Cabozantinib and Abiraterone With Checkpoint Inhibitor Immunotherapy in Metastatic Hormone Sensitive Prostate Cancer (CABIOS Trial)

  • STATUS
    Recruiting
  • End date
    Aug 31, 2025
  • participants needed
    22
  • sponsor
    Washington University School of Medicine
Updated on 14 June 2022

Summary

The goal of this study is to determine the recommended phase 2 dose of the multi-drug combination of abiraterone, cabozantinib, and nivolumab in conjunction with ongoing androgen deprivation therapy in previously untreated metastatic hormone-sensitive prostate cancer patients. The investigators hypothesize that the combination of cabozantinib and abiraterone acetate/prednisone in conjunction with nivolumab will have an acceptable safety profile and will be feasible to administer in patients with hormone-sensitive metastatic prostate cancer.

Details
Condition Metastatic Hormone Refractory Prostate Cancer
Treatment prednisone, Nivolumab, abiraterone acetate, Cabozantinib, Peripheral blood collection
Clinical Study IdentifierNCT04477512
SponsorWashington University School of Medicine
Last Modified on14 June 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Histologically or cytologically confirmed hormone-sensitive prostate adenocarcinoma
Must have evidence of metastatic disease on CT or MRI of the chest, abdomen, and pelvis, or technetium bone scan. May have any type or location of metastases (bone, lymph node, visceral). May have relapsed metastatic disease after initial primary therapy or de novo metastatic disease. Metastatic disease does not have to be confirmed by biopsy
May have been on androgen deprivation therapy (ADT) for metastatic hormone-sensitive prostate cancer for ≤ 12 weeks prior to study enrollment (GnRHR agonist such as leuprolide, goserelin, triptorelin, buserelin, histrelin; GnRHR antagonists such as degarelix, or relugolix). Prior ADT for localized prostate cancer is allowed
Prior palliative radiation therapy for bone metastasis (must be complete ≥14 days prior to enrollment) or any other radiation therapy (must be complete ≥28 days prior to enrollment) is allowed. Prior definitive radiation therapy for localized prostate cancer is allowed
If the patient has undergone bilateral orchiectomy, it must have occurred no more than 12 weeks before study enrollment
Recovery to baseline or ≤ grade 1 from toxicities related to any prior treatments, unless AEs are clinically nonsignificant and/or stable on supportive therapy
At least 18 years of age
ECOG performance status ≤ 1
Normal bone marrow and organ function as defined below
Absolute neutrophil count ≥ 1,500 K/cumm without granulocyte colony-stimulating factor support
White blood cell count ≥ 2,500 K/cumm
Platelets ≥ 100,000 K/cumm without transfusion
Hemoglobin ≥ 9.0 g/DL
Total bilirubin ≤ 1.5 x IULN (for subjects with Gilbert's disease ≤ 3.0 x IULN)
AST(SGOT), ALT(SGPT), and alkaline phosphatase (ALP) ≤ 3.0 x IULN; ALP ≤ 5.0 x IULN with documented bone metastases
Serum creatinine ≤ 2.0 x IULN or calculated creatinine clearance ≥ 30 mL/min by Cockcroft-Gault
Serum albumin ≥ 2.8 g/dL
Urine protein/creatinine ration (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol)), or 24h urine protein ≤1g
PT/INR or PTT < 1.3 x IULN
Castrate testosterone levels with serum testosterone ≤ 50 ng/mL at time of study drug
start, with ongoing ADT throughout the study unless prior bilateral
Ability to understand and willingness to sign an IRB approved written informed consent document (or that of the legally authorized representative, if applicable)
orchiectomy
Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment
Corrected QT interval calculated by the Fridericia formula (QTcF) ≤ 500 ms (by ECG)

