Tecemotide (L-BLP25) in Prostate Cancer

• ClinicalTrials.gov Identifier: NCT01496131
• Recruitment Status: Completed
• First Posted: December 21, 2011
• Results First Posted: March 9, 2018
• Last Update Posted: March 9, 2018
• Sponsor: EMD Serono
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): EMD Serono

Study Description

Brief Summary:

This study examines tecemotide (L-BLP25) in combination with standard treatment for prostate cancer.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Radiation: Radiation therapy; Drug: Goserelin; Drug: Cyclophosphamide; Drug: Tecemotide (L-BLP25)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Study of Tecemotide in Combination With Standard Androgen Deprivation Therapy and Radiation Therapy for Untreated, Intermediate and High Risk Prostate Cancer Patients
• Actual Study Start Date: October 24, 2011
• Actual Primary Completion Date: November 25, 2016
• Actual Study Completion Date: November 25, 2016

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Standard therapy; Radiation therapy in combination with androgen deprivation therapy (ADT).	Radiation: Radiation therapy; Radiation therapy will be administered at a daily dose of 180 centigrays (cGy) 5 days a week for approximately 6 to 8 weeks.; Drug: Goserelin; ADT (Goserelin) will be administered at a dose of 10.8 milligrams (mg) subcutaneously every 3 months for 24 months for the high risk group and for 6 months in the intermediate risk group, starting 2-3 months prior to radiation therapy.
Experimental: Standard therapy plus tecemotide (L-BLP25); Standard therapy (radiation therapy in combination with ADT) plus tecemotide (L-BLP25).	Radiation: Radiation therapy; Radiation therapy will be administered at a daily dose of 180 centigrays (cGy) 5 days a week for approximately 6 to 8 weeks.; Drug: Goserelin; ADT (Goserelin) will be administered at a dose of 10.8 milligrams (mg) subcutaneously every 3 months for 24 months for the high risk group and for 6 months in the intermediate risk group, starting 2-3 months prior to radiation therapy.; Drug: Cyclophosphamide; Cyclophosphamide will be administered at a single dose of 300 milligrams per square meter (mg/m^2) to a maximum of 600 mg, as an intravenous injection 3 days prior to the first administration of tecemotide (L-BLP25).; Drug: Tecemotide (L-BLP25); Tecemotide (L-BLP25) will be administered at a dose of 918 microgram (mcg) as subcutaneous injection every 2 weeks for 5 doses followed by every 6 weeks for an additional 4 doses, starting 2-3 months prior to radiation therapy and on the same day that ADT began.; Other Names: L-BLP25; BLP25 liposome vaccine; Epipepimut-S

Outcome Measures

Primary Outcome Measures :

1. Number of Subjects With Change From Baseline in the Mucinous Glycoprotein 1 (MUC1) Specific Systemic T-Cells Immune Response at Day 60 (Pre-Radiation) [ Time Frame: Baseline and Day 60 (Pre-Radiation) ]
   MUC1-specific systemic immune response was measured by intracellular cytokine antigen specific staining following a period of in vitro stimulation (IVS) with overlapping 15-mer peptide pools encoding the tumor-associated antigen (TAA) MUC-1. Baseline was defined as the measurement taken prior to the first dose of study medication (Day 1).
2. Number of Subjects With Change From Baseline in the Mucinous Glycoprotein 1 (MUC1) Specific Systemic T-Cells Immune Response at Day 190 (Post-radiation) [ Time Frame: Baseline and Day 190 (Post-radiation) ]
   MUC1-specific systemic immune response was measured by intracellular cytokine antigen specific staining following a period of in vitro stimulation (IVS) with overlapping 15-mer peptide pools encoding the tumor-associated antigen (TAA) MUC-1. Baseline was defined as the measurement taken prior to the first dose of study medication (Day 1).

