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

Avatar-Directed Chemotherapy in Platinum-Resistant Ovarian, Primary Peritoneal and Fallopian Tube Cancers

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma
• Intervention / Treatment: Drug: Pegylated Liposomal Doxorubicin Hydrochloride; Drug: Paclitaxel; Drug: Gemcitabine Hydrochloride; Biological: Bevacizumab; Drug: Topotecan Hydrochloride

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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	Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Biological: Bevacizumab; Given IV; Other Names: Avastin; Anti-VEGF; Anti-VEGF Humanized Monoclonal Antibody; Anti-VEGF rhuMAb; 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
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: Gemzar; dFdCyd; Difluorodeoxycytidine Hydrochloride; 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.	Drug: Pegylated Liposomal Doxorubicin Hydrochloride; Given IV; Other Names: ATI-0918; Caelyx; DOX-SL; Doxil; Doxilen; Doxorubicin HCl Liposome; Duomeisu; Evacet; LipoDox; Liposomal Adriamycin; Liposomal-Encapsulated Doxorubicin; Pegylated Doxorubicin HCl Liposome; S-Liposomal Doxorubicin; Stealth Liposomal Doxorubicin; TLC D-99; Doxorubicin Hydrochloride Liposome; Liposomal Doxorubicin Hydrochloride; Biological: Bevacizumab; Given IV; Other Names: Avastin; Anti-VEGF; Anti-VEGF Humanized Monoclonal Antibody; Anti-VEGF rhuMAb; 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
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: Avastin; Anti-VEGF; Anti-VEGF Humanized Monoclonal Antibody; Anti-VEGF rhuMAb; 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: Hycamtin; Hycamptamine; SKF S-104864-A; Topotecan HCl; topotecan hydrochloride (oral)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AE)	Maximum grade for each type of AE will be recorded for each patient, and frequency tables will be reviewed to determine AE patterns.	Up to 3 years
Overall survival (OS)	OS will be estimated using the method of Kaplan-Meier.	Time from registration to death from any cause, assessed up to 3 years
Progression free survival (PFS)	PFS will be estimated using the method of Kaplan-Meier.	Time from registration to the first of either disease progression or death from any cause, assessed up to 3 years
Response rates	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).	Up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Enriched Avatar response signature in response to Avatar-directed therapy using patient outcomes	This will be an exploratory analysis that will use the outcome data from this trial to inform future work using Avatar directed therapy.	Up to 3 years
Frequency (%) of patients who had an Avatar response and a clinical tumor response for the same treatment	Overall concordance rate and confidence interval will be reported.	Up to 3 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2015
• Primary Completion (Actual): April 24, 2023
• Study Completion (Actual): April 24, 2023

Study Registration Dates

• First Submitted: December 4, 2014
• First Submitted That Met QC Criteria: December 4, 2014
• First Posted (Estimate): December 9, 2014

Study Record Updates

• Last Update Posted (Estimate): May 4, 2023
• Last Update Submitted That Met QC Criteria: May 3, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Disease Attributes; Adnexal Diseases; Fallopian Tube Diseases; Carcinoma; Recurrence; Fallopian Tube Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antibiotics, Antineoplastic; Topoisomerase I Inhibitors; Gemcitabine; Paclitaxel; Antibodies; Immunoglobulins; Bevacizumab; Albumin-Bound Paclitaxel; Doxorubicin; Liposomal doxorubicin; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Topotecan; Immunoglobulin G; Endothelial Growth Factors
• Other Study ID Numbers: MC1463 (Other Identifier: Mayo Clinic); NCI-2014-02399 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); Mod14-002986-03; R01CA184502 (U.S. NIH Grant/Contract)