Description:
This is an open-label Phase Ib dose-escalation study to determine the safety, tolerability,
and pharmacokinetics of PTC-596 when combined with and following conventional chemotherapy
and as maintenance therapy as a capsule (weight based dosing) and a tablet (fixed dosing) in
women with epithelial ovarian, fallopian tube or primary peritoneal cancer which is
previously untreated.
Title
- Brief Title: PTC-596 in Women With Ovarian Cancer Receiving Neoadjuvant Chemotherapy
- Official Title: Phase 1B Trial With PTC-596 in High-Grade Serous Ovarian Cancer: a Targeted Approach Toward Chemoresistant Stem-Like Cancer Cells
Clinical Trial IDs
- ORG STUDY ID:
PTC-001
- NCT ID:
NCT03206645
Conditions
Interventions
Drug | Synonyms | Arms |
---|
PTC596 | | Carboplatin/Paclitaxel + PTC596 |
Purpose
This is an open-label Phase Ib dose-escalation study to determine the safety, tolerability,
and pharmacokinetics of PTC-596 when combined with and following conventional chemotherapy
and as maintenance therapy as a capsule (weight based dosing) and a tablet (fixed dosing) in
women with epithelial ovarian, fallopian tube or primary peritoneal cancer which is
previously untreated.
Detailed Description
For all cohorts, the study drug PTC-596 will be orally administered prior to chemotherapy
(paclitaxel and carboplatin), twice a week of each 21-day cycle. Chemotherapy will be
administered on day 1 of each cycle by vein. Dose escalation levels for PTC-596 will occur
per protocol and doses may be de-escalated for management of toxicity. Patients will receive
a total of 3 cycles of PTC-596 and chemotherapy. Surgery will be performed within 6 weeks
after the last dose of Cycle 3. An additional 3-7 cycles of PTC-596 and chemotherapy
(carboplatin and paclitaxel) may be given as maintenance therapy for up to two years at the
discretion of the treating physician.
Trial Arms
Name | Type | Description | Interventions |
---|
Carboplatin/Paclitaxel + PTC596 | Experimental | Carboplatin AUC 6mg/L IV on day 1; Paclitaxel 175mg/m2 IV on day 1; PTC596 PO, twice a week, on day 1, 4, 8, 11, 15 and 18 per 21-day cycle for the first 3 cycles. | |
Eligibility Criteria
Inclusion Criteria:
- Patients must have histologic diagnosis of epithelial ovarian, fallopian tube, or
primary peritoneal carcinoma per pre-treatment biopsies by laparoscopy, or
interventional radiology or CT guided core biopsy.
- Patients with the following histologic epithelial cell types are eligible: High grade
serous adenocarcinoma, endometrioid adenocarcinoma, undifferentiated carcinoma, clear
cell adenocarcinoma, mixed epithelial carcinoma, or adenocarcinoma not otherwise
specified (N.O.S.).
- Adequate bone marrow function, renal function, hepatic function, and neurologic
function per protocol.
- Patients should be free of active infection requiring parenteral antibiotics or a
serious uncontrolled medical illness or disorder within four weeks of study entry.
- Any hormonal therapy directed at the malignant tumor must be discontinued at least one
week prior to registration. Continuation of hormone replacement therapy is permitted.
- Patients must have a performance status score of 0, 1, or 2 by Eastern Cooperative
Group (ECOG) criteria.
- Patients of childbearing potential must have a negative pregnancy test prior to the
study entry and be practicing an effective form of contraception. If applicable,
patients must discontinue breastfeeding prior to study entry.
- Patients must have satisfactory results for the baseline laboratory analyses and
diagnostic procedures as specified in the protocol.
- Patients must have pre-treatment tumor tissue available or agree for tissue collection
from IR guided biopsy.
- Life expectancy of at least 3 months
Exclusion Criteria:
- Prior treatment with PTC596 or standard of care drugs (cis- or carboplatin or
paclitaxel.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to PTC596 or other agents used in this study.
