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

NCT02312245 | Completed Phase 2 Results DMC

• 4 other identifiers: MC1463NCI-2014-0239914-002986R01CA184502
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 3

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.

Conditions

Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Percentage 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 Outcomes (4)

• Number of Patients Experiencing Grade 3+ Adverse Events (AE)

  9 months

• Overall Survival (OS)

  25 months

• Progression Free Survival (PFS)

  9 months

• Number of Patients With a Partial or Confirmed Response

  9 months

Other Outcomes (2)

• Enriched Avatar Response Signature in Response to Avatar-directed Therapy Using Patient Outcomes

  Up to 3 years

• Frequency (%) of Patients Who Had an Avatar Response and a Clinical Tumor Response for the Same Treatment

  Up to 3 years

Study Arms (4)

Arm A (Avatar-directed paclitaxel)

EXPERIMENTAL

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; Drug: Paclitaxel

Arm B (Avatar-directed gemcitabine hydrochloride)

EXPERIMENTAL

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

Arm C (Avatar-directed liposomal doxorubicin)

EXPERIMENTAL

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; Drug: Pegylated Liposomal Doxorubicin Hydrochloride

Arm D (Avatar-directed topotecan hydrochloride)

EXPERIMENTAL

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; Drug: Topotecan Hydrochloride

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: 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

Arm A (Avatar-directed paclitaxel); Arm C (Avatar-directed liposomal doxorubicin); Arm D (Avatar-directed topotecan hydrochloride)

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011, LY188011

Arm B (Avatar-directed gemcitabine hydrochloride)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Arm A (Avatar-directed paclitaxel)

Pegylated Liposomal Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 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

Arm C (Avatar-directed liposomal doxorubicin)

Topotecan Hydrochloride DRUG

Given IV

Also known as: Hycamptamine, Hycamtin, SKF S-104864-A, Topotecan HCl, topotecan hydrochloride (oral)

Arm D (Avatar-directed topotecan hydrochloride)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic in Arizona

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; Gemcitabine; Paclitaxel; Taxes; liposomal doxorubicin; Doxorubicin; Topotecan

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Camptothecin; Alkaloids

Results Point of Contact

• Title: S. John Weroha, M.D., Ph.D.
• Organization: Mayo Clinic

weroha.saravut@mayo.edu

(507) 284-2511

Study Officials

• John Weroha, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2014
• First Posted: December 9, 2014
• Study Start: July 21, 2015
• Primary Completion: April 24, 2023
• Study Completion: April 24, 2023
• Last Updated: December 5, 2024
• Results First Posted: December 5, 2024

Record last verified: 2024-11

Locations

US (3)