Testis CAB: Cabazitaxel as Salvage Treatment for Cisplatin-resistant Germ Cell Cancer

• ClinicalTrials.gov Identifier: NCT02478502
• Recruitment Status: Recruiting
• First Posted: June 23, 2015
• Last Update Posted: July 20, 2022
• Sponsor: University Hospital, Akershus
• Collaborator: Sanofi
• Information provided by (Responsible Party): Jan Oldenburg, University Hospital, Akershus

Study Description

Brief Summary:

Germ cell tumors belong to the most chemosensitive malignancies. Paclitaxel in combination with ifosfamide and cisplatin (TIP) has become a common regimen for salvage treatment of germ cell cancer.

Cabazitaxel may overcome resistance to docetaxel and paclitaxel and might have clinical activity in patients with metastatic and progressive germ cell tumors.

Condition or disease	Intervention/treatment	Phase
Testicular Cancer	Drug: cabazitaxel	Phase 2

Detailed Description:

Patients with metastatic germ cell cancer and relapse after two or more courses of cisplatin-based chemotherapy or after high-dose chemotherapy have a poor prognosis and no curative options. Taxanes in various combinations unfold cytotoxic effects on germ cell tumors resistant to conventional doses of cisplatin. Paclitaxel in combination with ifosfamide and cisplatin (TIP) has become a common regimen for salvage treatment of germ cell cancer. In most patients, however, resistance to paclitaxel, as evidenced by progression occurs.Cabazitaxel has been developed to overcome resistance to docetaxel and paclitaxel. It has shown efficacy in patients progressing during docetaxel therapy in a large phase III trial (TROPIC) in patients with castration-resistant prostate cancer. Furthermore, chemotherapy resistance might be less likely to develop in patients receiving cabazitaxel as compared to other taxanes.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study Cabazitaxel as Salvage Treatment for Cisplatin-resistant Germ Cell
• Study Start Date: June 2015
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: June 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cabazitaxel (single arm study); Cabazitaxel 25 mg/m2 each 3. week (no other drugs will be administered)	Drug: cabazitaxel; cabazitaxel is given to patients with progressive testicular cancer after cisplatin-based chemotherapy; Other Name: Jevtana

Outcome Measures

Primary Outcome Measures :

1. Objective response rate [ Time Frame: after 3 and 6 cycles of cabazitaxel (9 and 18 weeks, respectively) as change from baseline (radiologic evaluation before first cycle of cabazitaxel) ]
   Recist 1.1

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:

• Male patients ≥ 18 years old
• Histologically verified metastatic germ cell cancer (GCC) of the testicle or extragonadal GCC originating from retroperitoneum or mediastinum
• Disease progression during cisplatin-based chemotherapy or Disease progression or relapse after high-dose chemotherapy or Disease progression or relapse after at least 2 different cisplatin-based regimens
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0-2
• Life expectancy ≥ 3 months
• At baseline adequate function of liver, kidneys and bone marrow:

·Neutrophils ≥ 1.5 x 109/L·

• Hemoglobin ≥ 9.0 g/dL
• Platelets ≥ 100 x 109/L
• Creatinine ≤ 1.5 x upper limit of normal (ULN)
• Total Bilirubin ≤ 1.0 x ULN
• Serum glutamate oxaloacetate transaminase (SGOT/AST) ≤ 1.5 x ULN
• Serum glutamate pyruvate transaminase (SGPT/ALT) < 1.5 x ULN

Exclusion Criteria:

• Systemic antitumor treatment within 21 days before study entry
• Simultaneous radiotherapy to the only target lesion
• Patients unwilling or unable to comply with the protocol
• Patients with unstable angina pectoris, myocardial infarction ≤ 6 months prior to first study treatment, congestive heart failure New York Heart Association (NYHA) III-IV or serious uncontrolled cardiac arrhythmias
• Patients with an active or uncontrolled infection
• Patients who have a history of another primary malignancy and are off treatment for ≤ 3 years, with the exception of non-melanoma skin cancer
• Patients who have undergone major surgery within 4 weeks prior to starting study drug (e.g. intra-thoracic, intra-abdominal, or intra-pelvic) or significant traumatic injury, or who have not recovered from the side effects of any of the above within 6 weeks
• Patients who have participated in another interventional clinical trial within 30 days before study entry
• Other serious medical conditions that could impair the ability of the patient to participate in the study
• Active infection requiring systemic antibiotic-, anti-viral-, or anti-fungal medication
• Neuropathy ≥Grade 2 Common Terminology Criteria for Adverse Events (CTCAE)
• Patient with reproductive potential not implementing accepted and effective method of contraception during the whole study period and up to 6 months after the last dose of cabazitaxel

• One or more of the following cabazitaxel-specific requirements:

  • History of severe hypersensitivity reaction (≥ Grade 3) to docetaxel
  • History of severe hypersensitivity reaction (≥ Grade 3) to polysorbate 80 containing drugs
  • Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4 (CYP3A4) (a one week wash-out period is necessary for patients who are already on these treatments) (see Appendix A and B)
  • Concurrent or planned treatment with Organic anion transporting polypeptide1B1 (OATP1B1) substrates e.g. statins, valsartan, repaglinide which have to be taken within 12 hours before cabazitaxel application and 3 hours after the end of infusion, refer table 9

Contacts and Locations

Contacts

Contact: Jan Oldenburg, MD, PhD; 91502900 ext +47; jan.oldenburg@medisin.uio.no

Contact: Lisbeth Johnsen, M.Sc; 45246719 ext +47; lisbeth.johnsen@ahus.no

Locations

Denmark

Rigshospitalet; Recruiting

Copenhagen, Denmark

Contact: Gedske Daugaard, MD, PhD 35453545 ext +45 gedske.daugaard@rh.regionh.dk

Principal Investigator: Gedske Daugaard, MD, PhD

Germany

University Clinic Hamburg Eppendorf; Withdrawn

Hamburg, Germany, 20246

Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T); Active, not recruiting

Meldola, Italy, 47014

Norway

Oslo University Hospital; Recruiting

Oslo, Norway, N-0424

Contact: Helene Negaard, MD, PhD UXHEGA@ous-hf.no

Contact: Marit Husby, MD 23026600 ext +47 UXHUMC@ous-hf.no

Principal Investigator: Helene Negaard, MD, PhD

Sweden

University Hospital of Uppsala, Department of Oncology; Active, not recruiting

Uppsala, Sweden, 75185

Sponsors and Collaborators

University Hospital, Akershus

Sanofi

Investigators

• Principal Investigator: Jan Oldenburg, MD, PhD; University Hospital, Akershus

More Information

• Responsible Party: Jan Oldenburg, MD, PhD, Coordinating Investigator, University Hospital, Akershus
• ClinicalTrials.gov Identifier: NCT02478502
• Other Study ID Numbers: 2012/1627 b; 2012-004418-32 ( EudraCT Number )
• First Posted: June 23, 2015
• Last Update Posted: July 20, 2022
• Last Verified: July 2022

Keywords provided by Jan Oldenburg, University Hospital, Akershus:

testicular cancer; cisplatin resistancy

Additional relevant MeSH terms:

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