Clinical trial NCT02658396: GO-203-2C + Bortezomib For Relapsed Or Refractory MM
Official title: A Phase I Trial of the MUC1 Inhibitor, GO-203-2c, in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Multiple Myeloma
Multiple Myeloma in Relapse
Refractory Multiple Myeloma
Keywords: Multiple Myeloma
Relapsed Multiple Myeloma
Refractory Multiple Myeloma
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Genus Oncology, LLC
name: National Institutes of Health (NIH)
First posted: 2016-01-18
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This research study is studying a combination of targeted therapies known as GO-203-2C and bortezomib as a possible treatment for multiple myeloma that has either progressed or not responded to treatment.

Detailed description: This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved GO-203-2C as a treatment for any disease.

The FDA (the U.S. Food and Drug Administration) has approved bortezomib as a treatment option for your disease.

The purpose of this research study is to test the safety of GO-203-2C with bortezomib. GO-203-2C is a newly discovered compound that binds to an oncoprotein (a cancer causing protein) called MUC1. Myeloma cells harbor an increased amount of MUC1 on its cell surface. By binding to MUC1, GO-203-2C has been shown to cause tumor cell death in laboratory studies.

Bortezomib is an intravenously or subcutaneously administered medication that belongs to a class of drugs called proteasome inhibitors. Proteasome inhibitors disrupt the normal action of cells that breakdown proteins in both normal and cancer cells. This disruption can stall tumor growth and cause cancer cells to die. Bortezomib is currently approved for the treatment of multiple myeloma.

The Investigators want to find the highest dose of GO-203-2C given in combination with bortezomib that can be administered safely without severe or unmanageable side effects.

Eligibility criteria: Inclusion Criteria:

* Participants with multiple myeloma who experienced disease progression after the most recent treatment regimen. Patients must have had prior treatment with a proteasome inhibitor, immunomodulatory drug, and if eligible for transplant an autologous transplant.
* Patients must have measurable disease, defined as 1 or more of the following:

  * serum M-protein \> 0.5 g/dL. For patients with IgA myeloma where the M-protein cannot be quantified on SPEP, total IgA \> 0.5 g/dL.
  * Urine M-protein \> 200mg/24h
  * serum FLC assay: involved FLC level \> 10 mg/dL with abnormal FLC ratio
* Greater than or equal to 18 years in age
* ECOG performance status ≤2 (see Appendix A)
* Life expectancy of greater than 3 months
* Participants must have normal organ and marrow function as defined below:

  * leukocytes ≥2,000/mcL
  * platelets ≥50,000/mcL
  * total bilirubin ≤ 2.0 mg/dL (patients with Gilbert syndrome and Bilirubin ≤ 3.5 mg/dL are eligible)
  * AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
  * creatinine ≤ 2 mg/dL

    --- OR
  * creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
* Women of child-bearing potential must have a documented negative pregnancy test.
* The effects of GO-203-2c on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of GO-203-2c administration.
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Participants who have had chemotherapy or radiotherapy within 14 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 14 days earlier. The use of steroids up the equivalent of 160 mg of dexamethasone is allowed within 14 days of screening, but the last dose has to be given at least 1 day prior to initiation of treatment.
* Participants who are receiving any other investigational agents.
* Uncontrolled hypertension. This is defined as sustained blood pressure elevation \> 140/90 despite antihypertensive therapy. Patients are allowed to start antihypertensive therapy to meet eligibility criteria; however they have to be on a stable antihypertensive regimen for at least 7 days.
* Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant women are excluded from this study because GO-203-2c is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with GO_203-2c, breastfeeding should be discontinued if the mother is treated with GO-203-2c. These potential risks may also apply to other agents used in this study.
* Individuals with a history of a different malignancy are ineligible except for the following circumstances: Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
* Hypersensitivity to bortezomib, boron or mannitol.
* Grade 3 or 4 peripheral neuropathy.
* Prior discontinuation of a bortezomib-based therapy due to toxicity attributed to bortezomib.
* Use of G-CSF administration within 7 days of screening
* Platelet transfusion within 7 days of screening

Primary outcomes:
measure: MTD Dose
timeFrame: Baseline to 21 Days
Secondary outcomes:
measure: Response Rate
timeFrame: 12 Months
measure: Progression Free Survival
timeFrame: Start of treatment to disease progression or death from any cause, assessed up to 100 months
measure: Event Free Survival
timeFrame: Time of treatment initiation to Progressive Disease, death, or nonprotocol therapy, assessed up to 100 months
measure: Time-to-new treatment
timeFrame: From treatment initiation to next treatment or death of any cause, assessed up to 100 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Jacalyn Rosenblatt, MD
role: PRINCIPAL_INVESTIGATOR
References: