A Dose Escalation, Safety and Activity Study of CDX-014 in Patients With Renal Cell Carcinoma and Ovarian Clear Cell Carcinoma

Metastatic Renal Cell Carcinoma Clinical Trial

Official title:

A Phase l Open-Label, Dose Escalation and Cohort Expansion Study, to Assess the Safety and Activity of the Antibody-Drug Conjugate CDX-014 in Advanced or Metastatic Renal Cell Carcinoma (RCC) and Advanced or Metastatic Ovarian Clear Cell Carcinoma (OCCC)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02837991
• Other study ID #: CDX014-01
• Status: Terminated
• Phase: Phase 1
• Start date: June 2016
• Est. completion date: November 16, 2018

Study information

• Verified date: November 2018
• Source: Celldex Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a study to determine the safety of CDX-014 and effectiveness (how well the drug works).

Description:

CDX-014 is an antibody-drug conjugate that binds to a protein called TIM-1, which is found on a high percentage of kidney cells that are clear or papillary and ovarian cancer cells that are clear cell.

The study will enroll patients with advanced or metastatic renal cell carcinoma and ovarian clear cell carcinoma to determine the safety and efficacy of CDX-014.

This study will include a Dose-Escalation Phase followed by a Cohort Expansion Phase

All patients enrolled in the study will be closely monitored to determine if there is a response to the treatment as well as for any side effects that may occur.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: November 16, 2018
• Est. primary completion date: November 16, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologically confirmed diagnosis of advanced or metastatic clear cell or papillary renal cell carcinoma or histologically confirmed clear cell ovarian carcinoma.

2. For RCC, at least two prior anticancer regimens (one must be a VEGF-targeted TKI), or are otherwise inappropriate candidates for all approved therapies. For OCCC, at least one line of prior therapy with a platinum and taxane regimen.

3. Documented progressive disease based on radiographic, clinical or pathologic assessment during or subsequent to last therapy.

4. Measureable (target) disease.

5. Must have available tumor tissue for TIM-1 expression testing

6. Life expectancy = 3 months

7. If of childbearing potential (male or female), agrees to use effective contraception during study treatment and for at least 6 months following last treatment dose.

Exclusion Criteria:

1. Prior therapy containing MMAE

2. Any prior cytotoxic chemotherapy regimen, including antibody drug conjugates for RCC or cytotoxic chemotherapy within 3 weeks of study treatment for OCCC

3. Tyrosine kinase inhibitor (TKI) therapy within 2 weeks or at least 5 half-lives (whichever is longer) prior to planned start of study treatment.

4. Monoclonal antibody therapy within 4 weeks prior to the planned start of study treatment.

5. Radiation therapy within 4 weeks prior to start of study treatment (palliative radiotherapy to bone lesions allowed up to 2 weeks prior to study treatment start).

6. Major surgery or significant traumatic injury within 4 weeks prior to study entry.

7. Use of other investigational drugs within 2 weeks or 5 half-lives (whichever is longer) prior to study treatment.

8. Concurrent severe and/or uncontrolled medical conditions (uncontrolled diabetes or infection), known infection with HIV, Hepatitis B or Hepatitis C.

9. Brain metastases, unless previously treated and asymptomatic and not progressive for 2 months.

10. Significant cardiovascular disease (including congestive heart failure).

11. Other malignancy except for treated and cured basal or squamous cell skin cancer, cured in situ cancers, or other cancer from which the patient has been disease-free for = 3 years.

12. Active systemic infection requiring treatment. Infection controlled by oral therapy will not be exclusionary.

13. Chronic use of systemic corticosteroid above an accepted physiologic dose (5mg per day of prednisone or equivalent) within 7 days of enrollment except when used as premedication

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Clear-cell Renal Cell Carcinoma
• Kidney Neoplasms
• Metastatic Renal Cell Carcinoma
• Ovarian Clear Cell Carcinoma
• Papillary Renal Cell Carcinoma
• Renal Cell Carcinoma (RCC)

Intervention

Drug:
• CDX-014

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	HonorHealth Research Institute	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Celldex Therapeutics

Country where clinical trial is conducted

United States, 

References & Publications (1)

McGregor BA, Gordon M, Flippot R, Agarwal N, George S, Quinn DI, Rogalski M, Hawthorne T, Keler T, Choueiri TK. Safety and efficacy of CDX-014, an antibody-drug conjugate directed against T cell immunoglobulin mucin-1 in advanced renal cell carcinoma. Inv — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Escalation - Determine Maximum Tolerated Dose (MTD)	Determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of CDX-014 (in mg/kg). MTD will be defined as the highest dose-level where DLT (dose-limiting toxicity) occurs in less than 33% of treated patients.	Within 21 days after first dose.
Primary	Cohort Expansion - Assess Objective Response Rate (ORR)	Objective Response Rate (ORR) defined as the proportion of patients who achieve radiographic partial or complete response according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guideline.	Evaluated every 6-9 weeks following treatment initiation until treatment is discontinued or disease progression, up to 5 years.