Microsatellite Stable Relapsed or Refractory Colorectal Cancer Clinical Trial
Official title:
A Phase 2, Open-Label, Randomized, Non-Comparative Study With Preliminary Dose Finding to Evaluate eFT508 Monotherapy or eFT508 in Combination With Avelumab in Subjects With Microsatellite Stable Relapsed or Refractory Colorectal Cancer
| Verified date | July 2019 |
| Source | Effector Therapeutics |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This is a Phase 2, open-label, 2-part, multicenter study in subjects with MSS relapsed/refractory colorectal cancer. The primary objective of Part 1 is to evaluate the safety and tolerability of escalating doses of eFT508 in combination with a fixed dose of avelumab to determine the maximum tolerated dose (MTD) of eFT508 and to select a recommended dose for Part 2. The primary objective of Part 2 is to evaluate antitumor activity of eFT508 at the recommended dose in combination with avelumab or eFT508 monotherapy. Parts 1 and 2 will also evaluate pharmacokinetics (PK) and pharmacodynamics.
| Status | Completed |
| Enrollment | 56 |
| Est. completion date | May 13, 2019 |
| Est. primary completion date | March 26, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - ECOG performance status of 0, 1, or 2 - Pathologically documented diagnosis of colorectal adenocarcinoma. - Progressed on or intolerant of at least 2 prior cancer therapy regimens administered for metastatic disease. - Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer =3 weeks before the start of study therapy. - Part 2 only: Presence of radiographically measurable disease (defined as the presence of =1 lesion that measures =10 mm [=15 mm for lymph nodes]). Measurable disease that was previously radiated is only permitted if progressing. - Agrees to undergo a pretreatment and a post-treatment biopsy. - Microsatellite stable disease determined by IHC and/or polymerase chain reaction (PCR). - Adequate bone marrow function - Adequate hepatic function - Adequate renal function - Normal coagulation profile - Negative antiviral serology - Female subjects of childbearing potential must not be pregnant or breastfeeding - Willingness to use protocol-recommended methods of contraception or to abstain from heterosexual intercourse from start of therapy until at lest 30 days after the last dose of study therapy - Life expectancy of =3 months. Exclusion Criteria: - History of another malignancy except for adequately treated local basal cell or squamous cell carcinoma of the skin; in situ cervical or breast carcinoma; adequately treated, papillary, noninvasive bladder cancer; other adequately treated Stage 1 or 2 cancers currently in complete remission, or any other cancer that has been in complete remission for =2 years. - Known symptomatic brain metastases requiring =10 mg/day of prednisolone (or its equivalent). - Significant cardiovascular disease. - Significant screening ECG abnormalities. - Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. - Known history of colitis, inflammatory bowel disease, pneumonitis, or pulmonary fibrosis. - Ongoing risk for bleeding due to active peptic ulcer disease or bleeding diathesis. - Evidence of an ongoing systemic bacterial, fungal, or viral infection. - Any condition that may impact the subject's ability to swallow oral medications. - Major surgery within 4 weeks before the start of study therapy. - Prior solid organ or bone marrow progenitor cell transplantation. - Prior therapy with any known inhibitor of MNK-1 or MNK-2. - Prior therapy with any of the following: PD-1, PD-L1, CTLA4 antibody, or any other drug targeting T cell checkpoint pathways. - Prior high dose chemotherapy requiring stem cell rescue. - Intolerance to or prior severe (=Grade 3) allergic or anaphylactic reaction to infused antibodies or infused therapeutic proteins. - Vaccination within 4 weeks of the first dose of avelumab and while on study. - Ongoing immunosuppressive therapy. - Use of a strong inhibitor or inducer of cytochrome P450 3A4 (CYP3A4) within 7 days prior to the start of study therapy or expected requirement for use of a strong CYP3A4 inhibitor or inducer during study therapy. - Previously received investigational product in a clinical trial within 30 days or within 5 elimination half lives (whichever is longer) prior to the start of study therapy, or is planning to take part in another clinical trial while participating in this study. - Has any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a subject's ability to sign informed consent, adversely affect the subject's ability to cooperate and participate in the study, or compromise the interpretation of study results |
| Country | Name | City | State |
|---|---|---|---|
| United States | Sarah Cannon Research Institute at HealthONE | Denver | Colorado |
| United States | MD Anderson Cancer Center | Houston | Texas |
| United States | Kansas City Research Institute | Kansas City | Missouri |
| United States | Tennessee Oncology | Nashville | Tennessee |
| United States | Mayo Clinic | Rochester | Minnesota |
| United States | Florida Cancer Specialists | Sarasota | Florida |
| United States | Mayo Clinic | Scottsdale | Arizona |
| Lead Sponsor | Collaborator |
|---|---|
| Effector Therapeutics | Merck KGaA, Darmstadt, Germany, Pfizer |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Part 1: Proportion of subjects with a dose limiting toxicity (DLT) during the first treatment cycle | 28 days | ||
| Primary | Part 2: Overall Response Rate | the proportion of subjects whose best overall response is a complete or partial response | 8-16 weeks |