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PTC-596 in Women With Ovarian Cancer Receiving Neoadjuvant Chemotherapy

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ClinicalTrials.gov Identifier: NCT03206645
Recruitment Status : Recruiting
First Posted : July 2, 2017
Last Update Posted : September 26, 2017
Sponsor:
Collaborator:
PTC Therapeutics
Information provided by (Responsible Party):
University of Oklahoma

Brief Summary:
This is an open-label Phase Ib dose-escalation study to assess MTD, safety, tolerability, and PK of PTC596 when combined with standard paclitaxel and carboplatin for women with stage III or IV epithelial ovarian, primary peritoneal or fallopian tube cancer receiving neoadjuvant chemotherapy. For all cohorts, PTC596 will be given in combination with paclitaxel and carboplatin.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: PTC596 Phase 1

Detailed Description:
For all cohorts, PTC596 will be orally administered at least 30 minutes prior to IV chemotherapy, twice a week on day 1, 4, 8, 11, 15, 18 of each 21-day cycle. The starting dose is 1.3 mg/kg in cohort 1. Carboplatin (AUC = 6 mg/mL min) will be administered IV on day 1 and paclitaxel (80 mg/m2) will be administered IV once a week on days 1, 8 and 15 of each 21-day cycle. Dose escalation levels for PTC- 596 are1.3mg/kg, 2.6mg/kg, 5.2 mg/kg and 7.0mg/kg Q BIW. Doses may be de-escalated for management of toxicity with the lowest dose being 0.65 mg/kg. A total of 3 cycles of PTC596 and paclitaxel/ carboplatin will be given before iCRS and an additional 3-5 cycles following iCRS.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Intervention Model: Single Group Assignment
Intervention Model Description: This trial will utilize a traditional 3+ 3 design with dose escalation.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase IB Study of Weekly Paclitaxel + Carboplatin With the BMI-1 Inhibitor PTC596 in Women With Stage III or IV Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancer Receiving Neoadjuvant Chemotherapy
Actual Study Start Date : August 15, 2017
Estimated Primary Completion Date : June 1, 2019
Estimated Study Completion Date : June 1, 2022


Arm Intervention/treatment
Experimental: Carboplatin/Paclitaxel + PTC
Carboplatin AUC 6mg/L IV on day 1; Paclitaxel 80mg/m2 IV on day 1, 8, 15; PTC596 (1.3 mg/kg in cohort 1), PO, twice a week, on day 1, 4, 8, 11, 15 and 18 per 21-day cycle for the first 3 cycles.
Drug: PTC596
PTC596 will be given in combination with carboplatin and paclitaxel for up to 5 cycles depending on which cohort the patient is in.




Primary Outcome Measures :
  1. Maximum tolerated dose and dose limiting toxicities [ Time Frame: 3 years ]
    To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of PTC596 in combination with and following conventional chemotherapy and as maintenance. 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).

  2. Number of patients able to tolerate drug combination [ Time Frame: 3 years ]
    To examine the tolerability of the combination at the MTD of PTC596 assessed in combination with standard neoadjuvant chemotherapy.

  3. Phase 2 Dose [ Time Frame: 3 years ]
    To determine the recommended phase II dose (RP2D) of PTC596 in combination with standard neoadjuvant chemotherapy.


Secondary Outcome Measures :
  1. Measure CA-125 to evaluate clinical response [ Time Frame: 3 years ]
  2. Evaluate pharmacokinetic Area Under the Curve (AUC) [ Time Frame: 3 months ]
    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

  3. Evaluate pharmacokinetic Maximum Concentration observed (Cmax) [ Time Frame: 3 months ]
    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

  4. Evaluate pharmacokinetic Time of Maximum Concentration observed (Tmax) [ Time Frame: 3 months ]
    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

  5. Evaluate pharmacokinetic half life (t1/2) [ Time Frame: 3 months ]
    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



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   There are only women in this patient population.
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically documented epithelial ovarian, primary peritoneal or fallopian tube carcinoma or high grade serous adenocarcinoma, endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, or adenocarcinoma not otherwise specified (N.O.S.).
  • Newly diagnosed and be previously untreated. Adequate bone marrow function, renal function and hepatic function. Neuropathy (sensory and motor) less than or equal to Grade 1.
  • No active infection requiring parenteral antibiotics or a serious uncontrolled medical illness or disorder within four weeks of study entry.
  • Hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration. Continuation of hormone replacement therapy is permitted.
  • 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.

Exclusion Criteria:

  • Prior treatment with PTC596 or standard of care drugs (cis- or carboplatin or paclitaxel.
  • Use of an investigational drug within 4 weeks of dosing in the current study.
  • 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.
  • 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.
  • Presence or history of moderate to severe pulmonary dysfunction.

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): NCT03206645


Contacts
Contact: Ingrid Block, RN 405 271-8777 ingrid-block@ouhsc.edu

Locations
United States, Oklahoma
University of Oklahoma Health Sciences Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Kathleen Moore, MD         
Sponsors and Collaborators
University of Oklahoma
PTC Therapeutics
Investigators
Study Chair: Kathleen Moore, MD University of Oklahoma

Responsible Party: University of Oklahoma
ClinicalTrials.gov Identifier: NCT03206645     History of Changes
Other Study ID Numbers: 8023
First Posted: July 2, 2017    Key Record Dates
Last Update Posted: September 26, 2017
Last Verified: September 2017

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

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action