Vinorelbine in Relapsed Platinum Resistant or Refractory C5 High Grade Serous, Endometrioid, or Undifferentiated Primary Peritoneum, Fallopian Tube or Ovarian Cancer

Brief Title

Vinorelbine in Relapsed Platinum Resistant or Refractory C5 High Grade Serous, Endometrioid, or Undifferentiated Primary Peritoneum, Fallopian Tube or Ovarian Cancer

Official Title

Phase II Study of Intravenous Vinorelbine in Patients With Relapsed Platinum Resistant or Refractory C5 High Grade Serous, Endometrioid, or Undifferentiated Primary Peritoneum, Fallopian Tube or Ovarian Cancer (VIP)

Brief Summary

      This is a phase II study in patients with recurrent platinum resistant or refractory C5
      high-grade serous, endometrioid or undifferentiated ovarian, primary peritoneal or fallopian
      tube cancer. All patients with high-grade serous, endometrioid or undifferentiated primary
      peritoneum, fallopian tube or ovarian cancer will be eligible to be screened for this trial
      and will be required to sign a pre-screening consent form.
    

Detailed Description

      Background Therapeutic Information In ovarian cancer, several single agent phase II trials of
      vinorelbine in recurrent OC have shown variable response rates of 3 - 30%. However, previous
      studies have involved "all-comers" and no reported trials have selected patients based on
      confirmed pure HGSOC or a biomarker of relevance. Preclinical studies suggest that genes
      involved in microtubule dynamics, are significantly over-expressed in C5 tumours.
      Importantly, increased sensitivity was demonstrated of C5-like cell lines to tubulin
      depolymerising agents like vincristine and vinorelbine compared with microtubule stabilizing
      agents like paclitaxel. Subsequent studies on patient derived xenograft (PDX) models of C5
      HGSOC (including platinum resistant models) showed responses for more than 50 days when
      treated with vinorelbine, providing preclinical proof that vinorelbine may be an effective
      therapeutic option in targeting the C5 subclass of HGSOC, including in platinum resistant or
      refractory disease.

      Risk/ Benefit of Intervention Vinorelbine is a hemisynthetic vinca alkaloid that is
      traditionally administered intravenously via an infusion. The mechanism of action is
      disruption of microtubules by their reversible binding to tubulin resulting in mitotic
      spindle dissolution and metaphase arrest in dividing cells. This trial will afford patients
      with C5 relapsed platinum resistant or refractory HGSOC additional treatment options that may
      potentially have greater benefit than standard chemotherapy.

      Tolerability The main dose limiting toxicity associated with IV vinorelbine in lung cancer is
      myelosuppression with Grade 3-4 neutropenia seen in up to 46% of patients. However, the
      febrile neutropenia rate was low at <5%. Mild to moderate gastrointestinal toxicity was
      observed with nausea and vomiting being the most common adverse effect. Grade 3/4 nausea or
      vomiting occurred in 7% - 17% of patients and primary prophylaxis is recommended.
      Neurotoxicity was also reported with the use of vinorelbine. Peripheral neuropathy was
      observed in up to 11% of patients,and neuroconstipation was documented to affect up to 24% of
      patients, however most of these cases were mild, grade 1-2. A similar toxicity profile was
      observed in patients with platinum resistant ovarian cancer treated with vinorelbine.
      Leukopenia was the most common dose limiting toxicity followed by anemia, fatigue and nausea.

      Aim and Objectives of the trial The purpose of this trial is to determine if targeting
      platinum resistant or refractory C5 high-grade serous, high grade endometrioid or
      undifferentiated ovarian, primary peritoneal and fallopian tube with vinorelbine can improve
      patient outcomes.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Response rates

Secondary Outcome

 Progression free survival

Condition

Ovarian Cancer

Intervention

Vinorelbine

Study Arms / Comparison Groups

 IV Vinorelbine

Description:  IV Vinorelbine 25mg/m2

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

36

Start Date

July 1, 2017

Completion Date

July 1, 2022

Primary Completion Date

July 1, 2021

Eligibility Criteria

        Inclusion Criteria:

