PD 0360324 and Cyclophosphamide in Treating Patients With Recurrent High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

NCT02948101 | Withdrawn Phase 2 FDA Drug

• 3 other identifiers: 2016-0053NCI-2016-01928P30CA016672
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the side effects of PD 0360324 and cyclophosphamide and to see how well they work in treating patients with high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancer that has come back after a period of improvement. Immunotherapy with monoclonal antibodies, such as PD 0360324, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cyclophosphamide may stop the growth of disease by blocking the growth of new blood vessels necessary for tumor growth. Giving PD 0360324 and cyclophosphamide may work better in treating patients with high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancer.

Conditions

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

Outcome Measures

Primary Outcomes (5)

• Incidence of adverse effect

  Up to 90 days

• Density of CD8+ T cells in tumor biopsies

  Will be reported descriptively at each time point. Continuous measures will be presented with nonparametric methods such as median and interquartile range or boxplots, while correlations (Pearson's or Spearman's as indicated) will be calculated with other continuous measures. Scored or categorical measures will be tabulated.

  Up to 90 days

• Response rate

  Will be reported with a 95% confidence interval.

  Up to 90 days

• Progression-free survival

  Will be presented with a Kaplan-Meier curve.

  Up to 90 days

• Concentration-time data of PD 0360324

  Will be summarized by descriptive statistics (n, mean, standard deviation, median, minimum, and maximum).

  Up to 90 days

Study Arms (1)

Treatment (PD 0360324, cyclophosphamide)

EXPERIMENTAL

Patients receive anti-CSF1 monoclonal antibody anti-CSF1 monoclonal antibody PD 0360324 IV over 30 minutes on days 1, 8, 15, and 22. Starting on day 43, patients receive cyclophosphamide PO QD. Courses with cyclophosphamide repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Anti-CSF1 Monoclonal Antibody PD-0360324; Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis

Interventions

Anti-CSF1 Monoclonal Antibody PD-0360324 BIOLOGICAL

Given IV

Also known as: Anti-M-CSF mAb PD-0360324, PD 0360324, PD 360324, PD-0360324, PD-360,324

Treatment (PD 0360324, cyclophosphamide)

Cyclophosphamide DRUG

Given PO

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (PD 0360324, cyclophosphamide)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (PD 0360324, cyclophosphamide)

Eligibility Criteria

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

You may qualify if:

• Written informed consent
• Histology showing recurrent high grade epithelial ovarian, peritoneal, or fallopian tube cancer
• Platinum resistant or refractory disease as defined by progression of disease on a platinum-containing regimen or recurrence of disease within 180 days of previous platinum treatment
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined at least two lesions that can be accurately measured in at least one dimension (longest dimension to be recorded); each "target" lesion must be \> 20 mm when measured by palpitation or \>10 mm when measured by spiral computed tomography (CT), plain x-ray, magnetic resonance imaging (MRI), or positron emission tomography (PET)/CT; PET/CT will be acceptable at baseline if PET/CT was previously performed and available; imaging must be performed within -28 to -7 days of starting therapy; the target lesion must be distinct from other tumor areas selected for pre-treatment biopsies
• Subject must be willing to undergo protocol directed biopsies and blood draw for immune profiling
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of \>= 4 months in the attending physician's estimation
• Estimated creatinine clearance \> 40 mL/min by the Cockcroft-Gault formula
• White blood cell (WBC) \>= 3.0 x 10\^3/ul
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (\> 1500 per mm\^3)
• Platelet count \>= 100 x 10\^9/L (\> 100,000 per mm\^3)
• Hemoglobin \>= 9.0 g/dL
• Female subjects must either be of non-reproductive potential (i.e., post-menopausal by history: \>=60 years old and no menses for \> 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry
• Subject must be willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
• Signed informed consent for protocol PA13-0291

You may not qualify if:

• Absence of a biopsiable lesion as determined by radiologist
• Chemotherapy, hormonal, or biologic treatment for ovarian, fallopian tube, or primary peritoneal cancer in the last 21 days
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease \>=5 years before the first dose of study drug and of low potential risk for recurrence;
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; or
• Adequately treated carcinoma in situ without evidence of disease, e.g. cervical cancer in situ
• Current or prior use of immunosuppressive medication within 21 days before the first dose of PD 0360324, with the exceptions of intranasal and inhaled corticosteroids and systemic corticosteroids at physiological doses (defined as not exceeding 10 mg/day of prednisone, or an equivalent dose of over corticosteroid)
• Prior immunotherapy with immune checkpoint inhibitors
• Any unresolved toxicity (\> Common Terminology Criteria for Adverse Events \[CTCAE\] grade 1) from previous anti-cancer therapy with the exception of alopecia; subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripheral neuropathy)
• Subjects with an active infection requiring antibiotics or at an increased risk of latent infection that may affect safe study participation
• Subjects with existing periorbital edema
• Subjects with aspartate aminotransferase (AST) or alanine transaminase (ALT) \>= 2 x upper limit of normal (ULN)
• Subjects with creatine kinase \> ULN
• Subjects with clinically significant active ischemic heart disease, cardiac muscle disease (including cardiomyopathy or congestive heart failure) or myodegenerative disorders that may affect safe study participation
• Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days prior to study entry

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

Cyclophosphamide

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)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Amir Jazaeri

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 25, 2016
• First Posted: October 28, 2016
• Study Start: December 31, 2018
• Primary Completion: February 6, 2019
• Study Completion: February 6, 2019
• Last Updated: March 12, 2019

Record last verified: 2019-03

Locations

US (1)