Exclusion Criteria

Any evidence of neuroendocrine/small cell prostate cancer, or castrate resistant prostate cancer, as defined by defined by disease progression despite androgen depletion therapy (ADT), either by continuous rise in serum PSA levels as measured over at least 2 consecutive values, or the clinical or radiographic progression of disease, as assessed by the investigator
Prior exposure to second-generation androgen receptor inhibitors (e.g., enzalutamide, apalutamide, darolutamide)
Prior exposure to CYP17 inhibitors (e.g. abiraterone)
No chronic concomitant treatment with strong cytochrome P450 (CYP) 3A4 inducers or inhibitors. If patients are on such agents and these can be safely discontinued, may not have received a strong CYP3A4 inducer/inhibitor within 5 half-lives
Prior systemic chemotherapy for prostate cancer (either for localized or metastatic disease). Patients may have received androgen deprivation therapy (ADT) for < 12 weeks prior to start of study drug; no other cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment
Prior treatment with checkpoint inhibitor or other immunotherapy (e.g., anti-PD-1, anti-PD-L1, anti-CTLA4)
Prior treatment with cabozantinib
Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment
Inability to swallow pills
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohns disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this
criterion
Patients with vitiligo or alopecia
Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
Any chronic skin condition that does not require systemic therapy
Patients without active disease in the last 5 years may be included but only after consultation with the study physician
Patients with celiac disease controlled by diet alone
Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
Currently receiving any other investigational agents
Presence of a condition requiring systemic treatment with either corticosteroids (> 10
Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following
mg daily prednisone equivalent) or other immunosuppressive medications within
Prophylactic use of low-dose aspirin for cardioprotection (per applicable local guidelines) and low-dose low molecular weight heparins (LMWH)
calendar days of start of study treatment. Inhaled or topical steroids and
Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least one week before the first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
adrenal replacement steroid doses < 10 mg daily prednisone equivalent are
permitted in the absence of active autoimmune disease
A history of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib, nivolumab, or abiraterone or other agents used in the study
Uncontrolled, significant intercurrent illness including, but not limited to, the following conditions
Cardiovascular disorders
Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias
Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment
Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within six months before the first dose of study treatment
Patients with known brain metastases or cranial epidural disease unless adequately
Subjects with a diagnosis of incidental, subsegmental PE or DVT within six months are allowed if stable, asymptomatic, and treated with anticoagulation for at least 1 week before the first dose of study treatment
treated with radiotherapy and/or surgery (including radiosurgery) and stable
for at least 4 weeks prior to first dose of study treatment after radiotherapy
The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction
or at least 4 weeks prior to first dose of study treatment after major surgery
Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within six months before the first dose
(e.g., removal or biopsy of brain metastasis). Subjects must have complete
wound healing from major surgery or minor surgery before first dose of study
treatment. Eligible subjects must be neurologically asymptomatic and without
corticosteroid treatment at the time of first dose of study treatment
Lesions invading or encasing any major blood vessels
Other clinically significant disorders that would preclude safe study participation
Serious non-healing wound/ulcer/bone fracture
Uncompensated/symptomatic hypothyroidism
Moderate to severe hepatic impairment (Child-Pugh B or C)
History of organ allograft
Gastrointestinal (GI) disorders, including those associated with a high risk of
perforation or fistula formation
Note: Complete healing of an intra-abdominal abscess must be confirmed before the first
dose
Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5
ml) of red blood, or other history of significant bleeding (e.g., pulmonary
hemorrhage) within 12 weeks before the first dose
Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease
manifestation
Active hepatitis B or C; active HIV. Patients with well-controlled HIV or
hepatitis B or C, or who have had curative treatment for hepatitis C, may be
considered if they meet all other criteria and after discussion with the PI
and drug manufacturers (BMS and Exelixis) using the following criteria for
guidance: <https://www.fda.gov/media/121319/download>
Major surgery (e.g., laparoscopic nephrectomy, GI surgery removal or biopsy
of brain metastasis) within 2 weeks before the first dose of study
treatment. Minor surgeries within 10 days before dose of study treatment
(with the exception of the baseline biopsy, which must have occurred no less
than 6 days prior to the first dose). Subjects must have complete wound
healing from major surgery or minor surgery before first dose of study
treatment. Patients with clinically relevant ongoing complications from
prior surgery are not eligible
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