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

Sponsor

Mayo Clinic (Other)

Overall Status

Recruiting

CT.gov ID

NCT02312245

Collaborator

National Cancer Institute (NCI) (NIH)

240

Enrollment

Locations

Arms

95.8

Anticipated Duration (Months)

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

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:

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

SECONDARY OBJECTIVES:

To determine the progression-free survival of patients with platinum-resistant ovarian, primary peritoneal and fallopian tube cancers receiving Avatar-directed salvage chemotherapy.
To determine the overall survival of patients with platinum-resistant ovarian, primary peritoneal and fallopian tube cancers receiving Avatar-directed salvage chemotherapy.
To determine the adverse events for patients with platinum-resistant ovarian, primary peritoneal and fallopian tube cancers receiving Avatar-directed salvage chemotherapy.
To determine the correlation between patient response and response in their Avatar.
To enrich the Avatar response signature in response to Avatar-directed therapy using patient outcomes.
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.

Study Design

Study Type:

Interventional

Anticipated 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 :

Jul 21, 2015

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 15, 2023

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

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 [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

Incidence of adverse events (AE) [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.
Overall survival (OS) [Time from registration to death from any cause, assessed up to 3 years]
OS will be estimated using the method of Kaplan-Meier.
Progression free survival (PFS) [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.
Response rates [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

Enriched Avatar response signature in response to Avatar-directed therapy using patient outcomes [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.
Frequency (%) of patients who had an Avatar response and a clinical tumor response for the same treatment [Up to 3 years]
Overall concordance rate and confidence interval will be reported.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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