Study of Dalantercept and Axitinib in Patients With Advanced Renal Cell Carcinoma
Phase: Phase 2
Diagnosis: Kidney Cancer
NCT ID: NCT01727336
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID:
The purpose of Part 1 of this study is to evaluate the safety and tolerability of dalantercept in combination with axitinib in patients with advanced renal cell carcinoma (RCC) to determine the recommended dose level of dalantercept in combination with axitinib for Part 2. The purpose of Part 2 of this study is to determine whether treatment with dalantercept in combination with axitinib prolongs progression free survival (PFS) compared to axitinib alone in patients with advanced renal cell carcinoma (RCC).
Beth-Israel Deaconess Medical Center
Rupal Bhatt, MD,
Beth Israel Deaconess Medical Center
Beth-Israel Deaconess Medical Center:
Cancer Trials Call Center, 617-667-3060
Key Inclusion Criteria:
- Histologically confirmed, advanced, predominantly clear cell renal cell carcinoma
- Part 1: Progression of disease following up to three lines of prior therapy,
including at least one approved VEGF receptor tyrosine kinase inhibitor for RCC.
Adjuvant therapy is permitted as one line of prior therapy.
- Part 2: Progression of disease following one VEGF receptor TKI for RCC (e.g.
sunitinib, pazopanib, sorafenib, tivozanib, or cabozantinib) inclusive of adjuvant
therapy if there was documented disease progression during treatment. Patients may
have received one additional line of an approved mTOR kinase inhibitor (e.g.
everolimus, temsirolimus). Prior exposure to investigational and/or approved anti
cancer immune therapies is permitted.
- A minimum of 2 weeks since the last dose of prior therapy (a minimum of 4 weeks since
anticancer immune therapy or bevacizumab +/- interferon).
- Measurable disease that is evaluable by Response Evaluation Criteria in Solid Tumors
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy of at least 12 weeks.
- Clinical laboratory values within acceptable ranges within 72 hours prior to study
Key Exclusion Criteria:
- Clinically significant organ/system disease unrelated to RCC that in the judgment of
the investigator should preclude treatment with dalantercept or axitinib.
- Clinically significant cardiovascular risk.
- Known CNS metastases or leptomeningeal disease:
For Part 1, patients with CNS metastases treated with whole brain radiotherapy, gamma
knife, and/or surgery who are considered stable by CNS imaging and are not being treated
with corticosteroids 6 weeks prior to study day 1 may be enrolled.
For Part 2, patients with CNS metastases treated stereotactic radio-surgery (SRS), and/or
surgery who are considered stable by CNS imaging for at least 2 months prior to enrollment
and are not being treated with corticosteroids 6 weeks prior to study day 1 may be
- Any active malignancy, other than RCC, for which chemotherapy or other anti-cancer
therapy is indicated. Patients with adequately treated non-melanoma skin cancer, in
situ cancer, or other cancer from which the subject has been disease-free for at
least 3 years will be permitted.
- Any lesion invading or having encasement ≥ 180 degrees around the wall of a major
blood vessel as assessed by computed tomography (CT) scan and/or magnetic resonance
- Radiotherapy within 2 weeks prior to study day 1.
- Lack of recovery from toxic effects of previous treatment for RCC ≤ grade 1 with the
exception of alopecia, unless stabilized under adequate medical control.
- Patients undergoing renal dialysis.
- Major surgery within 4 weeks prior to study day 1 (patients must have recovered
completely from any previous surgery prior to study day 1).
- Any active infection requiring antibiotic therapy within 2 weeks of study day 1.
- Anti-coagulation therapy (e.g., clopidogrel, dabigatran, warfarin, and heparin).
- Current use of or anticipated inability to avoid potent CTP3A4/5 inhibitors (e.g.,
grapefruit juice, verapamil, ketoconazole, micronazole, itraconazole, erythromycin,
telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir,
lopinavir, atazanavir, amprenavir, fosamprenavir, delavirdine) or CTP3A4/5 inducers
(carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin,
amobarbital, nevirapine, primidone, rifabutin, rifampin, St. John's wort) during
participation in the study.
- Peripheral edema within 2 weeks prior to study day 1.
- Bleeding diathesis including clinically significant platelet disorders or active
hemoptysis (defined as bright red blood of ≥ 1/2 teaspoon [2.5 mL] in any 24 hour
period) within 6 months prior to study day 1. For clinically significant epistaxis
within 4 weeks prior to study day 1, no risk of further bleeding must be clearly
- Known history of hereditary hemorrhagic telangiectasia (HHT).
- Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infections or
positive human immunodeficiency virus (HIV) antibody results. Patients with
sustained virologic response to HCV treatment or immunity to HBV from prior infection
without cirrhosis may be included.
- History of severe (defined as ≥ grade 3, using the National Cancer Institute Common
Toxicity Criteria for Adverse Events, version 4.0 [NCI-CTCAE] v4 current active minor
version) allergic or anaphylactic reaction or hypersensitivity to recombinant
proteins or excipients (10 mM Tris buffered saline) in the investigational agent.
- Any prior treatment with dalantercept or any other agent targeting ALK1 pathway.
- Any prior treatment with axitinib.
- A morbidity (per the prescribing information) that would require starting a patient
at a reduced dose of axitinib.
- Treatment with another investigational drug (with the exception of anticancer immune
therapy) or device, or approved therapy for investigational use, within 5 times the
half-life of the drug or within 3 weeks prior to study day 1 if the half life is not
- Pregnant or lactating female patients.