- Have a clinical requirement for ongoing systemic immunosuppressive therapy such as
chronic steroid use not related to chemotherapy administration.
- Receiving treatment for active autoimmune disease.
- History of other invasive malignancies, with the exception of non-melanoma skin cancer
and other specific malignancies within the last three years.
- Prior radiotherapy to any portion of the abdominal cavity or pelvis.
- Prior chemotherapy for any abdominal or pelvic tumor.
- Known active hepatitis, ongoing systemic bacterial, fungal, or viral infection; known
human immunodeficiency virus (HIV) infection or acquired-immunodeficiency syndrome
(AIDS)-related illness.
- Have concurrent severe medical problems unrelated to the malignancy that would
significantly limit full compliance with the study.
- Have childbearing potential but not practicing adequate contraception.
- History or active CNS disease.
- Concomitant therapy with any of the following: other non-study cytotoxic chemotherapy;
other investigational therapies.
- Prior bone marrow/hematopoietic stem cell transplantation
- History of solid organ, bone marrow, or progenitor cell transplantation
- History of major surgical procedure within 28 days prior to start of study treatment
- Presence or history of moderate to severe pulmonary dysfunction.
- Use of an investigational drug within 4 weeks of dosing in the current study
Maximum Eligible Age: | 99 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Female |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Maximum tolerated dose and dose limiting toxicities |
Time Frame: | 42 days |
Safety Issue: | |
Description: | To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of PTC596 in combination with and following conventional chemotherapy and as maintenance as a capsule (weight-based dosing) and a tablet (fixed dosing). Standard chemotherapy will be comprised of carboplatin and weekly paclitaxel. The DLTs will be based on adverse events that occur during administration of the first 2 cycles of combination PTC596 and chemotherapy (a cycle = 21 days). |
Secondary Outcome Measures
Measure: | Evaluate clinical response |
Time Frame: | 3 years |
Safety Issue: | |
Description: | Evaluate clinical response by measuring serum CA-125. If CA-125 is initially above the upper normal limit, it must normalize for patients to be considered in complete clinical response. |
Measure: | Evaluate pharmacokinetic Area Under the Curve (AUC) |
Time Frame: | 3 months |
Safety Issue: | |
Description: | To evaluate pharmacokinetic parameters of PTC596 in patients with stage III or IV epithelial ovarian, primary peritoneal or fallopian tube cancer receiving neoadjuvant chemotherapy with carboplatin/paclitaxel |
Measure: | Evaluate pharmacokinetic Maximum Concentration observed (Cmax) |
Time Frame: | 3 months |
Safety Issue: | |
Description: | To evaluate pharmacokinetic parameters of PTC596 in patients with stage III or IV epithelial ovarian, primary peritoneal or fallopian tube cancer receiving neoadjuvant chemotherapy with carboplatin/paclitaxel |
Measure: | Evaluate pharmacokinetic Time of Maximum Concentration observed (Tmax) |
Time Frame: | 3 months |
Safety Issue: | |
Description: | To evaluate pharmacokinetic parameters of PTC596 in patients with stage III or IV epithelial ovarian, primary peritoneal or fallopian tube cancer receiving neoadjuvant chemotherapy with carboplatin/paclitaxel |
Measure: | Evaluate pharmacokinetic half life (t1/2) |
Time Frame: | 3 months |
Safety Issue: | |
Description: | To evaluate pharmacokinetic parameters of PTC596 in patients with stage III or IV epithelial ovarian, primary peritoneal or fallopian tube cancer receiving neoadjuvant chemotherapy with carboplatin/paclitaxel |
Measure: | Progression free survival |
Time Frame: | one year |
Safety Issue: | |
Description: | The duration of time (one year) that patients are alive and their cancer is progression-free. |
Measure: | Progression free survival |
Time Frame: | two years |
Safety Issue: | |
Description: | The duration of time (two years) that patients are alive and their cancer is progression-free. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | University of Oklahoma |
Last Updated
November 21, 2019