Docetaxel/Prednisone Plus Fractionated 177Lu- J591 Antibody for Metastatic, Castrate-resistant Prostate Cancer

A Phase I Trial of Docetaxel/Prednisone Plus Fractionated 177Lu- J591 Anti-prostate-specific Membrane Antigen Monoclonal Antibody in Patients With Metastatic, Castrate-resistant Prostate Cancer

The purpose of this study is to test the effectiveness of the experimental drug, 177Lu-J591 antibody in combination with docetaxel chemotherapy against metastatic, castrate-resistant prostate cancer.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Prednisone; Drug: 177Lu-J591; Drug: 177Lu-J591; Drug: 177Lu-J591; Drug: 177Lu-J591; Drug: 177Lu-J591

Detailed Description

This research is being done because the standard treatments for metastatic prostate cancer that is growing despite medical or surgical therapies are not curative. Existing treatments, such as the docetaxel used as part of this study, may work temporarily, but unfortunately the cancer continues to grow. This test drug, 177Lu-J591, is designed to seek out prostate cancer cells and deliver a lethal dose of radiation to the areas of cancer, but not to normal areas. Some of the normal organs (liver, kidney and bone marrow) do receive some radiation dose that is within the acceptable limits.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina Chapel Hill Lineberger Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologic diagnosis of prostate adenocarcinoma.
• Patient must have progressive metastatic prostate cancer despite adequate medical or surgical castration therapy.
• Serum testosterone < 50 mg/ml.

• Patients who have previously received docetaxel must meet BOTH of the the following criteria:

  • reason for docetaxel discontinuation must NOT have been progression of disease while receiving drug (i.e. progression of cancer must have been AFTER docetaxel discontinuation) AND
  • All docetaxel-related toxicities must have resolved to < grade 1 (with the exception of alopecia) and the pt must be eligible by other criteria

Exclusion Criteria:

• Use of red blood cell or platelet transfusions within 4 weeks of treatment.
• Use of hematopoietic growth factors within 4 weeks of treatment.-Prior cytotoxic chemotherapy and/or radiation therapy within 4 weeks of treatment.
• Bone scan demonstrating confluent lesions involving both axial and appendicular skeleton ("superscan").
• Prior radiation therapy encompassing >25% of skeleton.Prior treatment with 89Strontium or 153Samarium containing compounds (e.g. Metastron®, Quadramet®).
• Platelet count <150,000/mm3.
• Absolute neutrophil count (ANC) <2,000/mm3.
• Hematocrit <30 percent or Hemoglobin < 10 g/dL.
• Abnormal coagulation profile (PT or INR, PTT) > 1.3 x upper limit of normal (unless on therapeutic anticoagulation).
• -Serum creatinine >2.5 mg/dL.
• AST (SGOT) >2.5x ULN.
• Bilirubin (total) >1.5x ULN.
• Serum calcium >11 mg/dL.
• Active serious infection.
• Active angina pectoris or New York Heart Association Class III-IV.
• ECOG Performance Status >2.
• Life expectancy <6 months.
• Deep vein thrombosis and/or pulmonary embolus within 1 month of study entry.
• Other serious illness(es) which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study.
• Prior anti-PSMA monoclonal antibody therapy with the exception of ProstaScint®.
• Prior investigational therapy within 6 weeks of treatment.
• Known history of HIV.
• Known history of myelodysplastic syndrome or leukemia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level 1; 177Lu-J591 at 20 mCi/dose	Drug: Docetaxel; 75 mg/m2 by intravenous infusion over one hour on day 1 of a 21 day cycle.; Other Names: Taxotere; Drug: Prednisone; 10 mg per day starting on cycle 1, day 1; Other Names: Meticorten, Sterapred, Sterapred DS; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 20 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 25 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 30 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 35 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 40 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.
Experimental: Dose Level 2; 177Lu-J591 at 25 mCi/dose	Drug: Docetaxel; 75 mg/m2 by intravenous infusion over one hour on day 1 of a 21 day cycle.; Other Names: Taxotere; Drug: Prednisone; 10 mg per day starting on cycle 1, day 1; Other Names: Meticorten, Sterapred, Sterapred DS; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 20 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 25 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 30 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 35 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 40 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.
Experimental: Dose Level 3; 177Lu-J591 at 30 mCi/dose	Drug: Docetaxel; 75 mg/m2 by intravenous infusion over one hour on day 1 of a 21 day cycle.; Other Names: Taxotere; Drug: Prednisone; 10 mg per day starting on cycle 1, day 1; Other Names: Meticorten, Sterapred, Sterapred DS; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 20 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 25 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 30 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 35 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 40 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.
Experimental: Dose Level 4; 177Lu-J591 at 35 mCi/dose	Drug: Docetaxel; 75 mg/m2 by intravenous infusion over one hour on day 1 of a 21 day cycle.; Other Names: Taxotere; Drug: Prednisone; 10 mg per day starting on cycle 1, day 1; Other Names: Meticorten, Sterapred, Sterapred DS; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 20 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 25 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 30 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 35 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 40 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.
Experimental: Dose Level 5; 177Lu-J591 at 40 mCi/dose	Drug: Docetaxel; 75 mg/m2 by intravenous infusion over one hour on day 1 of a 21 day cycle.; Other Names: Taxotere; Drug: Prednisone; 10 mg per day starting on cycle 1, day 1; Other Names: Meticorten, Sterapred, Sterapred DS; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 20 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 25 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 30 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 35 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.; Drug: 177Lu-J591; Two infusions of 177Lu-DOTA-J591 at 40 mCi/dose will be given. The first infusion will be administered 2-3 days prior to docetaxel cycle 3. The second infusion will be administered two weeks later, i.e., day 13-15 of cycle 3.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determine the maximum tolerated dose of fractionated 177Lu-DOTA-J591 administered concurrently with three-weekly docetaxel for the treatment of patients with metastatic, castrate-resistant prostate cancer.	4 weeks post last J591 dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Determine the toxicity profile of concurrent docetaxel with fractionated 177Lu-DOTA-J591	completion of study treatment

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Investigators: Principal Investigator: Scott Tagawa, M.D., Weill Medical College of Cornell University

Publications and helpful links

General Publications

• Batra JS, Niaz MJ, Whang YE, Sheikh A, Thomas C, Christos P, Vallabhajosula S, Jhanwar YS, Molina AM, Nanus DM, Osborne JR, Bander NH, Tagawa ST. Phase I trial of docetaxel plus lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 (177Lu-J591) for metastatic castration-resistant prostate cancer. Urol Oncol. 2020 Nov;38(11):848.e9-848.e16. doi: 10.1016/j.urolonc.2020.05.028. Epub 2020 Jun 27.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2009
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: June 5, 2009
• First Submitted That Met QC Criteria: June 5, 2009
• First Posted (Estimate): June 9, 2009

Study Record Updates

• Last Update Posted (Actual): May 20, 2021
• Last Update Submitted That Met QC Criteria: May 17, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: CRPC; castrate-resistant prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Docetaxel; Prednisone
• Other Study ID Numbers: 0812010139

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No