The Effect of Neoadjuvant DMPA on Glandular Cellularity in Women Awaiting Hysterectomy

NCT02335203 | Unknown Phase 2

• 1 other identifier: 14-0099
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

Objective: To compare pre- and post-treatment glandular cellularity in women with complex atypical hyperplasia or grade 1-2 endometrial adenocarcinoma who are treated with intramuscular depot medroxyprogesterone acetate (DMPA) versus placebo injection prior to hysterectomy. The secondary objective is to compare various other outcomes including molecular, histologic, pathologic and clinical endpoints in women treated with DMPA versus placebo prior to hysterectomy. Hypothesis: Patients treated with DMPA will have significantly decreased glandular cellularity post-treatment when compared to patients treated with placebo injection. Patients treated with DMPA will exhibit previously described changes in molecular tumor marker expression patterns and other characteristic histologic changes. Patients treated with DMPA will report less bothersome vaginal bleeding prior to surgery when compared to patients treated with placebo injection. Study Design: Double blinded randomized controlled trial Population: Women being treated at the Women and Infants Program in Women's Oncology who have a biopsy-proven diagnosis of complex atypical hyperplasia or grade 1-2 endometrial adenocarcinoma with disease clinically confined to the uterus, with a plan to undergo hysterectomy. Study Period: February 2015 to June 2016

Conditions

Grade 1 Endometrial Endometrioid Adenocarcinoma; Grade 2 Endometrial Endometrioid Adenocarcinoma; Complex Atypical Endometrial Hyperplasia

Outcome Measures

Primary Outcomes (1)

• Change in glandular cellularity

  Histologic analysis of glandular cellularity in hysterectomy specimens as compared to pre-hysterectomy endometrial tissue

  2-3 weeks after hysterectomy

Secondary Outcomes (16)

• Change in mitotic index

  2-3 weeks after hysterectomy

• Histologic grade

  2-3 weeks after hysterectomy

• Depth of invasion

  2-3 weeks after hysterectomy

• Tumor size

  2-3 weeks after hysterectomy

• Lymph node involvement

  2-3 weeks after hysterectomy

Study Arms (2)

Depot medroxyprogesterone acetate

EXPERIMENTAL

Women randomized to receive one intramuscular injection of 400mg depot medroxyprogesterone acetate prior to hysterectomy.

Drug: Depot medroxyprogesterone acetate

Placebo injection

PLACEBO COMPARATOR

Women randomized to receive one intramuscular injection of 1mL normal saline prior to hysterectomy.

Other: Placebo

Interventions

Depot medroxyprogesterone acetate DRUG

One injection intragluteally of 400mg depot medroxyprogesterone acetate at the time of the patient's first visit with the Program in Womens' Oncology

Also known as: Depo Provera, DMPA

Depot medroxyprogesterone acetate

Placebo OTHER

One injection intragluteally of 1mL Normal Saline (0.9% Sodium Chloride) at the time of the patient's first visit with the Program in Womens' Oncology

Also known as: 0.9% Sodium Chloride

Placebo injection

Eligibility Criteria

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

You may qualify if:

• Patient at the Women and Infants Program in Women's Oncology
• Biopsy-proven complex atypical hyperplasia or grade 1 or grade 2 endometrial adenocarcinoma with endometrioid histology
• Disease clinically confined to the uterus (no physical exam findings or imaging to suggest extrauterine disease)
• Ages 18 and older
• Plan for hysterectomy at Women and Infants Hospital of Rhode Island
• Able to read English or Spanish
• Able to give informed consent for involvement in the study

You may not qualify if:

• Allergic to medroxyprogesterone acetate
• Known sensitivity to any component of depot medroxyprogesterone acetate
• History of breast cancer, hepatic disease, uncontrolled hypertension, osteoporosis or strong osteoporotic risk factors including anorexia nervosa, rheumatoid arthritis and chronic glucocorticoid use
• Treatment with any progesterone or progesterone analogue in past 12 months

Sponsors & Collaborators

• Women and Infants Hospital of Rhode Island: lead

Study Sites (1)

Women and Infants Hospital, Program in Women's Oncology

Providence, Rhode Island, 02905, United States

Location

Related Publications (9)

• Elit LM, O'Leary EM, Pond GR, Seow HY. Impact of wait times on survival for women with uterine cancer. J Clin Oncol. 2014 Jan 1;32(1):27-33. doi: 10.1200/JCO.2013.51.3671. Epub 2013 Nov 25.

  PMID: 24276779 BACKGROUND

• Gunderson CC, Dutta S, Fader AN, Maniar KP, Nasseri-Nik N, Bristow RE, Diaz-Montes TP, Palermo R, Kurman RJ. Pathologic features associated with resolution of complex atypical hyperplasia and grade 1 endometrial adenocarcinoma after progestin therapy. Gynecol Oncol. 2014 Jan;132(1):33-7. doi: 10.1016/j.ygyno.2013.11.033. Epub 2013 Dec 4.

  PMID: 24316307 BACKGROUND

• Loprinzi CL, Levitt R, Barton D, Sloan JA, Dakhil SR, Nikcevich DA, Bearden JD 3rd, Mailliard JA, Tschetter LK, Fitch TR, Kugler JW. Phase III comparison of depomedroxyprogesterone acetate to venlafaxine for managing hot flashes: North Central Cancer Treatment Group Trial N99C7. J Clin Oncol. 2006 Mar 20;24(9):1409-14. doi: 10.1200/JCO.2005.04.7324. Epub 2006 Feb 27.

  PMID: 16505409 BACKGROUND

• O'Leary E, Elit L, Pond G, Seow H. The wait time creep: changes in the surgical wait time for women with uterine cancer in Ontario, Canada, during 2000-2009. Gynecol Oncol. 2013 Oct;131(1):151-7. doi: 10.1016/j.ygyno.2013.06.036. Epub 2013 Jul 7.

  PMID: 23838037 BACKGROUND

• Palmieri D, Halverson DO, Ouatas T, Horak CE, Salerno M, Johnson J, Figg WD, Hollingshead M, Hursting S, Berrigan D, Steinberg SM, Merino MJ, Steeg PS. Medroxyprogesterone acetate elevation of Nm23-H1 metastasis suppressor expression in hormone receptor-negative breast cancer. J Natl Cancer Inst. 2005 May 4;97(9):632-42. doi: 10.1093/jnci/dji111.

  PMID: 15870434 BACKGROUND

• Park JY, Kim DY, Kim TJ, Kim JW, Kim JH, Kim YM, Kim YT, Bae DS, Nam JH. Hormonal therapy for women with stage IA endometrial cancer of all grades. Obstet Gynecol. 2013 Jul;122(1):7-14. doi: 10.1097/AOG.0b013e3182964ce3.

  PMID: 23743459 BACKGROUND

• Rosenfield A, Maine D, Rochat R, Shelton J, Hatcher RA. The Food and Drug Administration and medroxyprogesterone acetate. What are the issues? JAMA. 1983 Jun 3;249(21):2922-8.

  PMID: 6221125 BACKGROUND

• Wheeler DT, Bristow RE, Kurman RJ. Histologic alterations in endometrial hyperplasia and well-differentiated carcinoma treated with progestins. Am J Surg Pathol. 2007 Jul;31(7):988-98. doi: 10.1097/PAS.0b013e31802d68ce.

  PMID: 17592264 BACKGROUND

• Zaino RJ, Brady WE, Todd W, Leslie K, Fischer EG, Horowitz NS, Mannel RS, Walker JL, Ivanovic M, Duska LR. Histologic effects of medroxyprogesterone acetate on endometrioid endometrial adenocarcinoma: a Gynecologic Oncology Group study. Int J Gynecol Pathol. 2014 Nov;33(6):543-53. doi: 10.1097/PGP.0000000000000177.

  PMID: 25272292 BACKGROUND

MeSH Terms

Interventions

Medroxyprogesterone Acetate; N,N-dimethyl-4-anisidine; Sodium Chloride

Intervention Hierarchy (Ancestors)

Medroxyprogesterone; Hydroxyprogesterones; Progesterone; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Stephen Fiascone, MD

  Department of medical education

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD in Department of Medical Education; OB/GYN Residency Program

Study Record Dates

• First Submitted: December 22, 2014
• First Posted: January 9, 2015
• Study Start: February 1, 2015
• Primary Completion: March 1, 2016
• Study Completion: June 1, 2018
• Last Updated: September 20, 2016

Record last verified: 2016-09

Locations

US (1)