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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2014-02399 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 14-002986 | Other Identifier | Mayo Clinic Institutional Review Board | |
| MC1463 | Other Identifier | Mayo Clinic | |
| R01CA184502 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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. |
|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bevacizumab | Biological | Given IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients Experiencing Grade 3+ 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. | 9 months |
| Overall Survival (OS) |
| 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 |
Inclusion Criteria:
Exclusion Criteria:
Any of the following:
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:
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
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| Name | Affiliation | Role |
|---|---|---|
| John Weroha, M.D. | Mayo Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic in Arizona | Phoenix | Arizona | 85054 | United States | ||
| Mayo Clinic in Florida |
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| Label | URL |
|---|---|
| Mayo Clinic Clinical Trials | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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> > Bevacizumab: Given IV> > Paclitaxel: Given IV |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 28, 2018 |
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|
| Gemcitabine Hydrochloride | Drug | Given IV |
|
|
| Paclitaxel | Drug | Given IV |
|
|
| Pegylated Liposomal Doxorubicin Hydrochloride | Drug | Given IV |
|
|
| Topotecan Hydrochloride | Drug | Given IV |
|
|
OS will be estimated using the method of Kaplan-Meier. Analysis will be conducted with all arms of Avatar-directed chemotherapy pooled.
| 25 months |
| Progression Free Survival (PFS) | PFS will be estimated using the method of Kaplan-Meier. Analysis will be conducted with all arms of Avatar-directed chemotherapy pooled. | 9 months |
| Number of Patients With a Partial or Confirmed Response | 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. | 9 months |
Overall concordance rate and confidence interval will be reported. |
| Up to 3 years |
| Jacksonville |
| Florida |
| 32224 |
| United States |
| Mayo Clinic in Rochester | Rochester | Minnesota | 55905 | United States |
| 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.> > Gemcitabine Hydrochloride: Given IV |
| FG002 | 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.> > Bevacizumab: Given IV> > Pegylated Liposomal Doxorubicin Hydrochloride: Given IV |
| FG003 | 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.> > Bevacizumab: Given IV> > Topotecan Hydrochloride: Given IV |
| COMPLETED |
|
| NOT COMPLETED |
|
|
All patients that were enrolled were analyzed
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| ID | Title | Description |
|---|---|---|
| BG000 | 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> > Bevacizumab: Given IV> > Paclitaxel: Given IV |
| BG001 | 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.> > Gemcitabine Hydrochloride: Given IV |
| BG002 | 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.> > Bevacizumab: Given IV> > Pegylated Liposomal Doxorubicin Hydrochloride: Given IV |
| BG003 | 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.> > Bevacizumab: Given IV> > Topotecan Hydrochloride: Given IV |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Tumor Histology Type | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | All patients that were eligible and began treatment were analyzed | Posted | Count of Participants | Participants | 24 weeks |
|
|
| ||||||||||||||||||||||||||||||||
| Secondary | Number of Patients Experiencing Grade 3+ 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. | All patients that were eligible and began treatment were analyzed | Posted | Count of Participants | Participants | 9 months |
| ||||||||||||||||||||||||||||||||||
| Secondary | Overall Survival (OS) | OS will be estimated using the method of Kaplan-Meier. Analysis will be conducted with all arms of Avatar-directed chemotherapy pooled. | All patients that were eligible and began treatment were analyzed | Posted | Median | 95% Confidence Interval | months | 25 months |
| |||||||||||||||||||||||||||||||||
| Secondary | Progression Free Survival (PFS) | PFS will be estimated using the method of Kaplan-Meier. Analysis will be conducted with all arms of Avatar-directed chemotherapy pooled. | All patients that were eligible and began treatment were analyzed | Posted | Median | 95% Confidence Interval | months | 9 months |
| |||||||||||||||||||||||||||||||||
| Secondary | Number of Patients With a Partial or Confirmed Response | 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. | All patients that were eligible and began treatment were analyzed | Posted | Count of Participants | Participants | 9 months |
| ||||||||||||||||||||||||||||||||||
| Other Pre-specified | 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. | Not Posted | Up to 3 years | Participants | |||||||||||||||||||||||||||||||||||||
| Other Pre-specified | 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. | Not Posted | Up to 3 years | Participants |
25 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A (Avatar-directed Paclitaxel) | Paclitaxel: Given IV | 1 | 2 | 1 | 2 | 1 | 2 |
| EG001 | Arm B (Avatar-directed Gemcitabine Hydrochloride) | Gemcitabine Hydrochloride: Given IV | 1 | 1 | 0 | 1 | 1 | 1 |
| EG002 | Arm D (Avatar-directed Topotecan Hydrochloride) | Topotecan Hydrochloride: Given IV | 6 | 9 | 3 | 9 | 4 | 9 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | MedDRA 12.0 | Systematic Assessment |
| |
| Colonic obstruction | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
| |
| Gastric perforation | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
| |
| Creatinine increased | Investigations | MedDRA 12.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 12.0 | Systematic Assessment |
| |
| Hyponatremia | Metabolism and nutrition disorders | MedDRA 12.0 | Systematic Assessment |
| |
| Neoplasms benign, mal, uncpec - Oth spec | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 12.0 | Systematic Assessment |
| |
| Confusion | Psychiatric disorders | MedDRA 12.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | MedDRA 12.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 12.0 | Systematic Assessment |
| |
| Alkaline phosphatase increased | Investigations | MedDRA 12.0 | Systematic Assessment |
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| Lymphocyte count decreased | Investigations | MedDRA 12.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 12.0 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 12.0 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| S. John Weroha, M.D., Ph.D. | Mayo Clinic | (507) 284-2511 | weroha.saravut@mayo.edu |
| Aug 15, 2024 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D005185 | Fallopian Tube Neoplasms |
| D010051 | Ovarian Neoplasms |
| ID | Term |
|---|---|
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005184 | Fallopian Tube Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D004701 | Endocrine Gland Neoplasms |
| D010049 | Ovarian Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
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| ID | Term |
|---|---|
| D000068258 | Bevacizumab |
| D007074 | Immunoglobulin G |
| D004220 | Disulfides |
| D000093542 | Gemcitabine |
| D017239 | Paclitaxel |
| D013660 | Taxes |
| C506643 | liposomal doxorubicin |
| D004317 | Doxorubicin |
| D019772 | Topotecan |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D007132 | Immunoglobulin Isotypes |
| D013440 | Sulfides |
| D000838 | Anions |
| D007477 | Ions |
| D004573 | Electrolytes |
| D007287 | Inorganic Chemicals |
| D006862 | Hydrogen Sulfide |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D004467 | Economics |
| D004472 | Health Care Economics and Organizations |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D002166 | Camptothecin |
| D000470 | Alkaloids |
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| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Fallopian tube (serous) |
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| Ovarian (other) |
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