Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors

NCT02689219 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: IUSCC-0568
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

Brief Summary

This is a Phase II study to evaluate the activity of brentuximab vedotin in relapsed/refractory non-seminomatous germ cell tumors (NSGCT).

Conditions

Germ Cell Tumors; Testis Cancer; Testicular Cancer; Embryonal Carcinoma; Nonseminomatous Germ Cell Tumor

Keywords

Antigens, CD30, Embryonal Germ Cell Tumors

Outcome Measures

Primary Outcomes (1)

• Objective Response (Percent of Patients With Complete Response or Partial Response)

  Measured by RECIST v1.1 and tumor markers (AFP and BhCG). CR - disappearance of all target lesions and normalization of serum tumor markers for at least 4 weeks. When only evidence of disease is elevated serum tumor markers, then values must fall below the upper limit of normal for the assay and remain at that level for at least 4 weeks. PR - at least a 30% decrease in the sum of the diameters of target lesions compared to the baseline sum diameters for at least 2 measurements 1 month apart with the serum markers as stable/decreasing. When only evidence of disease is elevated serum tumor markers, then values must fall \>=90% below baseline pretreatment levels for BhCG or 50% decrease below baseline pretreatment levels for AFP and persist for 6 weeks. If both tumor markers are elevated and one falls below 90% the other should fall at least below 50% of baseline pretreatment levels.The percent of patients with objective response and its 95% exact confidence interval will be provided.

  Up to 1 year

Secondary Outcomes (3)

• Progression Free Survival

  Up to 2 years

• Overall Survival

  Up to 2 years

• Number of Patients With Treatment Related Adverse Events Grade 3 or Above

  Up to 2 years

Study Arms (2)

CD30 positive

EXPERIMENTAL

Brentuximab vedotin, 1.8 mg/kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) will be administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle.

Drug: Brentuximab Vedotin

CD30 negative/unknown

EXPERIMENTAL

Brentuximab vedotin, 1.8 mg/kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) will be administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle.

Drug: Brentuximab Vedotin

Interventions

Brentuximab Vedotin DRUG

Both cohorts will be treated similarly and in parallel but analyzed separately.

Also known as: SGN-35

CD30 negative/unknown; CD30 positive

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years at the time of informed consent.
• Patients with histologically or serologically confirmed relapsed/refractory non-seminoma germ cell tumor, (i.e., embryonal carcinoma, choriocarcinoma, or yolk sac tumors) including female GCT and primary mediastinal NSGCT.
• Patients must have progressed after prior high dose chemotherapy (HDCT) treatment, been deemed not to be a candidate for high dose chemotherapy or refused high-dose chemotherapy, and be considered incurable by other standard therapies including further chemotherapy or surgery. There is no maximum allowable number of previous therapies.
• "Failure" of prior therapy is defined as:
• A \>25% increase in the products of perpendicular diameters of measurable tumor masses during prior therapy which are not amenable to surgical resection.
• The presence of new tumors which are not amenable to surgical resection.
• An increase in AFP or beta-hCG (two separate determinations at least one week apart are required if rising tumor markers are the only evidence of failure).
• NOTE: Patients with clinically growing "teratoma" (normal declining tumor markers and radiographic or clinical progression) should be considered for surgery.
• Patients must have evidence of recurrent or metastatic carcinoma by one or more of the following:
• i) The appearance of metastatic disease by standard imaging techniques ii) The appearance of rising serum tumor marker, AFP or beta-hCG NOTE: If a rising tumor marker is the only evidence of progressive disease, at least 2 consecutive rising values at least one week apart are needed. Patients with only evidence of disease is rising tumor marker AFP and beta-hCG will be provided alternate causes of increased serum levels of these markers are not present, such as cross reaction with luteinizing Hormone (LH) (that can be tested if needed by testosterone suppression of LH), hepatitis, use of marijuana or second primary tumor, etc.
• Patients with primary medistinal non seminomatous germ cell tumor are eligible if they have received first line platinum based chemotherapy and their recurrence is not amenable to surgical resection based on the treating physician expert opinion.
• Patients with late relapse (\>2 years) of non seminomatous germ cell tumors are eligible if they have received first line platinum based chemotherapy and their recurrence is not amenable to surgical resection based on the treating physician expert opinion.
• Patients with brain metastases are allowed onto the study as long as patients have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic. Subjects with neurological symptoms should undergo a head CT scan or brain MRI to exclude brain metastasis, at the discretion of the treating physician.
• Patients with ECOG performance status of 0-2.
• Adequate organ and marrow function as defined below:

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Patients with pure seminoma.
• Patients with pure teratoma.
• Chemotherapy within 2 weeks of initiating study treatment. There is no maximum allowable number of previous therapies.
• Major surgery within 3 weeks of starting study treatment. There is no minimum time requirement for minor procedures such as biopsy or vascular access placement.
• Radiation within 2 weeks of starting study treatment.
• ≥ Grade 3 neuropathy at the time of enrollment.
• Pregnancy or breast-feeding.
• Previous treatment with any anti-CD30 directed therapy.

Sponsors & Collaborators

• Nabil Adra: lead

Study Sites (4)

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Indiana University Health Hospital

Indianapolis, Indiana, 46202, United States

Location

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Neoplasms, Germ Cell and Embryonal; Testicular Neoplasms; Carcinoma, Embryonal; Nonseminomatous germ cell tumor

Interventions

Brentuximab Vedotin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Endocrine System Diseases; Testicular Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Nabil Adra
• Organization: IndianaU

nadra@iu.edu

(317) 944-5349

Study Officials

• Costantine Albany, MD

  Indiana University School of Medicine, Indiana University Simon Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Clinical Medicine

Study Record Dates

• First Submitted: February 12, 2016
• First Posted: February 23, 2016
• Study Start: March 9, 2016
• Primary Completion: November 13, 2018
• Study Completion: January 23, 2019
• Last Updated: December 10, 2019
• Results First Posted: November 26, 2019

Record last verified: 2019-12

Locations

US (4)