids >20 mg/day prednisone or equivalent, or
growth factor treatment (e.g., erythropoietin) within 14 days prior to initiation of
study drug.
- Presence of an acute or chronic toxicity of prior chemotherapy, with the exception of
alopecia, that has not resolved to ≤Grade 1, as determined by National Cancer
Institute Common Toxicity Criteria for Adverse Effects (CTCAE) v 4.0
(http://evs.nci.nih.gov/ftp1/CTCAE/About.html).
- Receipt of more than 3 prior regimens of cytotoxic chemotherapy for metastatic
disease unless prior approval is granted by the Sponsor.
- Bone marrow reserve which, in the clinical judgment of the Principal Investigator, is
not adequate for participation in this trial.
- Radiotherapy within 28 days prior to baseline.
- Receipt of radiotherapy to >25 % of bone marrow.
- Major surgery within 28 days prior to initiation of study drug.
- Life expectancy <12 weeks.
- Active bacterial, viral, or fungal infection requiring systemic therapy.
- Known human immunodeficiency virus or acquired immunodeficiency syndrome related
illness.
- Clinically significant hearing impairment, as judged by the Principal Investigator.
- Uncontrolled congestive heart failure (New York Heart Association Classification 3 or
4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral
artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within
3 months prior to initiation of study drug.
- Unstable cardiac dysrhythmias or persistent prolongation of the corrected QT interval
(QTc) (Fridericia) to >450 msec for males or >470 msec for females.
- Previous malignancy, except for non-squamous-cell carcinoma of skin or carcinoma
in-situ of the uterine cervix, unless the tumor was treated with curative intent more
than 2 years prior to study entry.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Determine the safety and tolerability, Dose Limiting Toxicity(ies) (DLT), Maximum Tolerated Dose (MTD), and recommended Phase 2 dose(s) (RP2D) |
Time Frame: | 28-day cycle |
Safety Issue: | |
Description: | The primary endpoint is to determine the safety profile and MTD of PT-112 Injection. Assessments will include drug exposure; characterization of DLTs; characterization of the type, incidence, severity, seriousness, and relationship to treatment of adverse events (AEs), and effects on vital signs and laboratory parameters. |
Secondary Outcome Measures
Measure: | Document any observed anti-tumor effects |
Time Frame: | Day 1, Day 56 and every 56 days subsequently |
Safety Issue: | |
Description: | Subjects will be assessed for clinical activity of PT-112 Injection every 2 cycles by appropriate physical examination or computed tomography imaging techniques, using RECIST v1.1; and, where appropriate, informative tumor markers every cycle. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Phosplatin Therapeutics |
Last Updated
November 9, 2016