Secondary Outcome Measures :

1. Number of Subjects With Progression/Recurrence Status Based on Prostate-specific Antigen (PSA) Levels [ Time Frame: From randomization up to 24 months ]
   Progression/recurrence status was reported based on Prostate-specific Antigen (PSA) Levels. Recurrence of PSA after completion of therapy represents disease progression and was determined using the American Society for Therapeutic Radiology and Oncology (ASTRO) "Phoenix criteria". These criteria define biochemical recurrence after radiation therapy as a PSA level equal to the lowest (nadir) PSA level achieved after therapy plus 2 nanogram per milliliter.
2. Number of Subjects With a Doubling in Number of T-cells in Tumor Biopsy From Baseline at Pre-radiotherapy (Pre-RT) and Post-radiotherapy (Post-RT) [ Time Frame: Baseline, Week 6-12 (Pre-RT), Week 40 (Post-RT) ]
   Doubling in number of T-cells was assessed by immunologic responses (in the tumor microenvironment) in subjects consenting to undergo study biopsies. Baseline was defined as the measurement taken within 8 weeks of prior to the first dose of study medication (Day 1).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histopathologic documentation of prostate cancer confirmed at the institution of study enrollment prior to starting this study
• Newly diagnosed or previously untreated prostate cancer with intermediate or high risk features as defined in the protocol
• No evidence of metastatic disease on computed tomography (CT) / magnetic resonance imaging (MRI) or bone scans
• No systemic steroid use within 2 weeks prior to initiation of experimental therapy. Limited doses of systemic steroids to prevent intravenous contrast, allergic reaction or anaphylaxis (in subjects who have known contrast allergies) are allowed
• Eastern Co-operative Oncology Group (ECOG) performance status of 0-1
• Human leukocyte antigen (HLA)-A2 or A3 positive for immunologic monitoring
• Hematological and biochemical eligibility parameters as defined in the protocol
• No other active malignancies within the past 3 years (with the exception of non-melanoma skin cancers or carcinoma in situ of the bladder)
• Willing to travel to the study center(s) for follow-up visits
• Age greater than or equal to 18 years old
• Able to understand and sign informed consent
• Must agree to use effective birth control (such as a condom) or abstinence during and for a period of 4 months after the last administration of immunotherapy

Exclusion Criteria:

• No evidence of being immunocompromised by human immunodeficiency virus, a medical condition requiring systemic steroids, a medical condition requiring immunosuppressive therapy, splenectomy
• Active Hepatitis B or Hepatitis C
• Subjects should have no autoimmune diseases that have required treatment as specified in the protocol
• History of immunodeficiency diseases, hereditary or congenital immunodeficiencies
• Serious intercurrent medical illness
• A clinically significant cardiac disease
• Subjects who have received any prior therapy for prostate cancer
• Subjects who have known brain metastasis, or with a history of seizures, encephalitis, or multiple sclerosis
• Subjects receiving any other investigational agents
• Contraindication to biopsy such as bleeding disorders, ratio of prothrombin time to partial thromboplastin time (PT/PTT) >=1.5 times the upper limit of normal, artificial heart valve
• Contraindication to MRI such as subjects weighing >136 kilograms, allergy to magnetic resonance (MR) contrast agent, subjects with pacemakers, cerebral aneurysm clips, shrapnel injury or implantable electronic devices
• Contraindication to radiation therapy such as pre-existing and active prostatitis or proctitis, inflammatory bowel disease or known genetic sensitivity to ionizing radiation, or history of prior radiation to the pelvis

Contacts and Locations

Locations

United States, Massachusetts

Please Contact US Medical Information

Rockland, Massachusetts, United States

Sponsors and Collaborators

EMD Serono

National Cancer Institute (NCI)

Investigators

• Study Director: Medical Responsible; EMD Serono, an affiliate of MerckKGaA, Darmstadt, Germany

More Information

• Responsible Party: EMD Serono
• ClinicalTrials.gov Identifier: NCT01496131
• Other Study ID Numbers: EMR 63325-015; BB-IND 7787 ( Other Identifier: CBER )
• First Posted: December 21, 2011
• Results First Posted: March 9, 2018
• Last Update Posted: March 9, 2018
• Last Verified: February 2018

Keywords provided by EMD Serono:

Tecemotide; Prostate Cancer; Goserelin; Cyclophosphamide; Radiotherapy

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Cyclophosphamide; Goserelin; Immunologic Factors; Physiological Effects of Drugs; Immunosuppressive Agents; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Antineoplastic Agents, Hormonal