Phase II Study of Sipuleucel-T and Indoximod for Patients With Refractory Metastatic Prostate Cancer

NCT01560923 | Completed Phase 2 Results DMC

• 1 other identifier: 2011LS109
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 4

Brief Summary

This is a randomized, double blind, multi-institutional phase II therapeutic study of Indoximod or placebo after the completion of standard of care sipuleucel-T (Provenge®) in men with asymptomatic or minimally symptomatic metastatic prostate cancer that is castration resistant (hormone refractory). Patients are randomized to receive either twice daily oral Indoximod or placebo for 6 months beginning the day after the third and final sipuleucel-T infusion.

Conditions

Metastatic Prostate Cancer

Keywords

hormone refractory prostate cancer

Outcome Measures

Primary Outcomes (1)

• Immune Response to Sipuleucel-T

  Assess the augmentation of immune response (PA2024) to sipuleucel-T measured at 14 weeks from first leukapheresis, in response to twice daily oral Indoximod at a dose of 1200 mg/day or an identical looking placebo. The frequency of antigen specific, cytokine producing cells will be determined by an ELISPOT assay. ELISPOT assay will use whole PBMC to assess interferon gamma production in response to the immunizing protein PA2024. Increase in number of ELISPOT responses to PBMC in patients in the treatment arm will be compared to those in control arm.

  14 Weeks from First Leukapheresis

Secondary Outcomes (5)

• Number of Participants With Progression Free Survival at 6 Months

  6 Months

• Objective Response Rate

  4 weeks

• Overall Survival

  2 years

• Quality of Life Scale Results

  6 Months

• Ratio of Antibodies to PA2024

  14 Weeks from First Leukapheresis

Study Arms (2)

Sipuleucel-T + Oral Indoximod

EXPERIMENTAL

Oral Indoximod will be self-administered by mouth twice daily (1200 mg) for 6 months starting after the last (3rd) infusion of sipuleucel-T. Indoximod is a sterile tan powder compounded in capsule form of 200 mg.

Biological: Indoximod; Biological: Sipuleucel-T

Sipuleucel-T + Placebo

PLACEBO COMPARATOR

Placebo is identical-looking to Indoximod and provided in the same manner.

Biological: Sipuleucel-T; Other: Placebo

Interventions

Indoximod BIOLOGICAL

Given twice daily (1200 mg total) by mouth for 6 months.

Also known as: 1-methyl-D-tryptophan

Sipuleucel-T + Oral Indoximod

Sipuleucel-T BIOLOGICAL

Sipuleucel-T will be administered as standard of care. Given by infusion over 60 minutes at Week 0, 2 and 4. Patients will undergo leukapheresis at weeks 0, 2, and 4 with sipuleucel-T infused 3 days later (i.e. Monday/Thursday; Tuesday/Friday).

Also known as: Provenge

Sipuleucel-T + Oral Indoximod; Sipuleucel-T + Placebo

Placebo OTHER

Given in same manner as Indoximod; 1200 mg per day by mouth.

Sipuleucel-T + Placebo

Eligibility Criteria

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

You may qualify if:

• Histologically documented adenocarcinoma of the prostate with metastatic disease as evidenced by soft tissue and/or bony metastases on baseline computed tomography (CT) scan of the abdomen and pelvis and/or bone scan
• Castration-resistant based on a current or historical evidence of disease progression despite surgical or medical castration as demonstrated by one or more of the following:
• PSA progression (defined as two consecutive prostate specific antigen (PSA) measurements at least 14 days apart ≥ 2.0 ng/ml and ≥ 50% above the minimum PSA during castration therapy or above pre-treatment value if no response)
• progression of measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) criteria (≥ 50% increase in the sum of the cross products of all measurable lesions or the development of any new lesions
• progression of non-measureable disease
• Serum PSA ≥ 2.0 ng/ml at study enrollment
• Castration levels of testosterone defined as ≤ 30 ng/dL at study enrollment. Must be at least 3 months from surgical castration or must have received medical castration therapy for at least 3 months and be receiving such therapy at the time of confirmed disease progression
• Asymptomatic or minimally symptomatic disease as demonstrated by Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 and no need for opiate pain medications to control pain/symptoms
• Age 18 years and old
• Adequate bone marrow, renal and hepatic function within 14 days of study enrollment defined as:
• Bone marrow: WBC \> 3,000/uL; absolute neutrophil count \> 1,500/uL; platelets \> 100,000/uL
• Renal: creatinine within institutional upper limit of normal (ULN) OR creatinine clearance \> 60 mL/min/1.73 m2 for patients with creatinine levels above ULN
• Hepatic: total bilirubin \< 1.5 X institutional ULN; aspartate aminotransferase (AST ((SGOT)) and alanine aminotransferase (ALT((SGPT)) \< 2.5 X institutional ULN

You may not qualify if:

• Chronic steroid dependence (should stop all steroid supplementation 4 weeks prior to enrollment)
• Human immunodeficiency virus (HIV)-positive patients and those with other acquired/inherited immunodeficiency
• History of gastrointestinal disease causing malabsorption or obstruction such as, but not limited to Crohn's disease, celiac sprue, tropical sprue, bacterial overgrowth/blind loop syndrome, gastric bypass surgery, strictures, adhesions, achalasia, bowel obstruction, or extensive small bowel resection
• Inability to take medications by mouth
• History of allergic reactions attributed to compounds of similar chemical or biologic composition
• Active autoimmune disease, chronic inflammatory condition, conditions requiring concurrent use of any systemic immunosuppressants or steroids. Mild-intermittent asthma requiring only occasional beta-agonist inhaler use or mild localized eczema will not be excluded.
• Previous allo-transplant of any kind
• History of prior treatment with anti-CTLA4 blocking antibody

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (4)

University of Illinois Medical Center

Chicago, Illinois, 60612, United States

Location

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

New York Presbyterian/Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

1-methyltryptophan; sipuleucel-T

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Dr.Gautam Jha
• Organization: Masonic Cancer Center, University of Minnesota

jhaxx014@umn.edu

612-624-5373

Study Officials

• Shilpa Gupta, M.D.

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2012
• First Posted: March 22, 2012
• Study Start: October 1, 2012
• Primary Completion: December 12, 2018
• Study Completion: December 12, 2018
• Last Updated: April 3, 2020
• Results First Posted: April 3, 2020

Record last verified: 2020-03

Locations

US (4)