Clinical Trials /

Avatar-Directed Chemotherapy in Treating Patients With Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

NCT02312245

Description:

This phase II trial studies how well Avatar-directed chemotherapy works in treating patients with ovarian, primary peritoneal, or fallopian tube cancer that does not respond to platinum anti-cancer drugs. Drugs used in chemotherapy, such as paclitaxel, gemcitabine hydrochloride, pegylated liposomal doxorubicin hydrochloride, topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Using an Avatar, a living tumor sample with similar genetic characteristics to the original tumor, may help determine which chemotherapy is most effective.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Avatar-Directed Chemotherapy in Treating Patients With Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
  • Official Title: Avatar-Directed Chemotherapy in Platinum-Resistant Ovarian, Primary Peritoneal and Fallopian Tube Cancers

Clinical Trial IDs

  • ORG STUDY ID: MC1463
  • SECONDARY ID: NCI-2014-02399
  • SECONDARY ID: Mod14-002986-03
  • SECONDARY ID: MC1463
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT02312245

Conditions

  • Recurrent Fallopian Tube Carcinoma
  • Recurrent Ovarian Carcinoma
  • Recurrent Primary Peritoneal Carcinoma

Interventions

DrugSynonymsArms
BevacizumabAnti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGFArm A (Avatar-directed paclitaxel)
Gemcitabine HydrochloridedFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011, LY188011Arm B (Avatar-directed gemcitabine hydrochloride)
PaclitaxelAnzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol KonzentratArm A (Avatar-directed paclitaxel)
Pegylated Liposomal Doxorubicin HydrochlorideATI-0918, Caelyx, DOX-SL, Doxil, Doxilen, Doxorubicin HCl Liposome, Doxorubicin Hydrochloride Liposome, Duomeisu, Evacet, LipoDox, Liposomal Adriamycin, Liposomal Doxorubicin Hydrochloride, Liposomal-Encapsulated Doxorubicin, Pegylated Doxorubicin HCl Liposome, S-Liposomal Doxorubicin, Stealth Liposomal Doxorubicin, TLC D-99Arm C (Avatar-directed liposomal doxorubicin)
Topotecan HydrochlorideHycamptamine, Hycamtin, SKF S-104864-A, Topotecan HCl, topotecan hydrochloride (oral)Arm D (Avatar-directed topotecan hydrochloride)

Purpose

This phase II trial studies how well Avatar-directed chemotherapy works in treating patients with ovarian, primary peritoneal, or fallopian tube cancer that does not respond to platinum anti-cancer drugs. Drugs used in chemotherapy, such as paclitaxel, gemcitabine hydrochloride, pegylated liposomal doxorubicin hydrochloride, topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Using an Avatar, a living tumor sample with similar genetic characteristics to the original tumor, may help determine which chemotherapy is most effective.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the response rate of Avatar-directed salvage chemotherapy in patients with
      platinum-resistant ovarian, primary peritoneal and fallopian tube cancers.

      SECONDARY OBJECTIVES:

      I. To determine the progression-free survival of patients with platinum-resistant ovarian,
      primary peritoneal and fallopian tube cancers receiving Avatar-directed salvage chemotherapy.

      II. To determine the overall survival of patients with platinum-resistant ovarian, primary
      peritoneal and fallopian tube cancers receiving Avatar-directed salvage chemotherapy.

      III. To determine the adverse events for patients with platinum-resistant ovarian, primary
      peritoneal and fallopian tube cancers receiving Avatar-directed salvage chemotherapy.

      IV. To determine the correlation between patient response and response in their Avatar.

      V. To enrich the Avatar response signature in response to Avatar-directed therapy using
      patient outcomes.

      VI. To compare the response rates between patients who did or did not receive bevacizumab
      treatment.

      OUTLINE: Patients are assigned to 1 of 4 treatment arms as directed by Avatar results.

      ARM A: Patients receive paclitaxel intravenously (IV) over 1-96 hours on days 1, 8, and 15.
      Patients may also receive bevacizumab IV over 90 minutes on days 1 and 15. Courses repeat
      every 28 days in the absence of disease progression or unacceptable toxicity

      ARM B: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15.
      Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

      ARM C: Patients receive pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on
      day 1. Patients may also receive bevacizumab IV over 90 minutes on days 1 and 15. Courses
      repeat every 28 days in the absence of disease progression or unacceptable toxicity.

