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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02312245
Recruitment Status : Recruiting
First Posted : December 9, 2014
Last Update Posted : July 29, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Biological: Bevacizumab Drug: Gemcitabine Hydrochloride Drug: Paclitaxel Drug: Pegylated Liposomal Doxorubicin Hydrochloride Drug: Topotecan Hydrochloride Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Avatar-Directed Chemotherapy in Platinum-Resistant Ovarian, Primary Peritoneal and Fallopian Tube Cancers
Actual Study Start Date : July 21, 2015
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021


Arm Intervention/treatment
Experimental: Arm A (Avatar-directed paclitaxel)
Patients 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
Biological: Bevacizumab
Given IV
Other Names:
  • Anti-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-VEGF

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Experimental: Arm B (Avatar-directed gemcitabine hydrochloride)
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.
Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011
  • LY188011

Experimental: Arm C (Avatar-directed liposomal doxorubicin)
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.
Biological: Bevacizumab
Given IV
Other Names:
  • Anti-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-VEGF

Drug: Pegylated Liposomal Doxorubicin Hydrochloride
Given IV
Other Names:
  • ATI-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-99

Experimental: Arm D (Avatar-directed topotecan hydrochloride)
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.
Biological: Bevacizumab
Given IV
Other Names:
  • Anti-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-VEGF

Drug: Topotecan Hydrochloride
Given IV
Other Names:
  • Hycamptamine
  • Hycamtin
  • SKF S-104864-A
  • Topotecan HCl
  • topotecan hydrochloride (oral)




Primary Outcome Measures :
  1. 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 ]
    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 :
  1. Incidence of adverse events (AE) [ Time Frame: Up to 3 years ]
    Maximum grade for each type of AE will be recorded for each patient, and frequency tables will be reviewed to determine AE patterns.

  2. Overall survival (OS) [ Time Frame: Time from registration to death from any cause, assessed up to 3 years ]
    OS will be estimated using the method of Kaplan-Meier.

  3. 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 ]
    PFS will be estimated using the method of Kaplan-Meier.

  4. Response rates [ Time Frame: Up to 3 years ]
    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).


Other Outcome Measures:
  1. Enriched Avatar response signature in response to Avatar-directed therapy using patient outcomes [ Time Frame: Up to 3 years ]
    This will be an exploratory analysis that will use the outcome data from this trial to inform future work using Avatar directed therapy.

  2. Frequency (%) of patients who had an Avatar response and a clinical tumor response for the same treatment [ Time Frame: Up to 3 years ]
    Overall concordance rate and confidence interval will be reported.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

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): NCT02312245


Locations
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United States, Arizona
Mayo Clinic Recruiting
Phoenix, Arizona, United States, 85054
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: John K. Camoriano         
United States, Florida
Mayo Clinic Recruiting
Jacksonville, Florida, United States, 32224
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Gerardo Colon-Otero         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Saravut J. Weroha         
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Saravut Weroha Mayo Clinic
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Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT02312245    
Other Study ID Numbers: MC1463
NCI-2014-02399 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Mod14-002986-03
MC1463 ( Other Identifier: Mayo Clinic )
R01CA184502 ( U.S. NIH Grant/Contract )
First Posted: December 9, 2014    Key Record Dates
Last Update Posted: July 29, 2020
Last Verified: July 2020
Additional relevant MeSH terms:
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Carcinoma
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Fallopian Tube Diseases
Adnexal Diseases
Gemcitabine
Paclitaxel
Bevacizumab
Doxorubicin
Liposomal doxorubicin
Albumin-Bound Paclitaxel
Topotecan
Antineoplastic Agents, Immunological
Endothelial Growth Factors
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunoglobulin G
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors