Study of Immune Response Modifier in the Treatment of Breast, Ovarian, Endometrial and Cervical Cancers

Study Description

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Brief Summary:

The purpose of this study is to evaluate the anti-tumor activity of 852A when used to treat metastatic breast, ovarian, endometrial or cervical cancer not responding to standard treatment.

Condition or disease	Intervention/treatment	Phase
Breast Cancer; Ovarian Cancer; Endometrial Cancer; Cervical Cancer	Drug: 852A	Phase 2

Detailed Description:

852A will be administered as a subcutaneous injection (SC) 2 times per week for 12 weeks (24 doses) with provisions for dose escalation or reduction based on tolerability.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	15 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase II Study of 852A Administered Subcutaneously in Patients With Metastatic Refractory Breast, Ovarian, Endometrial and Cervical Cancers
Study Start Date :	April 2006
Actual Primary Completion Date :	December 2007
Actual Study Completion Date :	December 2008

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Intent-To-Treat; Patients treated with at least one dose - 852A subcutaneous injection.	Drug: 852A; 0.2% 852a subcutaneous injection, 2 times per week for 12 weeks (24 doses) starting at 0.6 mg/m2; subsequent dose escalation for additional courses may be increased by 0.2 mg/m2 not to exceed 1.2 mg/m2.; Other Names: TLR-7; Toll-like receptor-7
Experimental: Evaluable Cohort; Patients who received all 24 doses of 852A per protocol.	Drug: 852A; 0.2% 852a subcutaneous injection, 2 times per week for 12 weeks (24 doses) starting at 0.6 mg/m2; subsequent dose escalation for additional courses may be increased by 0.2 mg/m2 not to exceed 1.2 mg/m2.; Other Names: TLR-7; Toll-like receptor-7

Outcome Measures

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Primary Outcome Measures :

1. Patients With Tumor Response (Response Evaluation Criteria in Solid Tumors) Who Received All 24 Doses of 852A. [ Time Frame: after 12 weeks (24 doses of 852A) ]
   Assessment of anti-tumor activity of 852A using Response Evaluation Criteria in Solid Tumors (RECIST) criteria to evaluate tumor response after 24 doses. Complete Response (CR)= disappearance of all target lesions, Partial Response (PR) = at least 30% decrease in sum of longest diameter of target lesions, Progressive Disease (PD) = at least 25% increase in sum of longest diameter of target lesions, Stable Disease = neither PR or PD.

Secondary Outcome Measures :

1. Mean Difference Values for Interleukin 1 Receptor Antagonist (IKL1ra) [ Time Frame: Prior to Dose 1 and 6 hours after Dose 1 ]
   Measures the difference of IL1ra (cytokine) values as a means of immune activation pre-treatment and 6 hours post-treatment in patients that received at least one dose of study treatment with 852A.
2. Mean Difference Values for 10 kDa Interferon-gamma-induced Protein (IP-10) [ Time Frame: Prior to Dose 1 and 6 Hours Post-Dose ]
   Measures differences in IP-10 (cytokine) values as a means of immune activation pre-treatment and 6 hours post-treatment in patients that received at least one dose of study treatment with 852A.
3. Mean Difference Values for Macrophage Inflammatory Protein-1 Alpha (MIP-1a) [ Time Frame: Prior to Dose 1 and 6 Hours Post-Dose ]
   Measures difference in MIP-1a (cytokine) values as a means of immune activation pre-treatment and 6 hours post-treatment in patients that received at least one dose of study treatment with 852A.
4. Mean Difference Values for Macrophage Inflammatory Protein-1 Beta (MIP-1b) [ Time Frame: Prior to Dose 1 and 6 Hours Post-Dose ]
   Measures difference in Macrophage Inflammatory Protein-1 Beta (cytokine) values as a means of immune activation pre-treatment and 6 hours post-treatment in patients that received at least one dose of study treatment with 852A.
5. Mean Difference Values for Soluble CD40 Ligand (sCD40L) [ Time Frame: Prior to Dose 1 and 6 Hours Post-Dose ]
   Measures difference in Soluble CD40 ligand (cytokine) values as a means of immune activation pre-treatment and 6 hours post-treatment in patients that received at least one dose of study treatment with 852A.
6. Mean Difference Values for Tumor Necrosis Factor-alpha (TNF-a) [ Time Frame: Prior to Dose 1 and 6 Hours Post-Dose ]
   Measures difference in Tumor necrosis factor-alpha (cytokine) values as a means of immune activation pre-treatment and 6 hours post-treatment in patients that received at least one dose of study treatment with 852A.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Adequate performance status:

  • Breast - Karnofsky score > 50;
  • Ovarian, endometrial or cervical - Gynecologic Oncology Group (GOG) performance score ≤2
• If female and of childbearing potential, are willing to use adequate contraception (hormonal, barrier method, abstinence) prior to study entry and for the duration of study participation.
• Normal organ function within 14 days of study entry

• Diagnosis of one of the following malignancies:

  • Metastatic breast cancer (BR)
  • Metastatic ovarian cancer (OV)
  • Metastatic endometrial cancer (EM)
  • Metastatic cervical cancer (CX)

Breast Cancer Inclusion Criteria:

• Measurable metastatic disease (>1cm) in at least one site other than bone-only
• Progression on or failure to respond to at least one previous chemotherapy regimen for metastatic disease
• Progression on prior therapy with a hormonal agent if estrogen receptor or progesterone receptor positive, and/or with trastuzumab if HER2-neu positive. If patient has progressed through hormone or trastuzumab therapy only, must have received one chemotherapy regimen.

Ovarian Cancer Inclusion Criteria:

• Measurable metastatic disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
• Primary tumor must have been diagnosed histologically as either epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (not borderline or low malignant potential epithelial carcinoma).
• Subjects must have failed at least two previous chemotherapy regimens. Paclitaxel must have been a component of one or both regimens and cisplatin or carboplatin must have been a component of one or both regimens.

Endometrial Cancer Inclusion Criteria:

• Measurable metastatic disease
• Histologically proven recurrent or persistent endometrial cancer that is not amenable to curative treatment with surgery and/or radiation therapy AND has failed 2 previous treatment regimens

Cervical Cancer Inclusion Criteria:

• Measurable metastatic disease
• Histologically proven recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix that is not amenable to curative treatment with surgery and/or radiation therapy AND has failed 2 previous treatment regimens.

Exclusion Criteria:

• Had/have the following prior/concurrent therapy:

  • Systemic corticosteroids (oral or injectable) within 7 days of first dose of 852A (topical or inhaled steroids are allowed)
  • Investigational drugs/agents within 14 days of first dose of 852A
  • Immunosuppressive therapy, including cytotoxic agents within 14 days of first dose of 852A (nitrosoureas within 30 days of first dose)
  • Drugs known to induce QT interval prolongation and/or induce Torsades de pointes unless best available drug required to treat life-threatening conditions
  • Radiotherapy within 3 weeks of the first dose of 852A
  • Hematopoietic cell transplantation within 4 weeks of first dose of 852A
  • Evidence of active infection within 3 days of first dose of 852A
  • Active fungal infection or pulmonary infiltrates (prior treated disease stable for 2 weeks is allowable)
  • Cardiac ischemia, cardiac arrhythmias or congestive heart failure uncontrolled by medication
  • History of, or clinical evidence of, a condition which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk
  • Uncontrolled intercurrent or chronic illness
  • Active autoimmune disease requiring immunosuppressive therapy within 30 days
  • Active coagulation disorder not controlled with medication
  • Pregnant or lactating
  • Concurrent malignancy (if in remission, at least 5 years disease free) except for localized (in-situ) disease, basal carcinomas and cutaneous squamous cell carcinomas that have been adequately treated
  • Any history of brain metastases or any other active central nervous system (CNS) disease

Contacts and Locations

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Locations

United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Pfizer

Investigators

Principal Investigator:	Sarah Cooley, MD	Masonic Cancer Center, University of Minnesota
Principal Investigator:	Melissa A. Geller, MD	Masonic Cancer Center, University of Minnesota

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Melissa Geller, M.D., Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:	NCT00319748 History of Changes
Obsolete Identifiers:	NCT00363493
Other Study ID Numbers:	06US03IMP-852A; MT2006-02 ( Other Identifier: Blood and Bone Marrow Transplantation Program ); 2006LS005 ( Other Identifier: Masonic Cancer Center, University of Minnesota )
First Posted:	April 27, 2006
Results First Posted:	September 25, 2009
Last Update Posted:	December 28, 2017
Last Verified:	December 2017

Keywords provided by Masonic Cancer Center, University of Minnesota:

Breast; Ovarian; Endometrial; Cervical; Metastatic; 852A	IRM; Oncology; Metastatic Cervical Cancer; Metastatic Ovarian Cancer; Metastatic Breast Cancer; Metastatic Endometrial Cancer

Additional relevant MeSH terms:

Ovarian Neoplasms; Uterine Cervical Neoplasms; Endometrial Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases	Genital Diseases, Female; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Cervical Diseases; Uterine Diseases