      ARM D: Patients receive topotecan hydrochloride IV over 30 minutes on days 1-5 every 21 days
      or days 1, 8, and 15 every 28 days. Patients may also receive bevacizumab IV over 90 minutes
      on day 1 every 21 days or days 1 and 15 every 28 days. Courses repeat every 21 or 28 days in
      the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3-6 months for 3 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (Avatar-directed paclitaxel)ExperimentalPatients receive paclitaxel IV over 1-96 hours on days 1, 8, and 15. Patients may also receive bevacizumab IV over 90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
  • Bevacizumab
  • Paclitaxel
Arm B (Avatar-directed gemcitabine hydrochloride)ExperimentalPatients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Gemcitabine Hydrochloride
Arm C (Avatar-directed liposomal doxorubicin)ExperimentalPatients receive pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1. Patients may also receive bevacizumab IV over 90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Bevacizumab
  • Pegylated Liposomal Doxorubicin Hydrochloride
Arm D (Avatar-directed topotecan hydrochloride)ExperimentalPatients receive topotecan hydrochloride IV over 30 minutes on days 1-5 every 21 days or days 1, 8, and 15 every 28 days. Patients may also receive bevacizumab IV over 90 minutes on day 1 every 21 days or days 1 and 15 every 28 days. Courses repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity.
  • Bevacizumab
  • Topotecan Hydrochloride

Eligibility Criteria

        Inclusion Criteria:

          -  Histologic confirmation of ovarian, primary peritoneal or fallopian tube cancer of any
             subtype

          -  Prior consent to have tumors used for unspecified future research

          -  Ability to provide written informed consent

          -  Willing to agree to periodic contact with a member of the study team during the period
             that the cancer has not recurred and/or has not become platinum resistant

          -  Willing to agree that the local medical oncologist may be informed that patient has
             agreed to participate in the study

          -  Platinum resistant or refractory ovarian, primary peritoneal or fallopian tube cancer
             of any subtype; Note: platinum-sensitive disease is allowed in cases where there is a
             contraindication to platinum-based therapy (i.e., allergy to platinum); this must be
             reviewed and approved by the Principal Investigator

          -  Successful Avatar engraftment with successful expansion and treatment outcome of
             Avatar therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status (ECOG performance status
             [PS]) of 0, 1 or 2

          -  Measurable disease or non-measurable disease; for patients with non-measureable
             disease, they must also have a cancer antigen (CA)-125 measurement of > 35 U/mL or 2 X
             their documented nadir on 2 separate measurements 1 week apart

          -  The following laboratory values obtained =< 21 days prior to registration; complete
             blood count (CBC), sodium, potassium, aspartate aminotransferase (AST), bilirubin and
             creatinine are to be obtained pre-study; Note: treatment initiation and dosing
             modification should be performed at the individual investigators discretion and be
             consistent with the product label and their medical practice

          -  Negative urine or serum pregnancy test performed =< 7 days prior to registration, for
             women of child bearing potential only

          -  Willing to return to enrolling institution for follow-up or have a local physician
             willing to submit response and outcome data; Note: any and all therapy, potentially in
             its entirety, may be conducted outside of the Mayo Clinic

        Exclusion Criteria:

          -  Any of the following:

               -  Pregnant women

               -  Nursing women

          -  Prior treatment with Doxil, topotecan, Gemzar or Taxol chemotherapy for
             platinum-resistant cancer; Note: Allowed prior therapy with Doxil or Gemzar if given
             for platinum sensitive disease in combination with a platinum drug AND the Avatar data
             indicates a drug other than Doxil or Gemzar would be effective; Note: Allowed prior
             therapies for patients following confirmation of platinum-resistant cancer include:

               -  Therapeutic antibodies, such as bevacizumab

               -  Small molecule kinase inhibitors, such as pazopanib

               -  Vaccines and immunotherapy All of these exceptions should be confirmed with the
                  Principal Investigator (PI) prior to registration

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

          -  Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)
             positive and currently receiving antiretroviral therapy; Note: patients known to be
             HIV positive, but without clinical evidence of an immunocompromised state, are
             eligible for this trial

          -  Uncontrolled intercurrent illness judged by the treating investigator to preclude
             treatment with chemotherapy

          -  Receiving any other investigational agent which would be considered as a treatment for
             the primary neoplasm

          -  Other active malignancy =< 3 years prior to registration; EXCEPTIONS: non-melanotic
             skin cancer or carcinoma-in-situ of the cervix; Note: if there is a history of prior
             malignancy, they must not be receiving treatment for their cancer
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of patients with a confirmed tumor response, defined as complete response or partial response estimated using Response Evaluation Criteria in Solid Tumors 1.1 criteria
Time Frame:24 weeks
Safety Issue:
Description:Estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the exact Binomial method. The primary analysis will pool across all patients, and tumor response rate by treatment arm will also be looked at in an exploratory fashion.

Secondary Outcome Measures

Measure:Incidence of adverse events (AE)
Time Frame:Up to 3 years
Safety Issue:
Description:Maximum grade for each type of AE will be recorded for each patient, and frequency tables will be reviewed to determine AE patterns.
Measure:Overall survival (OS)
Time Frame:Time from registration to death from any cause, assessed up to 3 years
Safety Issue:
Description:OS will be estimated using the method of Kaplan-Meier.
Measure:Progression free survival (PFS)
Time Frame:Time from registration to the first of either disease progression or death from any cause, assessed up to 3 years
Safety Issue:
Description:PFS will be estimated using the method of Kaplan-Meier.
Measure:Response rates
Time Frame:Up to 3 years
Safety Issue:
Description:The Chi-square or Fisher's Exact test will be used to compare the response rates between patients who did or did not receive bevacizumab treatment. The response rates will also be reported by treatment type (bevacizumab or no bevacizumab).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mayo Clinic

Last Updated

July 23, 2019