          1. Provided written informed consent

          2. Patients must have platinum resistant or refractory HGSOC; defined as progressive
             disease by imaging ≤ 6 months from last date of most recent platinum-based therapy or
             rising CA-125 based on GCIG criteria

          3. Have histological confirmation of high-grade serous or high-grade endometrioid or
             undifferentiated tumour of the primary peritoneum, fallopian tube cancer or ovary

          4. Molecular subtyping by Nanostring technology must confirm C5 subtype on primary
             ovarian surgical sample or a biopsy of recurrent disease

          5. Patients must not have received more than 3 prior chemotherapy regimens, which may
             include chemotherapy, biologics or other targeted therapies (this does not include
             maintenance treatment or hormonal therapy) for platinum resistant disease

          6. Measurable disease by RECIST criteria (version 1.1).

          7. At time of registration, if the patient has had previous treatment it must have been
             at least 28 days since major surgery or radiation therapy; 28 days from any other
             previous anti-cancer therapy including biologics; 14 days since hormone therapy.
             Patients must have recovered to ≤ grade 1 from their treatment-related events with the
             exception of alopecia.

          8. Age ≥ 18 years of age (Age ≥ 21 years of age for Singapore sites)

          9. Have clinically acceptable laboratory screening results within certain limits
             specified below:

               -  AST and ALT ≤ 2.5 times upper limit of normal (ULN)

               -  Total bilirubin ≤ ULN

               -  Creatinine ≤ 1.5 x UL

               -  Absolute neutrophil count ≥ 1500 cells/mm

               -  Platelets ≥ 100,000/mm3

               -  Hemoglobin ≥ 9.0 g/dl

         10. Have an ECOG performance status of ≤ 2.

         11. Women of child-producing potential must agree to use effective contraceptive methods
             prior to study entry, during study participation, and for at least 30 days after the
             last administration of study medication.

         12. Have the ability to understand the requirements of the study, provide written informed
             consent, abide by the study restrictions, and agree to return for the required
             assessments.

         13. Able to tolerate IV medication.

         14. Life expectancy greater than 6 months

        Exclusion Criteria:

          1. Women who are pregnant or nursing

          2. Previous exposure to vinorelbine

          3. Patients known to be hypersensitive to vinorelbine or any vinca alkaloids previously

          4. Persistent toxicities (≥ Common Terminology Criteria for Adverse Event (CTCAE) v4.0
             grade 1) caused by previous cancer therapy, excluding alopecia

          5. Have active, acute, or chronic clinically significant infections or bleeding.

          6. Have active angina pectoris, stroke, myocardial infarction, or any other pre-existing
             uncontrolled cardiovascular condition within the last 6 months.

          7. Have additional uncontrolled serious medical or psychiatric illness.

          8. Require therapeutic doses of anti-coagulation with warfarin or warfarin derivatives.
             However, treatment with low molecular weight heparin (LMWH) is allowed.

          9. Known symptomatic CNS metastases. Treated brain metastatis that are stable for more
             than ≥4 weeks are allowed.

         10. Psychiatric disorders that would hinder compliance with study protocol

         11. History of other malignancies within the past 5 years except for curatively treated
             skin BCC or SCC or cervical carcinoma in situ. Patients who have had curatively
             treated breast cancer, with completion of adjuvant chemotherapy more than three years
             before are allowed.

         12. Require treatment with drugs known to be potent inducers or inhibitors of CYP3A4 at
             the time of registration

         13. Subjects known to be HIV positive or with active and untreated Hepatitis B or
             Hepatitis C infection. Patients with controlled Hepatitis B or Hepatitis C infection
             on treatment with antiviral medication are allowed.
      

Gender

Female

Ages

21 Years - 99 Years

Accepts Healthy Volunteers

No

Contacts

David Tan, (65) 6779 5555, [email protected]

Location Countries

Australia

Location Countries

Australia

NCT ID

NCT03188159

Organization ID

GY01/05/16

Responsible Party

Sponsor

Study Sponsor

National University Hospital, Singapore

Collaborators

 National Cancer Centre, Singapore

Study Sponsor

David Tan, Principal Investigator, National University Hospital, Singapore

Verification Date

March 2018